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Revised dispatch system boosts bystander CPR in those with limited English
The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.
The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).
The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).
But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).
“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.
While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.
“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.
“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.
The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.
Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.
There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.
The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”
That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.
“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”
Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.
“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”
None of the authors or editorialists reported any conflicts of interest.
The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.
The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).
The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).
But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).
“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.
While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.
“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.
“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.
The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.
Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.
There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.
The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”
That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.
“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”
Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.
“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”
None of the authors or editorialists reported any conflicts of interest.
The improved Los Angeles medical dispatch system prompted more callers with limited English proficiency to initiate telecommunicator-assisted cardiopulmonary resuscitation (T-CPR), compared with the previous system, a new study shows.
The Los Angeles Tiered Dispatch System (LA-TDS), adopted in late 2014, used simplified questions aimed at identifying cardiac arrest, compared with the city’s earlier Medical Priority Dispatch System (MPDS).
The result was substantially decreased call processing times, decreased “undertriage” of out-of-hospital cardiac arrest (OHCA), and improved overall T-CPR rates (Resuscitation. 2020 Oct;155:74-81).
But now, a secondary analysis of the data shows there was a much higher jump in T-CPR rates among a small subset of callers with limited English proficiency, compared with those proficient in English (JAMA Network Open. 2021;4[6]:e216827).
“This was an unanticipated, significant, and disproportionate change, but fortunately a very good change,” lead author Stephen Sanko, MD, said in an interview.
While the T-CPR rate among English-proficient callers increased from 55% with the MPDS to 67% with the LA-TDS (odds ratio, 1.66; P = .007), it rose from 28% to 69% (OR, 5.66; P = .003) among callers with limited English proficiency. In the adjusted analysis, the new LA-TDS was associated with a 69% higher prevalence of T-CPR among English-proficient callers, compared with a 350% greater prevalence among callers with limited English proficiency.
“The emergency communication process between a caller and 911 telecommunicator is more complex than we thought, and likely constitutes a unique subsubspecialty that interacts with fields as diverse as medicine, health equity, linguistics, sociology, consumer behavior and others,” said Dr. Sanko, who is from the division of emergency medical services at the University of Southern California in Los Angeles.
“Yet in spite of this complexity, we’re starting to be able to reproducibly classify elements of the emergency conversation that we believe are tied to outcomes we all care about. ... Modulators of health disparities are present as early as the dispatch conversation, and, importantly, they can be intervened upon to promote improved outcomes,” he continued.
The retrospective cohort study was a predefined secondary analysis of a previously published study comparing telecommunicator management of out-of-hospital cardiac arrest over 3 months with the MPDS versus 3 months with the LA-TDS. The primary outcome was the number of patients who received telecommunicator-assisted chest compressions from callers with limited English proficiency.
Of the 597 emergency calls that met the inclusion criteria, 289 (48%) were in the MPDS cohort and 308 (52%) were in the LA-TDS cohort. In the MPDS cohort, 263 callers had English proficiency and 26 had limited proficiency; in the latter cohort, those figures were 273 and 35, respectively.
There were no significant differences between cohorts in the use of real-time translation services, which were employed 27%-31% of the time.
The reason for the overall T-CPR improvement is likely that the LA-TDS was tailored to the community needs, said Dr. Sanko. “Most people, including doctors, think of 911 dispatch as something simple and straightforward, like ordering a pizza or calling a ride share. [But] LA-TDS is a ‘home grown’ dispatch system whose structure, questions, and emergency instructions were all developed by EMS medical directors and telecommunicators with extensive experience in our community.”
That being said, the researchers acknowledge that the reason behind the bigger T-CPR boost in LEP callers remains unclear. Although the link between language and system was statistically significant, they noted “it was not an a priori hypothesis and appeared to be largely attributable to the low T-CPR rates for callers with limited English proficiency using MPDS.” Additionally, such callers were “remarkably under-represented” in the sample, “which included approximately 600 calls over two quarters in a large city,” said Dr Sanko.
“We hypothesize that a more direct structure, earlier commitment to treating patients with abnormal life status indicators as being suspected cardiac arrest cases, and earlier reassurance may have improved caller confidence that telecommunicators knew what they were doing. This in turn may have translated into an increased likelihood of bystander caller willingness to perform immediate life-saving maneuvers.”
Despite a number of limitations, “the study is important and highlights instructive topics for discussion that suggest potential next-step opportunities,” noted Richard Chocron, MD, PhD, Miranda Lewis, MD, and Thomas Rea, MD, MPH, in an invited commentary that accompanied the publication. Dr. Chocron is from the Paris University, Paris Research Cardiovascular Center, INSERM; Dr. Lewis is from the Georges Pompidou European Hospital in Paris; and Dr. Rea is from the Division of Emergency Medical Services, Public Health–Seattle & King County. Both Dr. Lewis and Dr. Rea are also at the University of Washington, Seattle.
