Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

Adults who use opioids are more likely to have “complicated health profiles and high levels of involvement in the criminal justice system” compared with adults who do not, according to a retrospective, cross-sectional analysis published July 6 in JAMA Network Open.

“The large proportion of individuals with opioid use disorders who have physical and mental health conditions and who contact the criminal justice system suggests that public health interventions to combat the opioid epidemic ... should coordinate treatment between the criminal justice and health care systems,” wrote Tyler N.A. Winkelman, MD, and his colleagues.

The investigators evaluated a representative sample of responses from 78,976 U.S. adults aged 18-64 who completed the 2015-2016 National Survey on Drug Use and Health, of which 31.3% reported use of prescription opioids, 4.3% reported misuse of opioids, 0.8% reported abuse of prescription opioids, and 0.4% reported heroin use.

The researchers also studied the health characteristics of each individual based on their level of opioid use, whether individuals used other substances in addition to prescription opioids, and the respondents’ recent and distant involvement in the criminal justice system, reported Dr. Winkelman, who is affiliated with the division of general internal medicine at Hennepin Healthcare in Minneapolis, and his colleagues.

After adjustment for health characteristic prevalence and co-occurring substance use across opioid use levels, compared with individuals who reported no opioid use, Dr. Winkelman and his associates found a higher prevalence of mental illness among individuals across four categories: prescription opioid use, prescription opioid misuse, prescription opioid use disorder, and heroin use. They also found a higher prevalence of self-reported chronic conditions such as diabetes, asthma, and high blood pressure across various levels of opioid use, compared with people who reported no opioid use.

Furthermore, Dr. Winkelman and his associates found that as the intensity of opioid use increased, individuals reported an increased prevalence of mild, moderate, and severe mental illness. Individuals who increased their intensity of opioid use also had a greater likelihood of co-occurring substance use with at least one other substance. For example, individuals who misused opioids or used heroin reported that they used tranquilizers or sedatives in more than 50% of cases. Of individuals who reported heroin use, 88.5% said they used prescription opioids within the past year, reported Dr. Winkelman, also a staff physician at the Adult Detention Center in Hennepin County, Minn., and his associates.

The researchers also found 22.4% of individuals (95% confidence interval, 21.7-23.1) who used prescription opioids, 33.2% of individuals who misused prescription opioids (95% CI, 30.9-35.6), 51.7% of individuals with prescription opioid use disorder (95% CI, 45.4-58.0), and 76.8% of individuals with heroin use (95% CI, 70.6-82.1) had any contact with the criminal justice system, compared with 15.9% (95% CI, 15.4-16.4) of individuals who did not report prescription opioid use.

“The overlap we found between involvement in the criminal justice system and opioid use suggests that access to opioid treatment within the criminal justice system is a critical public health issue,” the researchers wrote. They cited studies showing that strategies such as beginning or continuing methadone hydrochloride or buprenorphine hydrochloride during incarceration are tied to a reduction in postrelease mortality.

Among the limitations cited were the National Survey on Drug Use and Health’s cross-sectional design, which makes it difficult to determine whether opioid use preceded involvement in the criminal justice system, or vice versa.

Nevertheless, they said, the study provides the most comprehensive picture to date of the status across several domains of people who use opioids.

“Given the complex health and criminal justice profiles of individuals who use opioids, policy makers should carefully consider how changes to public health insurance programs and sentencing guidelines may aid or hinder a public health approach to the opioid epidemic,” wrote Dr. Winkelman and his colleagues.

Dr. Winkelman disclosed his affiliation with the Hennepin County detention center. Another author disclosed employment with the Colorado Permanente Medical Group and royalties from uptodate.com.

SOURCE: Winkelman TNA et al. JAMA Network Open. 2018 Jul 6. doi: 10.1001/jamanetworkopen.2018.0558.

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

ORLANDO – A new analysis of more than 1.5 million U.S. subjects with diabetes found that chronic kidney disease (CKD) is much more common in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM) – 44% vs. 32%, respectively. The research also provides more evidence that albumin testing can provide crucial warning signs of future kidney trouble.

“Our data suggest – but don’t really prove – that there’s a lot more eGFR testing than there is albumin testing,” said nephrologist and study coauthor Michael Cressman, DO, of Covance, the drug development business of LabCorp, in an interview at the annual scientific sessions of the American Diabetes Association. “It is very important to measure albumin in the urine in order to identify patients who are at highest risk of progressive renal disease. There you identify people for whom you really want to maximize all the available treatments.”

According to the study, previous research has estimated that 25% of U.S. adults with diabetes have CKD (eGFR less than 60 ml/min per 1.73m² or an albumin to creatinine ratio equal to or greater than 30 mg/g), but the difference in rates between T1DM and T2DM has been unclear.

Researchers analyzed LabCorp laboratory data on blood from for 48,036 adults with T1DM and 1,461,915 with T2DM. The analysis included ACR and CKD-EPI calculator for eGFR measurements from 2014-2017.

The researchers tracked declines in eGFR in patients who had more than three eGFR readings over at least 1 year.

Researchers found that the rate of CKD was 40% higher in patients with T2DM than it was in those with T1DM (44% vs. 32%, respectively; P less than .001), as was the prevalence of subjects considered to be at high or very high risk (18% vs. 12%, respectively; P less than .001).

These findings didn’t surprise Dr. Cressman, who said the higher ages of subjects with T2DM could explain the gap since they were more likely to have been exposed to hypertension for longer amounts of time.

Researchers also reported that the median eGFR decline (ml/min per year) was especially high in those with macroalbuminuria: –3.80 in T1DM and –3.58 in T2DM.

“Although MA [macroalbuminuria] is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1DM and T2DM,” the researchers wrote.

