Cardiology News

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?

Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).

Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
 

Why factor XI?

The hope that factor XI inhibitors will prevent pathologic thrombosis with a lower bleeding risk, compared with other anticoagulants, comes down to the role of factor XI in the coagulation cascade.

In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).

In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.

The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.

John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”

The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.

“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.

“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”

Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”

This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
 

Candidates in development

The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.

Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).

Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”

He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.

Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”

Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.

“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”

While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.

“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.

“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”

Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.

Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
 

Potential indications

The three leading factor XI inhibitors have slightly different phase 3 development programs.

Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.

While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.

Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.

Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”

In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.

Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.

“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”

Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.

“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.

The phase 3 studies are just starting and will take a few years before results are known.
 

Differences between the agents

The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.

“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”

There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.

Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”

Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”

Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
 

What effect could these drugs have?

If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.

“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”

Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”

He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.

But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”

Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”

Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

Moving from one residence to another after an acute myocardial infarction (AMI) significantly increases the risk for death or transition to a long-term care facility as an end-of-life measure, data suggest.

In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.

“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.

The results were published online in the Canadian Journal of Cardiology.
 

Moving and mortality

“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”

The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.

The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.

Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.

The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.

Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.

Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.

“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
 

‘An important marker’

In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.

“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.

The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”

The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

A lack of standardized blood pressure training among doctors, physician assistants, nurses, and other health care professionals is preventing the country’s medical community from curbing hypertension, according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.

First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.

The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.

The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.

The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.

In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.

Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.

The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.

Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.

Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.

Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.

Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.

Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.

A version of this article first appeared on Medscape.com.

Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.

But the nation’s second-largest physician group is cautioning its members not to ask their patients for donations to the clinician’s workplace.

“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.

Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.

In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.

“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.

Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.

Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor. 

Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.

“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”

Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.

“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.

A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.

“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.

Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.

“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.

An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.

A version of this article first appeared on Medscape.com.

Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.

But the nation’s second-largest physician group is cautioning its members not to ask their patients for donations to the clinician’s workplace.

“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.

Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.

In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.

“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.

Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.

Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor. 

Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.

“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”

Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.

“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.

A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.

“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.

Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.

“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.

An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.

A version of this article first appeared on Medscape.com.

Patients sometimes want to give back to their physician or hospital. In recent years, the practice of soliciting donations from these patients has grown into structured fundraising initiatives at some health care organizations. Some employers mandate clinicians solicit donations, while other doctors participate voluntarily.

But the nation’s second-largest physician group is cautioning its members not to ask their patients for donations to the clinician’s workplace.

“In recent decades, more physician practices have become part of large health systems: these arrangements can offer benefits to care but can also lead to interference in the patient-physician relationship and challenges to the physician’s ethical responsibilities to patients,” said Omar T. Atiq, MD, president of the American College of Physicians.

Grateful patient fundraising (GPF) is largely based on models of charitable giving outside of health care and is relatively new to the industry. Simply defined, it is the solicitation of donations by doctors from current and former patients. Funds may be used for operating costs, clinical research, equipment upgrades, or facility improvements.

In a newly published position paper, the ACP, which represents roughly 161,000 physicians, is clear that clinicians should not try to convert their patients into donors.

“Physicians who directly solicit funds from their own patients do risk interfering with the physician-patient relationship, which is supposed to be based on the patient’s best interests, not the physicians’ interests,” said Stacey A. Tovino, JD, PhD, director of health care law programs at the University of Oklahoma, Norman.

Once involved in fundraising, patients may also develop an unrealistic expectation of what kind of care they should receive, according to the ACP.

Another pitfall clinicians may fall into is the HIPAA Privacy Rule. In 2013, HIPAA was expanded to allow hospital fundraisers to access privileged health information, including demographic, health insurance, treating clinician, and data on outcomes. Dr. Atiq said that, since then, electronic health records have been used as tools to aide fundraising efforts. For instance, some health care organizations have embedded a feature inside EHRs to allow physicians to flag development officers when a patient or family member might be a potential donor. 

Patients may be unaware that hospital fundraising departments have access to their electronic health records, or that they have the right to opt out of fundraising solicitations.