“Sanko et al. found that approximately 10% of all emergency calls were classified as limited English proficiency calls in a community in which 19% of the population was considered to have limited English proficiency,” they added. “This finding suggests the possibility that populations with limited English proficiency are less likely to activate 911 for incidence of cardiac arrest. If true, this finding would compound the health disparity observed among those with limited English proficiency. This topic is important in that it transcends the role of EMS personnel and engages a broad spectrum of societal stakeholders. We must listen, learn, and ultimately deliver public safety resources to groups who have not been well served by conventional approaches.”
None of the authors or editorialists reported any conflicts of interest.
FROM JAMA NETWORK OPEN
Prediabetes linked to higher CVD and CKD rates
in a study of nearly 337,000 people included in the UK Biobank database.
The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.
“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
‘Prediabetes is not a benign entity’
“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”
Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.
The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.
The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.
The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).
In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.
Need for comprehensive cardiometabolic risk management
The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.
“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.
An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.
Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.
in a study of nearly 337,000 people included in the UK Biobank database.
The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.
“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
‘Prediabetes is not a benign entity’
“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”
Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.
The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.
The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.
The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).
In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.
Need for comprehensive cardiometabolic risk management
The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.
“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.
An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.
Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.
in a study of nearly 337,000 people included in the UK Biobank database.
The findings suggest that people with prediabetes have “heightened risk even without progression to type 2 diabetes,” Michael C. Honigberg, MD, said at the annual scientific sessions of the American College of Cardiology.
“Hemoglobin A1c may be better considered as a continuous measure of risk rather than dichotomized” as either less than 6.5%, or 6.5% or higher, the usual threshold defining people with type 2 diabetes, said Dr. Honigberg, a cardiologist at Massachusetts General Hospital in Boston.
‘Prediabetes is not a benign entity’
“Our findings reinforce the notion that A1c represents a continuum of risk, with elevated risks observed, especially for atherosclerotic cardiovascular disease [ASCVD], at levels where some clinicians wouldn’t think twice about them. Prediabetes is not a benign entity in the middle-aged population we studied,” Dr. Honigberg said in an interview. “Risks are higher in individuals with type 2 diabetes,” he stressed, “however, prediabetes is so much more common that it appears to confer similar cardio, renal, and metabolic risks at a population level.”
Results from prior observational studies also showed elevated incidence rate of cardiovascular disease events in people with prediabetes, including a 2010 report based on data from about 11,000 U.S. residents, and in a more recent meta-analysis of 129 studies involving more than 10 million people. The new report by Dr. Honigberg “is the first to comprehensively evaluate diverse cardio-renal-metabolic outcomes across a range of A1c levels using a very large, contemporary database,” he noted. In addition, most prior reports did not include chronic kidney disease as an examined outcome.
The primary endpoint examined in the new analysis was the combined incidence during a median follow-up of just over 11 years of ASCVD events (coronary artery disease, ischemic stroke, or peripheral artery disease), CKD, or heart failure among 336,709 adults in the UK Biobank who at baseline had none of these conditions nor type 1 diabetes.
The vast majority, 82%, were normoglycemic at baseline, based on having an A1c of less than 5.7%; 14% had prediabetes, with an A1c of 5.7%-6.4%; and 4% had type 2 diabetes based on an A1c of at least 6.5% or on insulin treatment. Patients averaged about 57 years of age, slightly more than half were women, and average body mass index was in the overweight category except for those with type 2 diabetes.
The primary endpoint, the combined incidence of ASCVD, CKD, and heart failure, was 24% among those with type 2 diabetes, 14% in those with prediabetes, and 8% in those who were normoglycemic at entry. Concurrently with the report, the results appeared online. Most of these events involved ASCVD, which occurred in 11% of those in the prediabetes subgroup (roughly four-fifths of the events in this subgroup), and in 17% of those with type 2 diabetes (nearly three-quarters of the events in this subgroup).
In an analysis that adjusted for more than a dozen demographic and clinical factors, the presence of prediabetes linked with significant increases in the incidence rate of all three outcomes compared with people who were normoglycemic at baseline. The analysis also identified an A1c level of 5.0% as linked with the lowest incidence of each of the three adverse outcomes. And a very granular analysis suggested that a significantly elevated risk for ASCVD first appeared when A1c levels were in the range of 5.4%-5.7%; a significantly increased incidence of CKD became apparent once A1c was in the range of 6.2%-6.5%; and a significantly increased incidence of heart failure began to manifest once A1c levels reached at least 7.0%.
Need for comprehensive cardiometabolic risk management
The findings “highlight the importance of identifying and comprehensively managing cardiometabolic risk in people with prediabetes, including dietary modification, exercise, weight loss and obesity management, smoking cessation, and attention to hypertension and hypercholesterolemia,” Dr. Honigberg said. While these data cannot address the appropriateness of using novel drug interventions in people with prediabetes, they suggest that people with prediabetes should be the focus of future prevention trials testing agents such as sodium-glucose cotransporter 2 inhibitors.
“These data help us discuss risk with patients [with prediabetes], and reemphasize the importance of guideline-directed preventive care,” said Vijay Nambi, MD, PhD, a preventive cardiologist and lipid specialist at Baylor College of Medicine and the Michael E. DeBakey VA Medical Center in Houston, who was not involved with the study.