“While it’s been known for a while that it’s bad to have albumin, this is more of a strong reinforcing piece of data,” Dr. Cressman said. “When you read about these things and it’s an epidemiological study or a clinical trial, it kind of loses its flavor. These are actual patients. A doctor could look at this data and say, ‘I ought to be checking this [albumin].’ It’s sort of an obvious rationale for what the guidelines say.”

No study funding was reported. Dr. Cressman reported employment by Covance. Other study authors variously report no disclosures or employment by Covance and its parent company LabCorp and stock/shareholding in LabCorp.

sworcester@mdedge.com

SOURCE: Cressman M et al. ADA 2018, Abstract 544-P.
 

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

cpalmer@mdedge.com

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

cpalmer@mdedge.com

The Food and Drug Administration has released revised guidance regarding testing blood donations for Zika virus, moving away from individual testing of donations and toward pooled testing.

“This [practice of pooled testing] is usually more cost effective and less burdensome for blood establishments,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in the statement. “However, the FDA will continue to monitor the situation closely and, as appropriate, reconsider what measures are needed to maintain the safety of the blood supply.”

cpalmer@mdedge.com

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

The Robotic Versus Laparoscopic Ventral Hernia Repair study is an interventional trial recruiting patients undergoing elective ventral hernia repair appropriate for minimally invasive surgery.

The trial will compare outcomes of laparoscopic and robotic approaches to ventral hernia repair. The robotic approach to ventral hernia repair previously had been associated with improved outcomes and reduced hospital stay times, compared with the laparoscopic approach, and has been endorsed by the American Hernia Society. However, this evidence is based on database and cohort studies, and more randomized, controlled trials are needed to assess the true effects of the robotic approach.

Patients will be included if they are scheduled for a ventral hernia repair that has been deemed appropriate for minimally invasive surgery. Exclusion criteria include being unlikely to survive for 2 years post surgery, being unlikely to follow up, having advanced chronic obstructive pulmonary disease or congestive heart failure, having a history of open abdomen or extensive lysis of adhesions, having ascites caused by cirrhosis or malignancy, having an active infection, and having a hernia defect size larger than 12 cm.

The primary outcome measure is total number of days spent in the hospital. Secondary outcomes include rates of surgical site infection, rates of surgical site occurrence, rates of hernia reoccurrence, patient-centered outcomes collected using HerQLes (a hernia quality of life measuring instrument), patient-centered outcomes collected using the EQ-5D questionnaire, and cost from a health care perspective.

The primary completion date is April 30, 2020, and the study completion date is April 30, 2023. About 120 people are expected to be recruited.

Find more information on the study page at Clinicaltrials.gov.

lfranki@mdedge.com

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

Tranexamic Acid May Benefit Patients With Stroke

Patients with intracerebral hemorrhage may benefit from receiving a drug currently used to treat blood loss from major trauma and bleeding after childbirth, according to an international trial.

The study, led by experts at the University of Nottingham in the United Kingdom and funded by the National Institute for Health Research (NIHR) Health Technology Assessment Program, found that giving tranexamic acid to people who had had intracerebral hemorrhage reduced the number of deaths in the early days following the stroke. It also found that the amount of bleeding in the brain and number of associated serious complications were lower in the patients who had received tranexamic acid treatment.

However, the investigators found no difference in the number of people who were left disabled or had died at three months after their stroke (ie, the study’s primary outcome). The researchers believe that further study is needed on larger groups of patients to enable them to fully understand the potential benefits.

Nikola Sprigg, MD, Professor of Stroke Medicine at the Stroke Trials Unit in the university’s Division of Clinical Neuroscience, led the trial. “Tranexamic acid is cheap, costing less than £15 per patient, and widely available, so it has the potential for reducing death and disability across the world,” she said.

“While we failed to show significant benefits three months after stroke, the reduction in early deaths, amount of bleeding on the brain, and serious complications are signs that this drug may be of benefit in the future. More trials are needed, particularly focusing on giving treatment as soon as possible after the start of bleeding in this emergency condition,” Dr. Sprigg added.

Approximately 15% of all strokes in the UK—affecting around 22,000 people every year—are hemorrhagic and lead to permanent damage. While all people with acute stroke benefit from treatment on a stroke unit, there is currently no specific treatment for hemorrhagic stroke. Many people with hemorrhagic stroke die within a few days. Those who do survive are often left with debilitating disabilities, including paralysis and an inability to speak.

A previous small pilot study by the University of Nottingham and funded by the university and the Stroke Association concluded that a larger study was needed to accurately assess the effectiveness of tranexamic acid. The drug was chosen for the study after previous research showed that it was successful in stopping bleeding in people involved in car accidents.

For the latest trial, people who were diagnosed with bleeding on the brain, confirmed by CT scan, were offered the chance to take part in the study. When the person was too ill to decide, permission was asked of their family or close friends. When no family members were available, a doctor unconnected with the study decided whether the patient should take part.

The five-year TICH-2 trial recruited more than 2,000 patients from 124 hospitals in 12 countries between 2013 and 2017. They were randomly sorted into two patient groups. One received tranexamic acid within eight hours of stroke, and the other was given a saline placebo. In the UK, more than 80 hospitals took part in the study with support from the NIHR clinical research network.

CT scans of the patients’ brains were performed at 24 hours after their stroke, and patients’ progress was monitored and measured at day two and day seven after their stroke. The final follow-up was performed at 90 days.

Tranexamic acid did not improve the outcome for patients after 90 days; there was no significant difference in the number of patients who had subsequently died or had been left with disabilities between the tranexamic acid and placebo groups at three months.

In the tranexamic acid group, however, there were fewer deaths by day seven following the stroke. At day two, fewer people on tranexamic acid experienced a worsening of the bleed on their brain, and they had smaller amounts of blood in the brain, compared with their control group counterparts. Also, the number of patients who had associated serious complications such as pneumonia and brain swelling was lower in the group that had received tranexamic acid treatment, compared with controls.

