MDedge Cardiology

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

This transcript has been edited for clarity.

Jorge Plutzky, MD: Hi. I'm Dr Jorge Plutzky, director of preventive cardiology at the Brigham and Women's Hospital, and in that setting I direct our lipid clinic. I'm pleased to be here today to talk about how we communicate about cholesterol. And I'm pleased to be able to do that today with a patient of mine, Brian McMahon.

Brian, thank you for being here. 

Brian McMahon: Thank you, Doctor. 

Plutzky: Why don't you tell people listening how we came to connect in the first place. 

McMahon: Well, it was around statins. I had been prescribed one probably 10 years ago, and I had an adverse reaction to it — a violent reaction. And the doctor just told me to stop taking it. So I did. And I never asked another question.

And then 10 years later, my GP in Connecticut said, "You should go get a calcium score exam. Insurance doesn't cover it. It's 90 bucks, and it'll be the best 90 bucks you ever spent." And then the numbers were not good. That led me to come and talk to you about what do I do now? What are my options? I had an adverse reaction to statins. I didn't think I could even take them. 

Plutzky: That's so important. Really, the failure was in your physician not getting that initial follow-up: Okay, so you had this reaction; what are the potential explanations for that, and what could be the next steps?

It really should not fall upon you as a patient to have to push that. But in fact, when people are better educated about the issues in our system, sometimes you do have to be your own advocate and ask, "What's next?" And it's important for us in communicating these issues during that first encounter, which might be with a primary care physician or a cardiologist, but more often it's with a primary care physician.

We're more motivated when someone's already had an event — secondary prevention. Let's not have another one because the patient has now been through something scary: a heart attack or a stent or even bypass surgery or a stroke. Those really motivate people. But even in that setting, we often find that patients don't necessarily stay on treatment or don't necessarily get treated aggressively enough to the right LDL level.

So that becomes important to set the stage early about why we are doing this, and let's come up with options that are safe, usually well tolerated, and have been extensively studied. 

McMahon: I think the key is that it is a silent killer, so you don't feel bad, you don't have a rash, you don't have a scratch. It's not painful, but it could kill you. But the very fact that it's just that the statin doesn't agree with you — that was a real mess, in my estimation. 

Plutzky: Often in settings of primary prevention, you're trying to conjure up the future for someone, saying, "You know what? If we don't do something, we're going to run into issues." But those patients don't feel bad. You're right that it is silent, but that's where the huge opportunity exists: early intervention — identifying what that risk is and how many different options we have, like if someone doesn't succeed on or has an issue with a statin. We know that's uncommon, but people often do well with some of these other alternatives, including just a different statin, which was the case with you. 

McMahon: Right. And I had no idea that that was even available to me. That was an eye-opener, that there are options available to me, that I can find different things that work; but for goodness' sake, you should be on it. 

Plutzky: Yes, we often have patients do well on a statin. Some patients really can't take a statin.

We'll go through a couple different options. I often will lay out for people who think they're having an issue with the statin that there are three possibilities: One, it's not the statin, because in the clinical trials we see people who quit the placebo as often as they quit the statin. Sharing that with patients matters. It's possible that what one felt wasn't even related to the statin. Two, sometimes reactions are statin specific. We try a different statin and then someone does well. Sometimes that may be influenced by the fact that we've laid out the data and explained to a patient, "We know that statins are safe, effective, and well tolerated, and here's the benefit for you down the road."

Is that part of why that second statin now works? It's hard to know. I've had many physician patients who say, "I didn't feel great on that one, but now I'm on a different statin and I'm feeling, much better." So, everyone reacts differently.

McMahon: I love that you walked me into it too. It wasn't just, "Here's 20 mg. We started at 5 mg, then we went to 10 mg, now we're at 20 mg." You took the time to say, "I hear you and I heard what happened to you. So, let's walk into this." I lost 10 years of taking statins, which would have put me in a different place.

Plutzky: The fact is that the first dose of the statin has the biggest impact on reducing your LDL. And then as you titrate it up, which we do all the time — we have with you — the effect on the lowering of LDL is less impactful. That's why it can be a way in with people to say, "Let's start with this low dose." At least they're on something. And people often say, "Wow! I really feel completely fine on this." There are people who either just can't take a statin at all or who, once they're on the statin, aren't getting to a low enough or appropriate LDL number, and it's good to have those alternatives.

One of them is specifically theoretically designed for people who think they've had muscle issues with statin. Your issues were different, but bempedoic acid is an alternative. And even going beyond that, we now have injectable medicines that really are very effective at bringing down LDL.