An additional analysis reported by Dr. Honigberg examined the risk among people with prediabetes who also were current or former smokers and in the top tertile of the prediabetes study population for systolic blood pressure, high non-HDL cholesterol, and C-reactive protein (a marker of inflammation). This very high-risk subgroup of people with prediabetes had incidence rates for ASCVD events and for heart failure that tracked identically to those with type 2 diabetes. However. the incidence rate for CKD in these high-risk people with prediabetes remained below that of patients with type 2 diabetes.
Dr. Honigberg had no disclosures. Dr. Nambi has received research funding from Amgen, Merck, and Roche.
FROM ACC 2021
Single subcutaneous shot offers fast, potent platelet inhibition in STEMI
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.
Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.
The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.
The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.
Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.
“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.
RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.
In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.
The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.
The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).
The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.
“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”
The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.
Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”
The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.
“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.
Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.
CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.
A version of this article first appeared on Medscape.com.
New AHA/ASA guideline on secondary stroke prevention
When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.
“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.
“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.
The updated guideline was published online May 24, 2021, in Stroke.
“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.
The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
Let pathogenic subtype guide prevention
For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.
Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.
“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.
For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.
Among the recommendations:
- Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
- Screen for and initiate anticoagulant drug therapy to reduce recurrent events.
- Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
- Consider or carotid artery stenting for select patients with narrowing of carotid arteries.
- Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
- In some patients, it’s reasonable to consider percutaneous closure of .
The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.
“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.
The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.
“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.
“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.
The updated guideline was published online May 24, 2021, in Stroke.
“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.
The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
Let pathogenic subtype guide prevention
For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.
Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.
“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.
For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.
Among the recommendations:
- Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
- Screen for and initiate anticoagulant drug therapy to reduce recurrent events.
- Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
- Consider or carotid artery stenting for select patients with narrowing of carotid arteries.
- Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
- In some patients, it’s reasonable to consider percutaneous closure of .
The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.
“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.
The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
When possible, diagnostic tests to determine the cause of a first stroke or transient ischemic attack (TIA) should be completed within 48 hours after symptom onset, the American Heart Association/American Stroke Association said in an updated clinical practice guideline.
“It is critically important to understand the best ways to prevent another stroke once someone has had a stroke or a TIA,” Dawn O. Kleindorfer, MD, chair of the guideline writing group, said in a news release.
“If we can pinpoint the cause of the first stroke or TIA, we can tailor strategies to prevent a second stroke,” said Dr. Kleindorfer, professor and chair, department of neurology, University of Michigan, Ann Arbor.
The updated guideline was published online May 24, 2021, in Stroke.
“The secondary prevention of stroke guideline is one of the ASA’s ‘flagship’ guidelines, last updated in 2014,” Dr. Kleindorfer said.
The update includes “a number of changes to the writing and formatting of this guideline to make it easier for professionals to understand and locate information more quickly, ultimately greatly improving patient care and preventing more strokes in our patients,” she noted.
Let pathogenic subtype guide prevention
For patients who have survived a stroke or TIA, management of vascular risk factors, particularly hypertension, diabetes, cholesterol/triglyceride levels, and smoking cessation, are key secondary prevention tactics, the guideline said.
Limiting salt intake and/or following a heart-healthy Mediterranean diet is also advised, as is engaging in at least moderate-intensity aerobic activity for at least 10 minutes four times a week or vigorous-intensity aerobic activity for at least 20 minutes twice a week.
“Approximately 80% of strokes can be prevented by controlling blood pressure, eating a healthy diet, engaging in regular physical activity, not smoking and maintaining a healthy weight,” Amytis Towfighi, MD, vice chair of the guideline writing group and director of neurologic services, Los Angeles County Department of Health Services, noted in the release.
For health care professionals, the guideline said specific recommendations for secondary prevention often depend on the ischemic stroke/TIA subtype. “Therefore, new in this guideline is a section describing recommendations for the diagnostic workup after ischemic stroke, to define ischemic stroke pathogenesis (when possible), and to identify targets for treatment to reduce the risk of recurrent ischemic stroke. Recommendations are now segregated by pathogenetic subtype,” the guideline stated.
Among the recommendations:
- Use multidisciplinary care teams to personalize care for patients and employ shared decision-making with the patient to develop care plans that incorporate a patient’s wishes, goals, and concerns.
- Screen for and initiate anticoagulant drug therapy to reduce recurrent events.
- Prescribe antithrombotic therapy, including antiplatelets or anticoagulants, in the absence of contraindications. The guideline noted that the combination of antiplatelets and anticoagulation is typically not recommended for preventing second strokes and that dual antiplatelet therapy (DAPT) – taking along with a second medication to prevent blood clotting – is recommended in the short term and only for specific patients: those with early arriving minor stroke and high-risk TIA or severe symptomatic stenosis.
- Consider or carotid artery stenting for select patients with narrowing of carotid arteries.
- Aggressive medical management of risk factors and short-term DAPT are preferred for patients with severe intracranial stenosis thought to be the cause of first stroke or TIA.
- In some patients, it’s reasonable to consider percutaneous closure of .
The guideline is accompanied by a systematic review and meta-analysis regarding the benefits and risks of dual antiplatelet versus single antiplatelet therapy for secondary stroke prevention. The authors conclude that DAPT may be appropriate for select patients.