The trial also found evidence that tranexamic acid might be more effective in patients with lower blood pressure. Participants with blood pressure lower than 170 mm Hg had a more favorable outcome than those with blood pressure of 170 mm Hg and above. Other studies have confirmed that the sooner tranexamic acid is given, the more effective it is. The ideal is to administer the drug within three hours of bleeding onset, according to the researchers. In this study, one-third of patients were given treatment within three hours of stroke onset.

As a result, the researchers have highlighted the need for further studies to find out whether giving an earlier dose of tranexamic acid might be beneficial for patients.

Combination Therapy May Prevent Stroke

Results from an international clinical trial of more than 4,880 participants show that combining clopidogrel and aspirin following a small stroke or experiencing minor stroke symptoms decreases the risk of a new stroke, heart attack, or other ischemic event within 90 days. The combination therapy was also associated with an increase in major bleeding, although many of those episodes were nonfatal and did not occur in the brain. The results were published in the New England Journal of Medicine. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), a part of NIH.

“These findings are likely to have a global effect on clinical practice, as these drugs are easily available in many hospitals and clinics,” said Walter Koroshetz, MD, Director of NINDS. “As the benefit of the combination was concentrated in the first two weeks, while risk of bleeding was constant over 90 days, it may be especially valuable in acute management of a minor ischemic stroke or transient ischemic attack (TIA).”

The Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) clinical trial follows an earlier study that showed benefits of this drug combination in a Chinese population. POINT was conducted to see whether the benefits could be expanded to a more diverse group of patients.

The study, led by S. Claiborne Johnston, MD, PhD, Dean and Professor of Neurology at Dell Medical School at the University of Texas at Austin, included patients who had had either a minor stroke or a TIA, in which blood supply to a part of the brain is briefly stopped and can be a risk factor for a larger stroke. Study participants were given clopidogrel and aspirin or aspirin alone to see whether the combination therapy could prevent a larger stroke within three months.

Dr. Johnston’s team found that the combination of clopidogrel and aspirin prevented more ischemic events, such as stroke and heart attack, compared with aspirin alone. The results showed that 5% of patients in the combination therapy group and 6.5% of patients taking only aspirin had such an event within 90 days. The combination therapy was associated with a greater risk of major bleeding or hemorrhage than aspirin alone, however. In the aspirin-only group, 0.4% of patients suffered a major hemorrhage, but 0.9% of patients taking clopidogrel and aspirin had severe bleeding.

The findings suggest that for 1,000 patients, clopidogrel plus aspirin would prevent 15 ischemic attacks, but may cause five instances of major hemorrhage. The majority of these hemorrhages occurred outside of the brain and were not fatal.

“We saw a real benefit with the combination therapy, but that treatment does come with a risk,” said Dr. Johnston. “Overall, the risk of severe bleeding was very small, but it was not zero.”

The study was stopped early because the combination therapy was found to be more effective than aspirin alone in preventing severe strokes, but also due to the risk of severe hemorrhage.

Clopidogrel and aspirin prevent platelets from sticking together and forming clots in blood vessels, although they work in different ways. Aspirin blocks molecules that activate the clotting process, while clopidogrel prevents a specific chemical from attaching to a receptor.

“Each year, strokes cause millions of disabilities around the world, and preventing many of those would lead to not only tremendous health savings, but also to improved quality of life for many individuals and their families,” said Dr. Johnston.

POINT was supported by NINDS’s Neurological Emergencies Treatment Trials (NETT) Network, a system of research institutions dedicated to emergency issues such as stroke.

More research is needed to investigate ways to lower the risk of bleeding and examine the impact of treatment timing on outcomes. In addition, future studies may help identify similar drugs that are associated with fewer adverse events.

Simple Scan Still Effective in Deciding Stroke Treatment

A study led by a neurologist from McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) showed that a CT scan could be sufficient for determining thrombectomy treatment in stroke.

Thrombectomy has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset. Stroke is the leading cause of long-term disability and the fourth leading cause of death globally. Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy. Physicians use noncontrast simple CT or CT perfusion to see the area.

“The results show that simple imaging, while not perfect, may be good enough. This basic technique is faster, which means patients could potentially be treated more quickly,” said Amrou Sarraj, MD, Associate Professor of Neurology at McGovern Medical School at UTHealth. “The advanced imaging of CT perfusion is not available everywhere, so this could open up the door to identify more people for potential treatment, especially in remote areas.”

Dr. Sarraj was the principal investigator of the study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT). The clinical trial enrolled 445 patients who received both simple and advanced imaging at nine academic health centers across the US from January 2016 to February 2018.

The results showed that patients who were treated based on simple imaging had identical clinical outcomes to those treated based on advanced imaging. In addition, those patients who had a good imaging profile (ie, a smaller area of dead brain tissue) had the same clinical outcomes, regardless of which imaging was used.

“If those treated using simple imaging can do as well as those treated by CT perfusion, this is an extremely important breakthrough that warrants further exploration and testing because it could broaden the number of patients having and benefiting from thrombectomy,” said Dr. Sarraj, who is also director of UTHealth’s vascular neurology fellowship program and an attending physician at Memorial Hermann-Texas Medical Center.

The study also revealed that 42% of patients who were excluded from thrombectomy by one of the imaging profiles, but had a good profile on the other type of imaging, had positive clinical outcomes.

“Our results should not be interpreted [to indicate] that advanced perfusion images are not necessary or should not be acquired at all, as they still identified a group of patients that may be treated with thrombectomy when CT alone was not enough. The numbers involved are significant because 17.6% of patients could have been excluded from having surgery if the CT or CT perfusion were relied on alone, so there is a real opportunity here to help more people if both forms of imaging are available,” Dr. Sarraj said.