“Physicians should not use or reveal patient information for fundraising,” Dr. Atiq said. “Even acknowledging that a person is under one’s care can make it possible for protected health information to be revealed.”

Data-mining EHRs may be legal, Ms. Tovino said, but it hugs a fine ethical line.

“A patient may not expect that their information will be used for these purposes and may not know how to opt out of having their information used in these ways,” Ms. Tovino said.

A clinician’s employment contract, whether it be a full-time position or for specific admitting privileges, may make it hard for them to push back against expectations to ask patients for money or screen for donors. Metrics or expectations to approach potential donors create ethical snares for clinicians – and it pits them between their patient and place of employment.

“GPF does raise ethical concerns, including those surrounding confidentiality and privacy, and whether physicians are being remunerated or evaluated based on their participation,” Ms. Tovino said.

Asked how doctors can avoid being involved in GPF, Dr. Atiq referred to the ACP ethics manual, which separates clinicians from fundraising.

“Redirecting the patient to discuss donations with institutional administrators provides the appropriate venue and firewall,” he said.

An author of the ACP paper reported a paid position on the board of the Government Employees Health Association.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients older than age 70 years have a 23% lower risk of a first major vascular events with each 1 mmol/L lowering of low-density lipoprotein (LDL) cholesterol, which is similar to the benefit seen among younger patients in primary prevention, new research shows.

METHODOLOGY:

• Using various cross-linked Danish registries, researchers analyzed 65,190 participants aged 50 years and older (49,155 aged 50-69 and 16,035 aged 70+) without a history of atherosclerotic cardiovascular disease (ASCVD) who initiated new lipid-lowering treatment and had a baseline LDL cholesterol measurement and a subsequent measurement within a year.
• The primary outcome was hospitalization for a major vascular event, defined as a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization. Secondary outcomes included individual cardiovascular components of the primary outcome and all-cause mortality.

TAKEAWAY:

• During a median follow-up of 2.5 years, 626 older (70 years and over) and 1,123 younger (aged 50-69) participants had a major vascular event, with crude incidence rates of 13.4 and 7.1 per 1000 person-years, respectively.
• After adjustment for potential confounders, each 1-mmol/L reduction in LDL cholesterol in people aged 70 and older was associated with a significant 23% lower risk for major vascular events (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.83), similar to results for those younger than 70 (HR, 0.76; 95% CI, 0.71-0.80; P value for the difference between the age groups, 0.79).
• Results across all cardiovascular secondary analyses supported the main findings, and there was no significant difference between older and younger participants across all subgroup analyses, including using 75 years as the age cutoff.
• There was no association with all-cause mortality for either the older (HR, 1.03; 95% CI, 0.98-1.09) or younger (HR, 1.00; 95% CI, 0.95-1.06) groups.

IN PRACTICE:

“Our results, based on a substantial sample size representative of a contemporary general population, may contribute to informing future guideline recommendations,” and to discussions with older patients about the benefits of LDL lowering therapy, the authors wrote. They stressed that any potential benefits should be balanced against potential harms in this population, as these individuals may have comorbidities and may be taking multiple medications.

In an accompanying editorial, Safi U. Khan, MD, from the department of cardiology at Houston Methodist DeBakey Heart and Vascular Center, said the study “contributes valuable insights regarding the effects of LDL-C-lowering therapy, especially as the burgeoning aging population faces escalating burden of ASCVD,” and added future research “should focus on corroborating these findings and addressing the safety of lipid-lowering treatments in older individuals.”
 

SOURCE:

The study was conducted by Niklas Worm Andersson, MD, department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues. It was published online Journal of the American College of Cardiology.

LIMITATIONS:

The results may not apply to individuals without LDL monitoring when receiving lipid-lowering treatment. Outcomes relied on the validity of recorded diagnostic codes in the registries, and medical record review of cases was not done. Residual confounding can’t be ruled out, in part because data on potentially important risk factors such as smoking, blood pressure, and body mass index weren’t available. The results may not generalize to clinical scenarios or subpopulations not directly studied.