“Additional research is needed to determine: the optimal timing of starting treatment relative to the clinical event; the optimal duration of DAPT to maximize the risk-benefit ratio; whether additional populations excluded from POINT and CHANCE [two of the trials examined], such as those with major stroke, may also benefit from early DAPT; and whether certain genetic profiles eliminate the benefit of early DAPT,” concluded the reviewers, led by Devin Brown, MD, University of Michigan.
The guideline was prepared on behalf of and approved by the AHA Stroke Council’s Scientific Statements Oversight Committee on Clinical Practice Guidelines. The writing group included representatives from the AHA/ASA and the American Academy of Neurology. The guideline has been endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons and the Society of Vascular and Interventional Neurology. It has also been affirmed by the AAN as an educational tool for neurologists.
The research had no commercial funding.
A version of this article first appeared on Medscape.com.
Large vessel stroke linked to AstraZeneca COVID vaccine
The three cases (one of which was fatal) occurred in two women and one man in their 30s or 40s and involved blockages of the carotid and middle cerebral artery. Two of the three patients also had venous thrombosis involving the portal and cerebral venous system. All three also had extremely low platelet counts, confirmed antibodies to platelet factor 4, and raised D-dimer levels, all characteristic of the vaccine-induced immune thrombotic thrombocytopenia (VITT) reaction associated with the AstraZeneca vaccine.
They are described in detail in a letter published online on May 25 in the Journal of Neurology, Neurosurgery & Psychiatry
“These are [the] first detailed reports of arterial stroke believed to be caused by VITT after the AstraZeneca COVID vaccine, although stroke has been mentioned previously in the VITT data,” said senior author David Werring, PhD, FRCP.
“VITT has more commonly presented as CVST [Cerebral venous sinus thrombosis] which is stroke caused by a venous thrombosis; these cases are showing that it can also cause stroke caused by an arterial thrombosis,” explained Dr. Werring, professor of clinical neurology at the Stroke Research Centre, University College London.
“In patients who present with ischemic stroke, especially younger patients, and who have had the AstraZeneca vaccine within the past month, clinicians need to consider VITT as a possible cause, as there is a specific treatment needed for this syndrome,” he said.
Young patients presenting with ischemic stroke after receiving the AstraZeneca vaccine should urgently be evaluated for VITT with laboratory tests, including platelet count, D-dimers, fibrinogen, and anti-PF4 antibodies, the authors wrote, and then managed by a multidisciplinary team, including hematology, neurology, stroke, neurosurgery, and neuroradiology, for rapid access to treatments including intravenous immune globulin, methylprednisolone, plasmapheresis, and nonheparin anticoagulants such as fondaparinux, argatroban, or direct oral anticoagulants.
Dr. Werring noted that these reports do not add anything to the overall risk/benefit of the vaccine, as they are only describing three cases. “While VITT is very serious, the benefit of the vaccine still outweighs its risks,” he said. “Around 40% of patients hospitalized with COVID-19 experience some sort of thrombosis and about 1.5% have an ischemic stroke. Whereas latest figures from the U.K. estimate the incidence of VITT with the AstraZeneca vaccine of 1 in 50,000 to 1 in 100,000.
“Our report doesn’t suggest that VITT is more common than these latest figures estimate, but we are just drawing attention to an alternative presentation,” he added.
Three cases
The first patient in the current case series, a woman in her 30s, experienced an intermittent headache on the right side and around her eyes 6 days after the vaccine. Five days later, she awoke feeling drowsy and with weakness to her left face, arm, and leg.
Imaging revealed a blocked right middle cerebral artery with brain infarction and clots in the right portal vein. She underwent brain surgery to reduce the pressure in her skull, plasma removal and replacement, and received the anticoagulant fondaparinux, but she still unfortunately died.
The second patient, a woman in her late 30s, presented with headache, confusion, weakness in her left arm, and loss of vision on the left side 12 days after having received the vaccine. Imaging showed occlusion of both carotid arteries, as well as pulmonary embolism and a left cerebral venous sinus thrombosis.
Her platelet count increased following plasma removal and replacement and intravenous corticosteroids, and her condition improved after fondaparinux treatment.
The third patient, a man in his early 40s, presented 3 weeks after receiving his vaccination with problems speaking. Imaging showed a clot in the left middle cerebral artery, but there was no evidence of clots in the cerebral venous sinuses. He received a platelet and plasma transfusion, and fondaparinux, and remains stable.
High index of suspicion required
In a linked commentary, Hugh Markus, PhD, FRCP, professor of stroke medicine at the University of Cambridge, United Kingdom, wrote: “This report emphasizes that the immune mediated coagulopathy can also cause arterial thrombosis, including ischemic stroke, although venous thrombosis and especially cerebral venous sinus thrombosis appear more frequent.
“During the current period of COVID vaccination, a high index of suspicion is required to identify thrombotic episodes following vaccination,” he added. “However, it is important to remember that these side effects are rare and much less common than both cerebral venous thrombosis and ischemic stroke associated with COVID-19 infection itself.”