The study did not randomize patient selection by simple imaging versus advanced imaging. “Although this was the first large cohort study with prespecified imaging criteria, analyses, and objectives to look at imaging type selection, there is room for further refinement to truly test our initial findings and see if they are more affirmative and conclusive,” Dr. Sarraj said.

Thrombolysis May Be Appropriate in Wake-Up Stroke

The randomized controlled WAKE-UP trial, a phase III study of 503 patients with acute stroke of unknown time of symptom onset, assessed whether or not advanced imaging can be used to increase the number of patients eligible for potent clot-busting drugs to include patients waking with a stroke.

The WAKE-UP study showed that in patients with stroke and unknown time of symptom onset and an MRI pattern demonstrating DWI-FLAIR-mismatch, indicating a likely recent time of onset, treatment with alteplase resulted in a better functional outcome at 90 days in an additional 11% of treated patients, compared with placebo, despite an increased risk of intracerebral hemorrhage. The effect size of MRI-guided thrombolysis in stroke with unknown time of symptom onset is comparable to the effect size of thrombolysis administered at less than 4.5 hours. The researchers observed a trend towards an increased risk of early death, however.

The joint lead investigators of WAKE-UP commented on the results. “These data represent a paradigm shift in the treatment of stroke patients with an unknown time of symptom onset,” said Professor Christian Gerloff, MD, Director of Neurology at University Hospital Hamburg-Eppendorf in Germany. “It is the first positive trial of IV thrombolysis relying on patient selection by advanced brain imaging without information on time of symptom onset.”

“MRI-guided IV thrombolysis represents an effective treatment option for stroke patients with unknown [time of] symptom onset, especially for those with minor or moderate stroke who are not eligible for mechanical thrombectomy,” said Götz Thomalla, MD, Executive Senior Physician at University Hospital Hamburg-Eppendorf.

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

cpalmer@mdedge.com

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.
 

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

cpalmer@mdedge.com

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.
 

The more sexual refusals men received in a virtual dating simulation, the more hostile the verbal comments men made to the women – regardless of the amount of alcohol the men had consumed, according to a study published in Aggressive Behavior.

“Contrary to our predictions [the relationship between sexual refusals and hostile comments] was not moderated by alcohol condition,” reported Jacqueline Woerner, PhD, and her colleagues. “Because participants had multiple opportunities to escalate their aggression or desist, this paradigm provides new insights into the mechanisms through which intoxication enhances the likelihood of sexual aggression in dating situations.”Dr. Woerner and her colleagues used a virtual dating simulation to compare the sexual aggression of 31 intoxicated men with that of an equal number sober controls. The men, aged 21-29 years and largely white, received either a mixed alcoholic drink adjusted to achieve a blood alcohol concentration of 0.08% or an alcohol-free beverage.

The men went on four computer-mediated dates with a virtual woman; the simulated dates covered a span of a couple of months during the session. The woman was programmed to always consent to some lower-level sexual activities (such as kissing), to consent to some medium-level activities (such as touching breasts) only during later dates, but to always refuse higher-level sexual activities (such as vaginal or oral sex).

As hypothesized, the number of consensual sexual activities correlated with the number of refusals, which suggested that, per expectancy confirmation theory, these men tended to focus on earlier cues that confirmed mutual sexual desire and to ignore those that suggested that the woman was no longer interested, according to the researchers. This correlation and the behaviors it suggests were significantly stronger among intoxicated men than they were among sober controls, reported Dr. Woerner, now affiliated with Yale University, New Haven, Conn., and her colleagues.

However, when the researchers examined the impact of alcohol on the relationship between sexual refusals and the number of hostile verbal comments, they got surprising results. The connection between sexual refusals and alcohol condition was not significant. Among the possible explanations for this unexpected finding were the “extremely high levels of hostility” of some men toward women and the sense of entitlement of some men toward women – whether the men are intoxicated or sober. “Perpetrators’ motives and situational triggers differ, thus multiple explanations need to be evaluated in further research,” Dr. Woerner and her colleagues wrote.

Dr. Woerner and her colleagues also recorded audio of participants as they interacted with the simulation. The intensity of the commentary – with comments like “You prude, we’ve been hanging out for months now” – suggested the participants took the simulation seriously, the researchers noted.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

cpalmer@mdedge.com

SOURCE: Woerner J et al. Aggress Behav. 2018. doi: 10.1002/ab.21773.
 

ORLANDO – The cardioprotective benefits of canagliflozin as demonstrated in patients with type 2 diabetes mellitus are similar across varying levels of kidney function, according to an analysis of data from the CANVAS program.

The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.

Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m² [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m² [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m² [554 patients], 45-60 mL/min per 1.72 m² [1,485 patients], 60-90 mL/min per1.72 m² [5,625 patients], and 90 or greater mL/min per 1.72 m² [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.

An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.

As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA_1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.

“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.

For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.

“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.

For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).

For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.

As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.

“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.

The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.

“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA_1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.

“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.

The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.

sworcester@mdedge.com

SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.

ORLANDO – The cardioprotective benefits of canagliflozin as demonstrated in patients with type 2 diabetes mellitus are similar across varying levels of kidney function, according to an analysis of data from the CANVAS program.

The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.

Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m² [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m² [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m² [554 patients], 45-60 mL/min per 1.72 m² [1,485 patients], 60-90 mL/min per1.72 m² [5,625 patients], and 90 or greater mL/min per 1.72 m² [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.

An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.

As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA_1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.

“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.

For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.

“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.

For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).

For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.

As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.

“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.

The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.

“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA_1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.

“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.

The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.

sworcester@mdedge.com

SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.

ORLANDO – The cardioprotective benefits of canagliflozin as demonstrated in patients with type 2 diabetes mellitus are similar across varying levels of kidney function, according to an analysis of data from the CANVAS program.