DISCLOSURES:

Dr. Andersson has no relevant conflicts of interest. Author Tine Lovsø Dohlmann, PhD, was employed by Statens Serum Institut during the study, but has been employed by Novo Nordisk since January 2023. All other study authors and the editorialist Dr. Khan have no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study.

If you run into a health care provider these days and ask, “How are you doing?” you’re likely to get a response like this one: “You know, hanging in there.” You smile and move on. But it may be time to go a step further. If you ask that next question – “No, really, how are you doing?” Well, you might need to carve out some time.

It’s been a rough few years for those of us in the health care professions. Our lives, dominated by COVID-related concerns at home, were equally dominated by COVID concerns at work. On the job, there were fewer and fewer of us around as exploitation and COVID-related stressors led doctors, nurses, and others to leave the profession entirely or take early retirement. Even now, I’m not sure we’ve recovered. Staffing in the hospitals is still a huge problem, and the persistence of impersonal meetings via teleconference – which not only prevent any sort of human connection but, audaciously, run from one into another without a break – robs us of even the subtle joy of walking from one hallway to another for 5 minutes of reflection before sitting down to view the next hastily cobbled together PowerPoint.

I’m speaking in generalities, of course.

I’m talking about how bad things are now because, in truth, they’ve never been great. And that may be why health care workers – people with jobs focused on serving others – are nevertheless at substantially increased risk for suicide.

Analyses through the years have shown that physicians tend to have higher rates of death from suicide than the general population. There are reasons for this that may not entirely be because of work-related stress. Doctors’ suicide attempts are more often lethal – we know what is likely to work, after all.

But a focus on physicians fails to acknowledge the much larger population of people who work in health care, are less well-compensated, have less autonomy, and do not hold as respected a position in society. And, according to this paper in JAMA, it is those people who may be suffering most of all.

The study is a nationally representative sample based on the 2008 American Community Survey. Records were linked to the National Death Index through 2019.

Survey respondents were classified into five categories of health care worker, as you can see here. And 1,666,000 non–health care workers served as the control group.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

JAMA

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

The death of a patient comes with many challenges for physicians, including a range of emotional and professional issues. Beyond those concerns, some physicians and their practices must also consider how to collect on any outstanding bill that might go unpaid after a patient’s death.

“When a patient passes away, obviously there is, unfortunately, a lot of paperwork and stress for families, and it’s a very difficult situation,” says Shikha Jain, MD, an oncologist and associate professor of medicine at the University of Illinois at Chicago. “Talking about finances in that moment can be difficult and uncomfortable, and one thing I’d recommend is that the physicians themselves not get involved.”

Instead, Dr. Jain said, someone in the billing department in the practice or the hospital should take a lead on dealing with any outstanding debts.

“That doctor-patient relationship is a very precious relationship, so you don’t want to mix that financial aspect of providing care with the doctor-patient relationship,” Dr. Jain said. “That’s one thing that’s really important.”

The best approach in such situations is for practices to have a standing policy in place that dictates how to handle bills once a patient has died.

In most cases, the executor of the patient’s will must inform all creditors, including doctors, that the decedent has died, but sometimes there’s a delay.
 

Hoping the doctor’s office writes it off

“Even though the person in charge of the estate is supposed to contact the doctor’s office and let them know when a patient has passed, that doesn’t always happen,” says Hope Wen, head of billing at practice management platform Soundry Health. “It can be very challenging to track down that information, and sometimes they’re just crossing their fingers hoping that the doctor’s office will just write off the balance, which they often do.”

Some offices use a service that compares accounts receivable lists to Social Security death files and state records to identify deaths more quickly. Some physicians might also use a debt collection agency or an attorney who has experience collecting decedent debts and dealing with executors and probate courts.

Once the practice becomes aware that a patient has died, it can no longer send communications to the name and address on file, although it can continue to go through the billing process with the insurer for any bills incurred up to the date of the death.

At that point, the estate becomes responsible for the debt, and all communication must go to the executor of the estate (in some states, this might be called a personal representative). The office can reach out to any contacts on file to see if they are able to identify the executor.