Risk/benefit unaltered
Several experts who commented on these reports for the Science Media Centre all agreed with Dr. Werring and Dr. Markus that these reports do not alter the current risk/benefit estimates with the vaccine.
Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, who sits on the U.K.’s Medicines and Healthcare Products Regulatory Agency’s Pharmacovigilance Expert Advisory Group, said: “The picture regarding the rare syndrome of blood clots combined with low platelet counts associated with the AstraZeneca vaccine is becoming clearer. Until now, the cases described have tended to involve clots in veins such as cerebral vein thrombosis. In this series of three case reports, we now have some evidence that the types of blood vessels affected include arteries as well as veins.”
“It’s important to stress that such cases remain very rare, and it’s certainly much rarer in people who have had the AstraZeneca vaccine than it is in people affected by COVID-19 itself,” Dr. Douglas emphasized.
“The description of the cases suggests the patients involved presented with the same kind of symptoms as already described in cases involving cerebral vein thrombosis, and they don’t suggest patients need to be on the alert for anything different,” he added.
“However, the emergence of details like this will help guide health professionals who may be faced with similar cases in future; the sooner such cases are recognized, the more chance they will quickly receive the right kind of treatment, hopefully leading to better outcomes.”
Will Lester, MBChB, PhD, consultant hematologist, University Hospitals Birmingham NHS Foundation Trust, said: “VITT remains a rare complication, and patients with a history of thrombosis, including stroke, should not consider themselves to be at any higher risk of this type of rare thrombosis after vaccination, and COVID infection itself is a significant risk for stroke and other types of thrombosis.”
Many countries have paused use of the AstraZeneca vaccine because of its link to the VITT syndrome or restricted its use to older people as the VITT reaction appears to be slightly more common in younger people. In the United Kingdom, the current recommendation is that individuals under 40 years of age should be offered an alternative to the AstraZeneca vaccine where possible.
A version of this article first appeared on Medscape.com.
The three cases (one of which was fatal) occurred in two women and one man in their 30s or 40s and involved blockages of the carotid and middle cerebral artery. Two of the three patients also had venous thrombosis involving the portal and cerebral venous system. All three also had extremely low platelet counts, confirmed antibodies to platelet factor 4, and raised D-dimer levels, all characteristic of the vaccine-induced immune thrombotic thrombocytopenia (VITT) reaction associated with the AstraZeneca vaccine.
They are described in detail in a letter published online on May 25 in the Journal of Neurology, Neurosurgery & Psychiatry
“These are [the] first detailed reports of arterial stroke believed to be caused by VITT after the AstraZeneca COVID vaccine, although stroke has been mentioned previously in the VITT data,” said senior author David Werring, PhD, FRCP.
“VITT has more commonly presented as CVST [Cerebral venous sinus thrombosis] which is stroke caused by a venous thrombosis; these cases are showing that it can also cause stroke caused by an arterial thrombosis,” explained Dr. Werring, professor of clinical neurology at the Stroke Research Centre, University College London.
“In patients who present with ischemic stroke, especially younger patients, and who have had the AstraZeneca vaccine within the past month, clinicians need to consider VITT as a possible cause, as there is a specific treatment needed for this syndrome,” he said.
Young patients presenting with ischemic stroke after receiving the AstraZeneca vaccine should urgently be evaluated for VITT with laboratory tests, including platelet count, D-dimers, fibrinogen, and anti-PF4 antibodies, the authors wrote, and then managed by a multidisciplinary team, including hematology, neurology, stroke, neurosurgery, and neuroradiology, for rapid access to treatments including intravenous immune globulin, methylprednisolone, plasmapheresis, and nonheparin anticoagulants such as fondaparinux, argatroban, or direct oral anticoagulants.
Dr. Werring noted that these reports do not add anything to the overall risk/benefit of the vaccine, as they are only describing three cases. “While VITT is very serious, the benefit of the vaccine still outweighs its risks,” he said. “Around 40% of patients hospitalized with COVID-19 experience some sort of thrombosis and about 1.5% have an ischemic stroke. Whereas latest figures from the U.K. estimate the incidence of VITT with the AstraZeneca vaccine of 1 in 50,000 to 1 in 100,000.
“Our report doesn’t suggest that VITT is more common than these latest figures estimate, but we are just drawing attention to an alternative presentation,” he added.
Three cases
The first patient in the current case series, a woman in her 30s, experienced an intermittent headache on the right side and around her eyes 6 days after the vaccine. Five days later, she awoke feeling drowsy and with weakness to her left face, arm, and leg.
Imaging revealed a blocked right middle cerebral artery with brain infarction and clots in the right portal vein. She underwent brain surgery to reduce the pressure in her skull, plasma removal and replacement, and received the anticoagulant fondaparinux, but she still unfortunately died.
The second patient, a woman in her late 30s, presented with headache, confusion, weakness in her left arm, and loss of vision on the left side 12 days after having received the vaccine. Imaging showed occlusion of both carotid arteries, as well as pulmonary embolism and a left cerebral venous sinus thrombosis.
Her platelet count increased following plasma removal and replacement and intravenous corticosteroids, and her condition improved after fondaparinux treatment.