The findings suggest that it may be time to reconsider limitations on usage of the sodium-glucose transporter 2 inhibitor in patients with poor kidney function, Dick de Zeeuw, MD, PhD, said at the annual scientific sessions of the American Diabetes Association.

Despite the smaller glycemic effects in patients with reduced estimated glomerular filtration rate (eGFR) seen in CANVAS (CANagliflozin cardioVascular Assessment Study), the relative effects on the primary – and most other – cardiovascular outcomes in CANVAS were similar in patients with low (less than 60 mL/min per 1.72 m² [2,029 patients]) versus high (greater than 60 mL/min per 1.72 m² [8,101 patients]) eGFR, and across four eGFR subgroups (less than 45 mL/min per 1.72 m² [554 patients], 45-60 mL/min per 1.72 m² [1,485 patients], 60-90 mL/min per1.72 m² [5,625 patients], and 90 or greater mL/min per 1.72 m² [2,684 patients]), reported Dr. de Zeeuw of the University Medical Center Groningen, the Netherlands.

An exception was a possible finding of heterogeneity of treatment effect for the exploratory outcome of stroke, he noted.

As expected, the effects of canagliflozin versus placebo on the surrogate marker of HbA_1c was significantly smaller with lower renal function, with reductions of 0.35%, 0.45%, 0.57%, and 0.76% across the four eGFR subgroups, respectively.

“But most interestingly, the three other cardiovascular risk markers show no difference in the effect of canagliflozin when we compare them for the four different eGFR groups,” he said, explaining that reductions in systolic blood pressure, body weight, and albuminuria were “very consistent” across the groups.

For the CANVAS 3-point major cardiac adverse event primary endpoint, which included a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (and which was reduced by 14% [hazard ratio, 0.86] with canagliflozin treatment in the primary CANVAS analysis), no significant heterogeneity for treatment effect was noted between the high versus low eGFR groups or the four eGFR groups (P = .08 and .33, respectively), Dr. de Zeeuw said.

“If anything, there was more effect in the low eGFR group than in the high eGFR group [HRs, 0.92 and 0.70, respectively; 0.65, 0.71, 0.95, and 0.84 for the four eGFR groups, respectively]”, he added, noting that the same was true for the cardiovascular death and MI components of the primary endpoint.

For stroke, however, possible heterogeneity by baseline kidney function was noted. In the primary CANVAS analysis, canagliflozin was associated with a nonsignificant 13% reduction in stroke risk (HR, 0.87), and the hazard ratios for low versus high eGFR in the current analysis were 0.50 and 1.01, respectively, and in the four eGFR groups they were 0.32, 0.56, 0.89, and 1.42 , respectively (P = .01 for both comparisons).

For the secondary endpoints of hospitalizations for heart failure and renal function (a composite of eGFR, end-stage kidney disease, or renal death), which both were important outcomes in the CANVAS program with each showing highly significant reductions with canagliflozin treatment versus placebo in the primary analysis (HRs, 0.67 and 0.60), no heterogeneity by eGFR was seen in the current analysis.

As for safety outcomes, which included serious adverse events, adverse events leading to treatment discontinuation, amputation, fractures, and renal safety (serious renal-related adverse events, serious acute kidney injury, and serious hyperkalemia), no heterogeneity was seen in the outcomes across eGFR groups, he said.

“The CANVAS program ... is a composite of two cardiovascular safety trials that have been conducted over the past [8+] years,” Dr. de Zeeuw said, noting that participants included patients with type 2 diabetes mellitus and cardiovascular disease or high cardiovascular risk who were treated with either 300 mg or 100 mg of canagliflozin or with placebo after a 2-week placebo run-in.

The outcomes favored canagliflozin across all endpoints, and particularly for the secondary endpoints of hospitalization for heart failure and the composite of renal outcomes.

“The interest [in terms of the current analysis] is that this drug supposedly works better in those that have a functioning kidney and a filtering kidney, where the tubule is actually the target of this drug. It was anticipated that there would be less effect of this drug on low renal functions,” he said, adding that although the effect on HbA_1c is progressively attenuated with declining renal function, as expected, the effects on other cardiovascular risk markers were, surprisingly, very comparable across the eGFR subgroups.

“And with that, more importantly, the effect on the hard outcomes – like the primary outcomes, most of the CV outcomes [maybe except stroke], the renal and safety outcomes – are very consistent across the different kidney function levels,” he said, adding that these beneficial findings in patients with 30-45 eGFR who are at high cardiovascular and renal risk suggest that reconsideration of the current limitation on the use of canagliflozin inhibitors to patients with eGFR above 45 is warranted.

The CANVAS program was sponsored by Janssen Research & Development. Dr. de Zeeuw is a consultant and/or speaker for AbbVie, Astellas, Bayer, Boehringer Ingelheim, Fresenius, Janssen, and Mitsubishi Tanabe.

sworcester@mdedge.com

SOURCE: de Zeeuw D et al. ADA 2018, Abstract 258-OR.

BALTIMORE—A single night of light exposure during sleep may acutely affect insulin resistance, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. Studies have found that nighttime artificial light exposure affects circadian rhythms such as melatonin and sleep, and disturbances in these rhythms may affect cardiometabolic function.

To assess whether light exposure during sleep negatively affects cardiometabolic outcomes, possibly via disruptions to sleep architecture and melatonin profile, Ivy C. Mason, PhD, a research fellow at Harvard Medical School in Boston, and colleagues conducted a study in which they randomized 20 healthy adults ages 18 to 40 to different sleep conditions. The conditions were run in parallel for three days and two nights.

One group slept in the dark (ie, less than 3 lux) on the first night and in a lighted room (ie, with an overhead light of 100 lux) on the second night. The other group slept in the dark on both nights.