“You want to do that in a compassionate way,” says Jack Brown III, JD, MBA, president of Gulf Coast Collection Bureau. “You’ll tell them you’re sorry for their loss, but you’re wondering who is responsible for the estate. Once you’ve identified that person and gotten their letter of administration from the probate court or a power of attorney, then you can speak with that person as if they were the patient.”

The names of executors are also public record and are available through the probate court (sometimes called the surrogate court) in the county where the decedent lived.

“Even if there’s no will or no executive named, the court will appoint an administrator for the estate, which is usually a family member,” said Robert Bernstein, an estate lawyer in Parsippany, N.J. “Their information will be on file in the court.”
 

Insurance coverage

Typically, insurance will pay for treatment (after deductibles and copays) up until the date of the patient’s death. But, of course, it can take months for some insurance companies to make their final payments, allowing physicians to know exactly how much they’re owed by that estate. In such cases, it’s important for physicians to know the rules in the decedent’s state for how long they have to file a claim.

Most states require that claims occur within 6-9 months of the person’s death. However, in some states, claimants can continue to file for much longer if the estate has not yet paid out all of its assets.

“Sometimes there is real estate to sell or a business to wind down, and it can take years for the estate to distribute all of the assets,” Mr. Bernstein says. “If it’s a year later and they still haven’t distributed the assets, the physician can still file the claim and should be paid.”

In some cases, especially if the decedent received compassionate, quality care, their family will want to make good on any outstanding debts to the health care providers who took care of their loved ones in their final days. In other cases, especially when a family member has had a long illness, their assets have been depleted over time or were transferred to other family members so that there is little left in the estate itself when the patient dies.

Regardless of other circumstances, the estate alone is responsible for such payments, and family members, including spouses and children, typically have no liability. (Though rarely enforced, some states do have filial responsibility laws that could hold children responsible for their parents’ debts, including unpaid medical bills. In addition, states with community property laws might require a surviving spouse to cover their partner’s debt, even after death.)

The probate process varies from state to state, but in general, the probate system and the executor will gather all existing assets and then notify all creditors about how to submit a claim. Typically, the claim will need to include information about how much is owed and documentation, such as bills and an explanation of benefits to back up the claim. It should be borne in mind that even those who’ve passed away have privacy protections under the Health Insurance Portability and Accountability Act, so practices must be careful as to how much information they’re sharing through their claim.

Once the estate has received all the claims, the executor will follow a priority of claims, starting with secured creditors. Typically, medical bills, especially those incurred in the last 90 days of the decedent’s life, have priority in the probate process, Mr. Brown says.
 

How to minimize losses

In that case, the practice would write off the unpaid debt as a business loss. If there are not enough assets in the estate to pay all claims, the executor will follow a state schedule that apportions those assets that are available.

There are some steps that practices can take to protect themselves from incurring such losses. For example, before beginning treatment, practices might consider asking patients to name a guarantor, who will essentially promise to cover any outstanding debts that the patient incurs.

To be binding, the office will need a signature from both the patient and the guarantor. Some offices may also keep a patient credit card number on file with written authorization that they can use to pay bills that are past due, although this payment method would no longer be valid after a patient dies.

While it’s important for all physicians to document and verify the financial information for their patients, oncologists often must consider an additional layer of fiduciary responsibility when it comes to their patients. Ms. Wen suggests that oncology offices check in with insurance companies to determine whether a patient has exhausted their benefits.

“That can happen with cancer patients, depending on how long they’ve been receiving treatment and what type of treatment they’ve been getting,” she said. “Some of the clinical trials, insurance will pay for them, but they’re really expensive and can get toward that max. So knowing where they are with their insurance coverage is big.”

When time is of the essence, some patients will choose to go forward with a treatment before receiving insurance approval. In those cases, the office must have an additional conversation in which the costs of the treatment are discussed. The office should obtain written confirmation of who will pay if the insurer does not, Ms. Wen said. While it’s the patient’s responsibility to keep track of their insurance benefits, oncology practices and hospitals must also exercise due diligence in monitoring the benefits that are available.

“That’s part of their contract with insurance companies if they’re in network, helping patients understand their benefits,” Ms. Wen saids.