The third patient, a man in his early 40s, presented 3 weeks after receiving his vaccination with problems speaking. Imaging showed a clot in the left middle cerebral artery, but there was no evidence of clots in the cerebral venous sinuses. He received a platelet and plasma transfusion, and fondaparinux, and remains stable.
High index of suspicion required
In a linked commentary, Hugh Markus, PhD, FRCP, professor of stroke medicine at the University of Cambridge, United Kingdom, wrote: “This report emphasizes that the immune mediated coagulopathy can also cause arterial thrombosis, including ischemic stroke, although venous thrombosis and especially cerebral venous sinus thrombosis appear more frequent.
“During the current period of COVID vaccination, a high index of suspicion is required to identify thrombotic episodes following vaccination,” he added. “However, it is important to remember that these side effects are rare and much less common than both cerebral venous thrombosis and ischemic stroke associated with COVID-19 infection itself.”
Risk/benefit unaltered
Several experts who commented on these reports for the Science Media Centre all agreed with Dr. Werring and Dr. Markus that these reports do not alter the current risk/benefit estimates with the vaccine.
Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, who sits on the U.K.’s Medicines and Healthcare Products Regulatory Agency’s Pharmacovigilance Expert Advisory Group, said: “The picture regarding the rare syndrome of blood clots combined with low platelet counts associated with the AstraZeneca vaccine is becoming clearer. Until now, the cases described have tended to involve clots in veins such as cerebral vein thrombosis. In this series of three case reports, we now have some evidence that the types of blood vessels affected include arteries as well as veins.”
“It’s important to stress that such cases remain very rare, and it’s certainly much rarer in people who have had the AstraZeneca vaccine than it is in people affected by COVID-19 itself,” Dr. Douglas emphasized.
“The description of the cases suggests the patients involved presented with the same kind of symptoms as already described in cases involving cerebral vein thrombosis, and they don’t suggest patients need to be on the alert for anything different,” he added.
“However, the emergence of details like this will help guide health professionals who may be faced with similar cases in future; the sooner such cases are recognized, the more chance they will quickly receive the right kind of treatment, hopefully leading to better outcomes.”
Will Lester, MBChB, PhD, consultant hematologist, University Hospitals Birmingham NHS Foundation Trust, said: “VITT remains a rare complication, and patients with a history of thrombosis, including stroke, should not consider themselves to be at any higher risk of this type of rare thrombosis after vaccination, and COVID infection itself is a significant risk for stroke and other types of thrombosis.”
Many countries have paused use of the AstraZeneca vaccine because of its link to the VITT syndrome or restricted its use to older people as the VITT reaction appears to be slightly more common in younger people. In the United Kingdom, the current recommendation is that individuals under 40 years of age should be offered an alternative to the AstraZeneca vaccine where possible.
A version of this article first appeared on Medscape.com.
The three cases (one of which was fatal) occurred in two women and one man in their 30s or 40s and involved blockages of the carotid and middle cerebral artery. Two of the three patients also had venous thrombosis involving the portal and cerebral venous system. All three also had extremely low platelet counts, confirmed antibodies to platelet factor 4, and raised D-dimer levels, all characteristic of the vaccine-induced immune thrombotic thrombocytopenia (VITT) reaction associated with the AstraZeneca vaccine.
They are described in detail in a letter published online on May 25 in the Journal of Neurology, Neurosurgery & Psychiatry
“These are [the] first detailed reports of arterial stroke believed to be caused by VITT after the AstraZeneca COVID vaccine, although stroke has been mentioned previously in the VITT data,” said senior author David Werring, PhD, FRCP.
“VITT has more commonly presented as CVST [Cerebral venous sinus thrombosis] which is stroke caused by a venous thrombosis; these cases are showing that it can also cause stroke caused by an arterial thrombosis,” explained Dr. Werring, professor of clinical neurology at the Stroke Research Centre, University College London.
“In patients who present with ischemic stroke, especially younger patients, and who have had the AstraZeneca vaccine within the past month, clinicians need to consider VITT as a possible cause, as there is a specific treatment needed for this syndrome,” he said.
Young patients presenting with ischemic stroke after receiving the AstraZeneca vaccine should urgently be evaluated for VITT with laboratory tests, including platelet count, D-dimers, fibrinogen, and anti-PF4 antibodies, the authors wrote, and then managed by a multidisciplinary team, including hematology, neurology, stroke, neurosurgery, and neuroradiology, for rapid access to treatments including intravenous immune globulin, methylprednisolone, plasmapheresis, and nonheparin anticoagulants such as fondaparinux, argatroban, or direct oral anticoagulants.
Dr. Werring noted that these reports do not add anything to the overall risk/benefit of the vaccine, as they are only describing three cases. “While VITT is very serious, the benefit of the vaccine still outweighs its risks,” he said. “Around 40% of patients hospitalized with COVID-19 experience some sort of thrombosis and about 1.5% have an ischemic stroke. Whereas latest figures from the U.K. estimate the incidence of VITT with the AstraZeneca vaccine of 1 in 50,000 to 1 in 100,000.
“Our report doesn’t suggest that VITT is more common than these latest figures estimate, but we are just drawing attention to an alternative presentation,” he added.