Participants had eight hours of sleep opportunity each night, starting at a habitual bedtime that was determined from one week of actigraphy with a sleep diary. On both nights, overnight polysomnography was performed and hourly blood samples were collected to measure melatonin.

Researchers performed oral glucose tolerance tests on both mornings and assessed changes from the first morning to the second morning. They compared the groups using repeated measures analysis of variance.

The dark–light group (n = 10; two males) had a mean age of 26.61 and a mean BMI of 23.25 kg/m2. The dark–dark group (n = 10; four males) had a mean age of 26.78 and a mean BMI of 24.25 kg/m2).

Homeostatic model assessments of insulin resistance values were significantly higher in the morning following sleep in the light in the dark–light group, compared with those values in the dark–dark group. This effect was primarily due to increased insulin levels in the group that slept in the light, said the researchers.

“Our preliminary findings show that a single night of light exposure during sleep acutely impacts measures of insulin resistance,” said Dr. Mason. “These results are important, given the increasingly widespread use of artificial light exposure, particularly at night.… More research is needed to determine if chronic overnight light exposure during sleep has long-term, cumulative effects on metabolic function.”

BALTIMORE—A single night of light exposure during sleep may acutely affect insulin resistance, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. Studies have found that nighttime artificial light exposure affects circadian rhythms such as melatonin and sleep, and disturbances in these rhythms may affect cardiometabolic function.

To assess whether light exposure during sleep negatively affects cardiometabolic outcomes, possibly via disruptions to sleep architecture and melatonin profile, Ivy C. Mason, PhD, a research fellow at Harvard Medical School in Boston, and colleagues conducted a study in which they randomized 20 healthy adults ages 18 to 40 to different sleep conditions. The conditions were run in parallel for three days and two nights.

One group slept in the dark (ie, less than 3 lux) on the first night and in a lighted room (ie, with an overhead light of 100 lux) on the second night. The other group slept in the dark on both nights.

Participants had eight hours of sleep opportunity each night, starting at a habitual bedtime that was determined from one week of actigraphy with a sleep diary. On both nights, overnight polysomnography was performed and hourly blood samples were collected to measure melatonin.

Researchers performed oral glucose tolerance tests on both mornings and assessed changes from the first morning to the second morning. They compared the groups using repeated measures analysis of variance.

The dark–light group (n = 10; two males) had a mean age of 26.61 and a mean BMI of 23.25 kg/m2. The dark–dark group (n = 10; four males) had a mean age of 26.78 and a mean BMI of 24.25 kg/m2).

Homeostatic model assessments of insulin resistance values were significantly higher in the morning following sleep in the light in the dark–light group, compared with those values in the dark–dark group. This effect was primarily due to increased insulin levels in the group that slept in the light, said the researchers.

“Our preliminary findings show that a single night of light exposure during sleep acutely impacts measures of insulin resistance,” said Dr. Mason. “These results are important, given the increasingly widespread use of artificial light exposure, particularly at night.… More research is needed to determine if chronic overnight light exposure during sleep has long-term, cumulative effects on metabolic function.”

BALTIMORE—A single night of light exposure during sleep may acutely affect insulin resistance, according to research described at the 32nd Annual Meeting of the Associated Professional Sleep Societies. Studies have found that nighttime artificial light exposure affects circadian rhythms such as melatonin and sleep, and disturbances in these rhythms may affect cardiometabolic function.

To assess whether light exposure during sleep negatively affects cardiometabolic outcomes, possibly via disruptions to sleep architecture and melatonin profile, Ivy C. Mason, PhD, a research fellow at Harvard Medical School in Boston, and colleagues conducted a study in which they randomized 20 healthy adults ages 18 to 40 to different sleep conditions. The conditions were run in parallel for three days and two nights.

One group slept in the dark (ie, less than 3 lux) on the first night and in a lighted room (ie, with an overhead light of 100 lux) on the second night. The other group slept in the dark on both nights.

Participants had eight hours of sleep opportunity each night, starting at a habitual bedtime that was determined from one week of actigraphy with a sleep diary. On both nights, overnight polysomnography was performed and hourly blood samples were collected to measure melatonin.

Researchers performed oral glucose tolerance tests on both mornings and assessed changes from the first morning to the second morning. They compared the groups using repeated measures analysis of variance.

The dark–light group (n = 10; two males) had a mean age of 26.61 and a mean BMI of 23.25 kg/m2. The dark–dark group (n = 10; four males) had a mean age of 26.78 and a mean BMI of 24.25 kg/m2).

Homeostatic model assessments of insulin resistance values were significantly higher in the morning following sleep in the light in the dark–light group, compared with those values in the dark–dark group. This effect was primarily due to increased insulin levels in the group that slept in the light, said the researchers.

“Our preliminary findings show that a single night of light exposure during sleep acutely impacts measures of insulin resistance,” said Dr. Mason. “These results are important, given the increasingly widespread use of artificial light exposure, particularly at night.… More research is needed to determine if chronic overnight light exposure during sleep has long-term, cumulative effects on metabolic function.”

For men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), a docetaxel-containing nanoparticle directed against prostate-specific membrane antigen (PSMA) was both active and well tolerated.

Among 42 men with mCRPC that had progressed after treatment with abiraterone acetate (Zytiga) and/or enzalutamide (Xtandi), the 6-month radiographic progression-free survival (PFS) rate, the primary endpoint, was 65%, and approximately one-third of evaluable patients had a prostate-specific antigen (PSA) response and measurable disease response, reported Karen A. Autio, MD, MSc, of Memorial Sloan Kettering Cancer Center, New York, and her colleagues.

Treatment with the PSMA-directed docetaxel-containing nanoparticle, called BIND-014, was also associated in some patients with a rapid and robust decline in PSMA-positive circulating tumor cells (CTCs), the investigators noted. The report was published in JAMA Oncology.