It’s also important for practices to keep clear, consistent records to make it easier to identify outstanding bills and the correct contact information for them. If bills had gone unpaid prior to a patient’s death and the office started legal action and received a judgment, that claim would typically go ahead of other creditors’ claims.

Dr. Jain says that some practices might also consider keeping a financial adviser or social worker on staff who can assist patients and their families with understanding their out-of-pocket costs for treatment.

“Financial toxicity in oncology and medical care is a very real problem,” she says. “At the beginning of the relationship, I recommend that my patients get set up with a financial specialist that can help them navigate that aspect, not only when a patient passes away but during the process of receiving treatment, so they’re not shocked by the bills.”

A version of this article first appeared on Medscape.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

People with long COVID have specific biomarkers in their blood, according to results of a study published in Nature. 

The findings may be a step toward creating blood tests to positively identify people with long COVID so specialized treatments can be employed, researchers said.

 “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID,” said David Putrino, PhD., lead author and professor of rehabilitation and human performance and director of the Abilities Research Center at Icahn Mount Sinai Health System, New York.

Researchers from the Icahn School of Medicine at Mount Sinai and Yale School of Medicine looked at blood samples from about 270 people between January 2021 and June 2022. The people had never been infected with COVID, had fully recovered from an infection, or still showed symptoms at least four months after infection.

Using machine learning, the research teams were able to differentiate between people with and without long COVID with 96% accuracy based on distinctive features in the blood samples, according to a news release from Mount Sinai.

People with long COVID had abnormal T-cell activity and low levels of the hormone cortisol. Cortisol helps people feel alert and awake, which would explain why people with long COVID often report fatigue, NBC News said in a report on the study.

“It was one of the findings that most definitively separated the folks with long Covid from the people without long Covid,” Dr. Putrino told NBC News.

The study also found that long COVID appears to reactivate latent viruses including Epstein-Barr and mononucleosis, the study said.

The blood tests could allow doctors to come up with specialized treatments in people who report a wide variety of long COVID symptoms, Dr. Putrino said. 

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” he said.

The Centers for Disease Control and Prevention says about one in five Americans who had COVID still have long COVID. Symptoms include fatigue, brain fog, dizziness, digestive problems, and loss of smell and taste.

A version of this article appeared on WebMD.com.

The second patient to be transplanted with a genetically modified pig heart at the University of Maryland Medical Center (UMMC), Baltimore, is said to be stable and doing well after the Sept. 22 operation. The organ passed an early test by avoiding hyperacute rejection.

Physicians for the patient, a 58-year-old former lab tech repeatedly turned down for standard allograft transplantation, say they are making good use of lessons from last year’s case of David Bennett, who survived in hospital with difficulty for 2 months after receiving the first such heart at the center in January 2022.

Mr. Bennett’s clinical course had been promising at first but grew turbulent with repeated bouts of infection followed by adjustments to his aggressive immunosuppressant regimen and other complications.

It was also learned weeks after the xenotransplant operation that the heart from the genetically modified donor pig had carried a porcine cytomegalovirus to Mr. Bennett’s body, although there was never evidence that the virus infected other organs or played a major role in his death.

The new xenotransplant recipient, Lawrence Faucette of Frederick, Md., is benefiting from that experience, which was documented in journal reports.

Mr. Faucette had been turned down by UMMC “and several other leading transplant hospitals due to his pre-existing peripheral vascular disease and complications with internal bleeding,” notes a UMMC press release describing his procedure.

The patient “is currently breathing on his own, and his heart is functioning well without any assistance from supportive devices,” says the statement.

Despite a few setbacks, Mr. Faucette is “on the right track,” said Muhammad M. Mohiuddin, MBBS, surgeon and xenotransplantation program director at the University of Maryland, Baltimore, in an interview.

“We’re taking one day at a time. His immune system is still intact, despite the heavy immune suppression,” he told this news organization. His heart didn’t carry a virus and “has not shown any signs of rejection so far.”

The University of Maryland team, Dr. Mohiuddin said, “is very hopeful that we will be able to at least mobilize the patient, and he can be discharged. But it’s a little too early to call.”