Three cases
The first patient in the current case series, a woman in her 30s, experienced an intermittent headache on the right side and around her eyes 6 days after the vaccine. Five days later, she awoke feeling drowsy and with weakness to her left face, arm, and leg.
Imaging revealed a blocked right middle cerebral artery with brain infarction and clots in the right portal vein. She underwent brain surgery to reduce the pressure in her skull, plasma removal and replacement, and received the anticoagulant fondaparinux, but she still unfortunately died.
The second patient, a woman in her late 30s, presented with headache, confusion, weakness in her left arm, and loss of vision on the left side 12 days after having received the vaccine. Imaging showed occlusion of both carotid arteries, as well as pulmonary embolism and a left cerebral venous sinus thrombosis.
Her platelet count increased following plasma removal and replacement and intravenous corticosteroids, and her condition improved after fondaparinux treatment.
The third patient, a man in his early 40s, presented 3 weeks after receiving his vaccination with problems speaking. Imaging showed a clot in the left middle cerebral artery, but there was no evidence of clots in the cerebral venous sinuses. He received a platelet and plasma transfusion, and fondaparinux, and remains stable.
High index of suspicion required
In a linked commentary, Hugh Markus, PhD, FRCP, professor of stroke medicine at the University of Cambridge, United Kingdom, wrote: “This report emphasizes that the immune mediated coagulopathy can also cause arterial thrombosis, including ischemic stroke, although venous thrombosis and especially cerebral venous sinus thrombosis appear more frequent.
“During the current period of COVID vaccination, a high index of suspicion is required to identify thrombotic episodes following vaccination,” he added. “However, it is important to remember that these side effects are rare and much less common than both cerebral venous thrombosis and ischemic stroke associated with COVID-19 infection itself.”
Risk/benefit unaltered
Several experts who commented on these reports for the Science Media Centre all agreed with Dr. Werring and Dr. Markus that these reports do not alter the current risk/benefit estimates with the vaccine.
Ian Douglas, PhD, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, who sits on the U.K.’s Medicines and Healthcare Products Regulatory Agency’s Pharmacovigilance Expert Advisory Group, said: “The picture regarding the rare syndrome of blood clots combined with low platelet counts associated with the AstraZeneca vaccine is becoming clearer. Until now, the cases described have tended to involve clots in veins such as cerebral vein thrombosis. In this series of three case reports, we now have some evidence that the types of blood vessels affected include arteries as well as veins.”
“It’s important to stress that such cases remain very rare, and it’s certainly much rarer in people who have had the AstraZeneca vaccine than it is in people affected by COVID-19 itself,” Dr. Douglas emphasized.
“The description of the cases suggests the patients involved presented with the same kind of symptoms as already described in cases involving cerebral vein thrombosis, and they don’t suggest patients need to be on the alert for anything different,” he added.
“However, the emergence of details like this will help guide health professionals who may be faced with similar cases in future; the sooner such cases are recognized, the more chance they will quickly receive the right kind of treatment, hopefully leading to better outcomes.”
Will Lester, MBChB, PhD, consultant hematologist, University Hospitals Birmingham NHS Foundation Trust, said: “VITT remains a rare complication, and patients with a history of thrombosis, including stroke, should not consider themselves to be at any higher risk of this type of rare thrombosis after vaccination, and COVID infection itself is a significant risk for stroke and other types of thrombosis.”
Many countries have paused use of the AstraZeneca vaccine because of its link to the VITT syndrome or restricted its use to older people as the VITT reaction appears to be slightly more common in younger people. In the United Kingdom, the current recommendation is that individuals under 40 years of age should be offered an alternative to the AstraZeneca vaccine where possible.
A version of this article first appeared on Medscape.com.
Final SPRINT data confirm lower BP is better
The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.
The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.
Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.
For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).
In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.
All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.
“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.
She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.
“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.
“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.
After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.
“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.
In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
Manageable risk
The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.
As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”
“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.
Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.
“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.
“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.
“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.
The potential adverse effects of intensive blood pressure control are “very manageable,” he added.
Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.
The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.
Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.
For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).
In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.
All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.
“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.
She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.
“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.
“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.
After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.
“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.
In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
Manageable risk
The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.
As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”
“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.
Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.
“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.
“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.
“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.
The potential adverse effects of intensive blood pressure control are “very manageable,” he added.
Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The results include data on some outcome events from the trial that had yet to be adjudicated when the primary analysis was released in 2015, as well as posttrial observational follow-up data collected through July 2016.
The data confirm and enhance the earlier findings and show that “lower is better” when it comes to blood pressure, primary investigator Cora E. Lewis, MD, professor and chair, department of epidemiology, University of Alabama at Birmingham, said in an interview.
Final results of the Systolic Blood Pressure Intervention Trial (SPRINT) were published in the May 20 issue of the New England Journal of Medicine.
For the trial, researchers enrolled 9,361 adults 50 years and older with a SBP between 130 and 180 mm Hg who were at increased risk for cardiovascular disease (CVD) but did not have a history of diabetes or stroke. Patients were randomly assigned to an intensive treatment target (SBP < 120 mm Hg) or a standard treatment target (SBP < 140 mm Hg).