When people hear injections, they're like, "Oh my gosh, I don't want to take an injection," but explain to people how easy it is to do those injections. It's basically just a pen against your skin. That really reduces their fear and their anxiety. But it's important to realize that we do have many tools for lowering LDL. If someone runs into a problem with the statin that you can't overcome, then it's important to move on. 

So we should recognize how important it is to lower LDL. Realizing how many tools we have allows people to begin working through the process where the objective is: I want to get my LDL down, and if we can do it with a statin, then we're taking advantage of all this data we have about their benefits. But if that turns out not to work for a given patient, even after trying and explaining things, then let's move on. But let's get to that ultimate goal of lowering LDL as one component of risk. 

I think there's nothing more empowering for the person you're dealing with than to share with them what it is that you know; that you know, based upon medical science and clinical trials, what that rationale is, because no one is trying to hurt themselves. If someone comes in who doesn't want to take a statin, it's not because they're trying to have a heart attack. They're not trying to hurt themselves. There's some barrier to what's motivating them, to what's keeping them from this therapy. We just have to better communicate what the goal is and what the basis is for pursuing this, and then finding your way through the woods of saying, "Well, that worked great and we've made it" vs "We've run into something, so let's go on a different path." 

McMahon: I think that to me was the light-bulb moment, which was that experience with statin: Don't take it anymore. And then 10 years go by and now I'm in trouble. And then I find out that there is a wealth of opportunities. There are so many arrows in your quiver — not to make a Cupid joke, but there are so many arrows available to fix this, and I didn't know it. Now I do.

Plutzky: Yes, it's empowering. I think there's a challenge for us as caregivers to more broadly share what we know so that people are motivated and empowered to say, "I want to get treated. I want to do better. And I understand the extent to which this is a risk for me if I don't do better."

McMahon: Right.

Plutzky: So often there's a family history associated with that, too. Sometimes when I'm communicating with patients the idea of "You need to do this," especially patients with young kids, I'm communicating, "How you eat and your activity level is sending a very powerful message to your kids."

McMahon: Yes. 

Plutzky: We're trying to eat healthy. We're more oriented toward vegetables. We're being active. Let's go for a walk. Let's go for a family run. Let's have a sport that we do together. Or even just the kids seeing you leave the house to say, "I'm off." "Where are you going, Dad?" "I'm going to play tennis." "Can I come with you?" And then…

McMahon: It creates a lifestyle.

Plutzky: Yes. 

McMahon: Well, it comes back to: You have one heart. 

Plutzky: Yes. Well, it's been a pleasure to have a chance to discuss what are really important topics. I mean, this is really impactful. Far beyond just your experience, it's the chance for other people to realize that these are issues that need to be recognized, dealt with; that people need to be empowered; and that ultimately it comes down to us about how to better communicate.

I'm always very focused on how can a patient know what I know and what I think matters based upon evidence, data, clinical trials. How do we share that and share that in very limited time windows? It's been a privilege to work with you, Brian, in a clinical setting, and I'm very appreciative of your taking the time to join us today.

McMahon: Thank you for getting me on the right path. I'm grateful. 

Plutzky: Well, you've done that for yourself. Good talking to you. 

McMahon: Likewise.

Jorge Plutzky, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: Altimmune; Boehringer Ingelheim; Esperion; New Amsterdam; Novo Nordisk

Received research grant from: Boehringer Ingelheim; Novartis

Serve(d) on clinical trial committee for: Esperion; Novo Nordisk

Brian McMahon has disclosed no relevant financial relationships.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?

That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.

“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.

Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” Dr. Cicali said.

Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.

Why PGx Tests Can Have a Big Impact

These tests work by looking for genes that control drug metabolism.

“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”

While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.

Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)

“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”

What the Research Shows

When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.

The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.

When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.

The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.

“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”

Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.

By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:

• In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
• In a 2023  from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
• In a University of Pennsylvania  of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese  of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.

PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.

The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.

Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.

“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”

When, Why, and How to Test

“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.

You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.

Here’s how four PGx experts suggest consumers and physicians approach this option.

Find a Test

More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)

Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.

The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.

For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.

Consider Cost

The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.

In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.

Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.

Understand the Results

As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.

In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.

Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.

Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).

Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.

Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.

Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.

Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.

“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.

Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
 

Little Consensus on Statins for This Age Group

Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.

Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.

Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.

Risk Reduction Seen in Both Senior Groups

Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.

In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.

Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.

One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.

Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”

Numbers Needed to Treat Are Strikingly Low

He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.

The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”

For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”

Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.

He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.

Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.

“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.

“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”

The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.