Mr. Faucette, as part of his immunosuppressant regimen, is receiving tegoprubart (Eledon Pharmaceuticals), an investigational antibody that blocks CD40 ligand. His predecessor Mr. Bennett, in contrast, had received a blocker of the CD40 receptor (Kiniksa Pharmaceuticals) along with other more familiar immunosuppressants.

The new anti–CD40-ligand blocker, Eledon said, is in phase 1 studies looking at efficacy in patients with conventional kidney transplants.

A version of this article appeared on Medscape.com.

The second patient to be transplanted with a genetically modified pig heart at the University of Maryland Medical Center (UMMC), Baltimore, is said to be stable and doing well after the Sept. 22 operation. The organ passed an early test by avoiding hyperacute rejection.

Physicians for the patient, a 58-year-old former lab tech repeatedly turned down for standard allograft transplantation, say they are making good use of lessons from last year’s case of David Bennett, who survived in hospital with difficulty for 2 months after receiving the first such heart at the center in January 2022.

Mr. Bennett’s clinical course had been promising at first but grew turbulent with repeated bouts of infection followed by adjustments to his aggressive immunosuppressant regimen and other complications.

It was also learned weeks after the xenotransplant operation that the heart from the genetically modified donor pig had carried a porcine cytomegalovirus to Mr. Bennett’s body, although there was never evidence that the virus infected other organs or played a major role in his death.

The new xenotransplant recipient, Lawrence Faucette of Frederick, Md., is benefiting from that experience, which was documented in journal reports.

Mr. Faucette had been turned down by UMMC “and several other leading transplant hospitals due to his pre-existing peripheral vascular disease and complications with internal bleeding,” notes a UMMC press release describing his procedure.

The patient “is currently breathing on his own, and his heart is functioning well without any assistance from supportive devices,” says the statement.

Despite a few setbacks, Mr. Faucette is “on the right track,” said Muhammad M. Mohiuddin, MBBS, surgeon and xenotransplantation program director at the University of Maryland, Baltimore, in an interview.

“We’re taking one day at a time. His immune system is still intact, despite the heavy immune suppression,” he told this news organization. His heart didn’t carry a virus and “has not shown any signs of rejection so far.”

The University of Maryland team, Dr. Mohiuddin said, “is very hopeful that we will be able to at least mobilize the patient, and he can be discharged. But it’s a little too early to call.”

Mr. Faucette, as part of his immunosuppressant regimen, is receiving tegoprubart (Eledon Pharmaceuticals), an investigational antibody that blocks CD40 ligand. His predecessor Mr. Bennett, in contrast, had received a blocker of the CD40 receptor (Kiniksa Pharmaceuticals) along with other more familiar immunosuppressants.

The new anti–CD40-ligand blocker, Eledon said, is in phase 1 studies looking at efficacy in patients with conventional kidney transplants.

A version of this article appeared on Medscape.com.

The second patient to be transplanted with a genetically modified pig heart at the University of Maryland Medical Center (UMMC), Baltimore, is said to be stable and doing well after the Sept. 22 operation. The organ passed an early test by avoiding hyperacute rejection.

Physicians for the patient, a 58-year-old former lab tech repeatedly turned down for standard allograft transplantation, say they are making good use of lessons from last year’s case of David Bennett, who survived in hospital with difficulty for 2 months after receiving the first such heart at the center in January 2022.

Mr. Bennett’s clinical course had been promising at first but grew turbulent with repeated bouts of infection followed by adjustments to his aggressive immunosuppressant regimen and other complications.

It was also learned weeks after the xenotransplant operation that the heart from the genetically modified donor pig had carried a porcine cytomegalovirus to Mr. Bennett’s body, although there was never evidence that the virus infected other organs or played a major role in his death.

The new xenotransplant recipient, Lawrence Faucette of Frederick, Md., is benefiting from that experience, which was documented in journal reports.

Mr. Faucette had been turned down by UMMC “and several other leading transplant hospitals due to his pre-existing peripheral vascular disease and complications with internal bleeding,” notes a UMMC press release describing his procedure.