“Many aspects of our study – reductions in PSA, radiographically confirmed disease control in bone and visceral metastatic disease, favorable CTC conversions, and an acceptable adverse effect profile – were promising for BIND-014. However, standard therapy with docetaxel is widely used and effective in treating this disease, and as a natural comparator for a phase 3 randomized clinical trial with BIND-014, it sets a high bar for efficacy in an unselected population,” they wrote.

Their findings suggest that patients with PSMA-positive CTCs might be good candidates for treatment with BIND-014, which is associated with lower toxicities than standard docetaxel, the investigators said.

In the open-label phase 2 trial, 42 men (median age 66) with chemotherapy-naive mCRPC that had progressed on abiraterone and/or enzalutamide were treated with intravenous BIND-014 at dosages of 60 mg/m² on the first day of each 21-day cycle, plus prednisone 5 mg twice daily, until disease progression, intolerable toxicity, or treatment discontinuation at the treating physician’s discretion.

The median number of doses delivered was six.

Of 40 evaluable patients, 12 (30%) had a PSA response, defined as a decrease of 50% or greater from baseline. Among 19 patients with disease measurable according to Response Evaluation Criteria in Solid Tumors, version 1.1, six (32%) had responses, including one complete response and five partial responses. Nine other patients had stable disease.

The median PFS was 9.9 months. As noted, the radiographic PFS rate at 6 months was 65% (26 of 40 patients).

CTC enumeration was performed on samples from 39 patients, of whom 67% had unfavorable counts at baseline, defined as 5 or more CTCs per 7.5 mL of blood.

After treatment, 13 of the patients had a conversion to a favorable count, including 6 whose CTCs became undetectable.

The most common treatment-related adverse events were fatigue, occurring in 69% of patients, nausea in 55%, diarrhea in 45%, and patient-reported neuropathy in 33%. Most toxicities were grade 1 or 2.

Grade 3 or 4 hematological toxicities included lymphopenia in five patients, anemia in three, neutropenia in one, leukopenia in one, and febrile neutropenia in one.

Nonhematological grade 3 or 4 events included fatigue and nausea in two patients each, and dyspnea and decreased appetite in one patient each.

“In this trial, two principal lessons are worth highlighting: the reduction in both total CTCs, which is a marker of clinical benefit, and specifically PSMA-positive CTCs, suggests that the detection of PSMA-positive CTCs before treatment can be used to identify patients who are most likely to benefit in addition to serving as a pharmacodynamic measure,” the investigators wrote.

“Second, there was marked intrapatient and interpatient heterogeneity of PSMA expression on CTCs. This underscores the complexity of targeting tumors with single cell-surface markers,” they wrote.
 

SOURCE: Autio KA et al. JAMA Oncol. 2018 July 5 doi: 10.1001/jamaoncol.2018.2168.

For men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), a docetaxel-containing nanoparticle directed against prostate-specific membrane antigen (PSMA) was both active and well tolerated.

Among 42 men with mCRPC that had progressed after treatment with abiraterone acetate (Zytiga) and/or enzalutamide (Xtandi), the 6-month radiographic progression-free survival (PFS) rate, the primary endpoint, was 65%, and approximately one-third of evaluable patients had a prostate-specific antigen (PSA) response and measurable disease response, reported Karen A. Autio, MD, MSc, of Memorial Sloan Kettering Cancer Center, New York, and her colleagues.

Treatment with the PSMA-directed docetaxel-containing nanoparticle, called BIND-014, was also associated in some patients with a rapid and robust decline in PSMA-positive circulating tumor cells (CTCs), the investigators noted. The report was published in JAMA Oncology.

“Many aspects of our study – reductions in PSA, radiographically confirmed disease control in bone and visceral metastatic disease, favorable CTC conversions, and an acceptable adverse effect profile – were promising for BIND-014. However, standard therapy with docetaxel is widely used and effective in treating this disease, and as a natural comparator for a phase 3 randomized clinical trial with BIND-014, it sets a high bar for efficacy in an unselected population,” they wrote.

Their findings suggest that patients with PSMA-positive CTCs might be good candidates for treatment with BIND-014, which is associated with lower toxicities than standard docetaxel, the investigators said.

In the open-label phase 2 trial, 42 men (median age 66) with chemotherapy-naive mCRPC that had progressed on abiraterone and/or enzalutamide were treated with intravenous BIND-014 at dosages of 60 mg/m² on the first day of each 21-day cycle, plus prednisone 5 mg twice daily, until disease progression, intolerable toxicity, or treatment discontinuation at the treating physician’s discretion.

The median number of doses delivered was six.

Of 40 evaluable patients, 12 (30%) had a PSA response, defined as a decrease of 50% or greater from baseline. Among 19 patients with disease measurable according to Response Evaluation Criteria in Solid Tumors, version 1.1, six (32%) had responses, including one complete response and five partial responses. Nine other patients had stable disease.

The median PFS was 9.9 months. As noted, the radiographic PFS rate at 6 months was 65% (26 of 40 patients).

CTC enumeration was performed on samples from 39 patients, of whom 67% had unfavorable counts at baseline, defined as 5 or more CTCs per 7.5 mL of blood.

After treatment, 13 of the patients had a conversion to a favorable count, including 6 whose CTCs became undetectable.

The most common treatment-related adverse events were fatigue, occurring in 69% of patients, nausea in 55%, diarrhea in 45%, and patient-reported neuropathy in 33%. Most toxicities were grade 1 or 2.

Grade 3 or 4 hematological toxicities included lymphopenia in five patients, anemia in three, neutropenia in one, leukopenia in one, and febrile neutropenia in one.

Nonhematological grade 3 or 4 events included fatigue and nausea in two patients each, and dyspnea and decreased appetite in one patient each.