The patient “is currently breathing on his own, and his heart is functioning well without any assistance from supportive devices,” says the statement.

Despite a few setbacks, Mr. Faucette is “on the right track,” said Muhammad M. Mohiuddin, MBBS, surgeon and xenotransplantation program director at the University of Maryland, Baltimore, in an interview.

“We’re taking one day at a time. His immune system is still intact, despite the heavy immune suppression,” he told this news organization. His heart didn’t carry a virus and “has not shown any signs of rejection so far.”

The University of Maryland team, Dr. Mohiuddin said, “is very hopeful that we will be able to at least mobilize the patient, and he can be discharged. But it’s a little too early to call.”

Mr. Faucette, as part of his immunosuppressant regimen, is receiving tegoprubart (Eledon Pharmaceuticals), an investigational antibody that blocks CD40 ligand. His predecessor Mr. Bennett, in contrast, had received a blocker of the CD40 receptor (Kiniksa Pharmaceuticals) along with other more familiar immunosuppressants.

The new anti–CD40-ligand blocker, Eledon said, is in phase 1 studies looking at efficacy in patients with conventional kidney transplants.

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Women who use cocaine, cannabis, or other substances during pregnancy have increased risks of acute cardiovascular (CV) events while in the hospital for delivery, including more than double the risk of maternal mortality, a new study shows.

METHODOLOGY:

• Using the National Inpatient Sample database to identify hospital deliveries between 2004 and 2018 and diagnostic codes to identify maternal substance use, researchers compared 955,531 pregnancies with accompanying substance use – the most common substances being cannabis and opioids, followed by stimulants – to over 60 million pregnancies in which there was no substance use.
• The primary outcome was any CV event, including acute myocardial infarction, stroke, arrhythmia, endocarditis, any acute cardiomyopathy or heart failure, or cardiac arrest; other outcomes included maternal mortality and major adverse cardiac events (MACE).

TAKEAWAY:

• Deliveries complicated by substance use increased from 1,126 per 100,000 deliveries in 2004 to 1,547 per 100,000 in 2018, peaking at 2,187 per 100,000 in 2014.
• After the researchers controlled for patient demographics and CVD risk factors, results showed that pregnant women who used any substance (cannabis, opioids, methamphetamine, alcohol, tobacco, or cocaine) were more likely to experience a CVD event (adjusted odds ratio [aOR], 1.61; 95% confidence interval [CI], 1.53-1.70; P < .001), MACE (aOR, 1.53; 95% CI, 1.46-1.61; P < .001), or maternal mortality (aOR, 2.65; 95% CI, 2.15-3.25; P < .001) during hospitalization for delivery.
• Those using amphetamine/methamphetamine had ninefold higher odds of cardiomyopathy or heart failure and more than sevenfold higher odds of cardiac arrest.

IN PRACTICE:

“For the wellbeing of pregnant women and their children, substance use needs to be considered an independent risk factor for CV events in pregnancy,” the authors wrote. They called for prenatal assessments by a multidisciplinary cardio-obstetrics team to try to decrease cardiac complications.

In an accompanying editorial by Abha Khandelwal, MD, department of medicine, Stanford (Calif.) University, and others, the authors said the findings “highlight the critical support required during pregnancy and postpartum” for substance users, which should include comprehensive medical care and social services as well as access to addiction medicine and treatment of co-occurring mental health disorders.

SOURCE:

The study was carried out by Kari Evans, MD, division of maternal fetal medicine, department of obstetrics and gynecology, University of Arizona, Phoenix. It was published online in the Journal of the American College of Cardiology: Advances.

LIMITATIONS:

Use of administrative databases may have resulted in underreporting of diagnoses. The researchers could not assess the association of dose, duration, method, or timing of use for any substance with CV events. They also could not examine the effect of vaping on maternal CV events or differentiate hospitalizations for delivery that were complicated by CV events from hospitalizations for CV events that prompted delivery. The data did not reflect the postpartum period, during which a high rate of adverse CV events occurs.

DISCLOSURES:

The authors and editorial writers have no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.