“In this trial, two principal lessons are worth highlighting: the reduction in both total CTCs, which is a marker of clinical benefit, and specifically PSMA-positive CTCs, suggests that the detection of PSMA-positive CTCs before treatment can be used to identify patients who are most likely to benefit in addition to serving as a pharmacodynamic measure,” the investigators wrote.

“Second, there was marked intrapatient and interpatient heterogeneity of PSMA expression on CTCs. This underscores the complexity of targeting tumors with single cell-surface markers,” they wrote.
 

SOURCE: Autio KA et al. JAMA Oncol. 2018 July 5 doi: 10.1001/jamaoncol.2018.2168.

For men with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), a docetaxel-containing nanoparticle directed against prostate-specific membrane antigen (PSMA) was both active and well tolerated.

Among 42 men with mCRPC that had progressed after treatment with abiraterone acetate (Zytiga) and/or enzalutamide (Xtandi), the 6-month radiographic progression-free survival (PFS) rate, the primary endpoint, was 65%, and approximately one-third of evaluable patients had a prostate-specific antigen (PSA) response and measurable disease response, reported Karen A. Autio, MD, MSc, of Memorial Sloan Kettering Cancer Center, New York, and her colleagues.

Treatment with the PSMA-directed docetaxel-containing nanoparticle, called BIND-014, was also associated in some patients with a rapid and robust decline in PSMA-positive circulating tumor cells (CTCs), the investigators noted. The report was published in JAMA Oncology.

“Many aspects of our study – reductions in PSA, radiographically confirmed disease control in bone and visceral metastatic disease, favorable CTC conversions, and an acceptable adverse effect profile – were promising for BIND-014. However, standard therapy with docetaxel is widely used and effective in treating this disease, and as a natural comparator for a phase 3 randomized clinical trial with BIND-014, it sets a high bar for efficacy in an unselected population,” they wrote.

Their findings suggest that patients with PSMA-positive CTCs might be good candidates for treatment with BIND-014, which is associated with lower toxicities than standard docetaxel, the investigators said.

In the open-label phase 2 trial, 42 men (median age 66) with chemotherapy-naive mCRPC that had progressed on abiraterone and/or enzalutamide were treated with intravenous BIND-014 at dosages of 60 mg/m² on the first day of each 21-day cycle, plus prednisone 5 mg twice daily, until disease progression, intolerable toxicity, or treatment discontinuation at the treating physician’s discretion.

The median number of doses delivered was six.

Of 40 evaluable patients, 12 (30%) had a PSA response, defined as a decrease of 50% or greater from baseline. Among 19 patients with disease measurable according to Response Evaluation Criteria in Solid Tumors, version 1.1, six (32%) had responses, including one complete response and five partial responses. Nine other patients had stable disease.

The median PFS was 9.9 months. As noted, the radiographic PFS rate at 6 months was 65% (26 of 40 patients).

CTC enumeration was performed on samples from 39 patients, of whom 67% had unfavorable counts at baseline, defined as 5 or more CTCs per 7.5 mL of blood.

After treatment, 13 of the patients had a conversion to a favorable count, including 6 whose CTCs became undetectable.

The most common treatment-related adverse events were fatigue, occurring in 69% of patients, nausea in 55%, diarrhea in 45%, and patient-reported neuropathy in 33%. Most toxicities were grade 1 or 2.

Grade 3 or 4 hematological toxicities included lymphopenia in five patients, anemia in three, neutropenia in one, leukopenia in one, and febrile neutropenia in one.

Nonhematological grade 3 or 4 events included fatigue and nausea in two patients each, and dyspnea and decreased appetite in one patient each.

“In this trial, two principal lessons are worth highlighting: the reduction in both total CTCs, which is a marker of clinical benefit, and specifically PSMA-positive CTCs, suggests that the detection of PSMA-positive CTCs before treatment can be used to identify patients who are most likely to benefit in addition to serving as a pharmacodynamic measure,” the investigators wrote.

“Second, there was marked intrapatient and interpatient heterogeneity of PSMA expression on CTCs. This underscores the complexity of targeting tumors with single cell-surface markers,” they wrote.
 

SOURCE: Autio KA et al. JAMA Oncol. 2018 July 5 doi: 10.1001/jamaoncol.2018.2168.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.

AMSTERDAM – When combined with a tumor necrosis factor inhibitor, NSAIDs provide protection against long-term radiographic progression in patients with ankylosing spondylitis, according to an analysis of more than 500 patients presented at the European Congress of Rheumatology.

At 2 years, relative radiographic protection for TNFi plus NSAIDs was not significantly greater than with TNFi alone, but at 4 years the median mSASSS score was 1.24 points lower (P less than .001) in those receiving low-dose NSAIDs, and 3.31 points lower (P less than .001) in those receiving high-dose NSAIDs.

In the subgroup of patients taking high-dose NSAIDs, the protection from progression was greatest among those receiving the selective COX2-inhibitor celecoxib. In these, the median 3.98 points lower mSASSS score (P less than .001) was already significant at 2 years. At 4 years, the median mSASSS score in those receiving TNFi plus celecoxib was 4.69 points lower (P less than .001).

Further evaluation suggested that the benefit from celecoxib plus TNFi was not just additive but synergistic, according to Dr. Gensler. She reported that neither TNFi nor celecoxib alone provided radiographic protection at 2 or 4 years.

Despite the modeling strategy employed to reduce the effect of bias, Dr. Gensler acknowledged that residual confounding is still possible. But she contended that “a large effect [from a such a variable] would be required to negate the findings.”

One of the messages from this study is that “not all NSAIDs are alike,” Dr. Gensler said. “Despite this, when I sit with a patient across from me, I will still treat the patient based on symptoms and disease activity first, though perhaps choose to be more NSAID selective if this is warranted and feasible.”

SOURCE: Gensler L et al. Ann Rheum Dis. 2018;77(Suppl 2):148. Abstract OP0198.