In the final analysis, the rate of the primary outcome was 1.77% per year in the intensive-treatment group and 2.40% per year in the standard-treatment group (hazard ratio [HR], 0.73; 95% confidence interval [CR], 0.63-0.86; P < .001), similar to the earlier SPRINT findings.
All-cause mortality was 1.06% per year in the intensive-treatment group and 1.41% per year in the standard-treatment group (HR, 0.75; 95% CI, 0.61-0.92; P = .006), again similar to the previous findings.
“These results were highly statistically significant. It is remarkable in a trial powered for a composite CVD outcome to obtain a significant benefit for total mortality,” Dr. Lewis said.
She noted that one criticism of the initial SPRINT results was that, for the components of the primary outcome, only heart failure and death due to CVD were significantly lower in the intensively treated group.
“Heart failure can be difficult to diagnose from records in a clinical trial, and the critiques were that this was shaky evidence, given that more participants treated to less than 120 were on diuretics, which could decrease swelling, a key symptom of heart failure,” she explained.
“In these final results, SPRINT found that risk of myocardial infarction, heart failure, and death from CVD were significantly lower in the group treated to less than 120, and risk of the primary outcome, excluding heart failure, was still significantly lower in the more intensively treated group,” she noted.
After the trial phase ended, blood pressure treatment was returned to the participants’ usual source of medical care and the trial treatment goals were no longer pursued. SPRINT continued to collect data on the outcomes through July 2016. During this time, SBP rose 6.9 mm Hg in the intensive-treatment group and 2.6 mm Hg in the standard-treatment group.
“Putting all the data together from the trial phase and the phase after randomized interventions had been stopped, there was still a significant benefit for the more intensive treatment on the primary outcome and on death from all causes,” Dr. Lewis said.
In addition, a separate new analysis based on all the data showed significantly fewer first and recurrent primary outcome events with intensive treatment than with standard treatment (435 vs. 552; HR, 0.78; 95% CI, 0.69-0.89; P < .001).
Manageable risk
The pattern of safety events in the final analysis was similar to the 2015 report. In the intervention period, rates of serious adverse events overall did not differ significantly between the groups. However, rates of hypotension, electrolyte abnormalities, syncope (none leading to injurious falls), and acute kidney injury were higher in the intensive-treatment group.
As in other SPRINT reports, “acute kidney injury safety events were generally mild and there was nearly complete recovery of kidney function within 1 year,” Dr. Lewis said. “This and other analyses we have published indicate this is probably a hemodynamic effect.”
“Intensive treatment can be well tolerated and is generally safe with proper patient selection and monitoring. There are advantages to intensive therapy, and some risks, but I don’t think the risks are such that we should just throw the idea of more intensive treatment out the window,” Dr. Lewis said.
Reached for comment, Carlos G. Santos-Gallego, MD, from the Icahn School of Medicine at Mount Sinai in New York, said there has been “controversy” over whether intensive blood pressure control targeting systolic to below 120 mm Hg is beneficial.
“The original SPRINT trial is incredibly important, in that it conclusively demonstrated that among patients with hypertension and increased cardiovascular risk, targeting systolic blood pressure to below 120 mm Hg resulted in lower rates of adverse cardiovascular events and, importantly, all-cause mortality," compared with the conventional target of 140 mm Hg, he said in an interview.
“This final report of the SPRINT trial basically consolidates, confirms, and corroborates the original SPRINT data,” he noted. However, the final data are “more robust, with additional primary outcome events and all events having been adjudicated by a central committee, and there is an additional observation period of 1 extra year in which the treatment has been discontinued,” he said.
“Over time, we are becoming more and more certain that lower is better with blood pressure. We still have a long way to go, but the cardiology community is slowly becoming more intense in our treatment of blood pressure for our patients,” Dr. Santos-Gallego said.
The potential adverse effects of intensive blood pressure control are “very manageable,” he added.
Support for SPRINT was provided by the National Institutes of Health. Full disclosures for authors are available in the original article. Dr. Santos-Gallego has no relevant disclosures.
A version of this article first appeared on Medscape.com.
LAAOS III: Surgical LAA closure cuts AFib stroke risk by one third
Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).
At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).
In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.
The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.
The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.
“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA2DS2-VASc score – the appendage should come off,” he said in an interview.
Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).
Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”
Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.
Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.
“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.
The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”
In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.
“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”
Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.
“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”
Global, nonindustry effort
LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA2DS2-VASc score of at least 2.
In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.
Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.
The mean CHA2DS2-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.
Operative outcomes in the LAAO and no-LAAO groups were as follows:
- Bypass time: mean, 119 minutes vs. 113 minutes.
- Cross-clamp time: mean, 86 minutes vs. 82 minutes.
- Chest tube output: median, 520 mL vs. 500 mL.
- Reoperation for bleeding: both, 4.0%.
- Prolonged hospitalization due to HF: 5 vs. 14 events.
- 30-day mortality: 3.7% vs 4.0%.
The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.
“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”
Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).
In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”
The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA2DS2-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.
Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.
Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.
The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
A version of this article first appeared on Medscape.com.
Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).
At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).
In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.
The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.
The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.
“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA2DS2-VASc score – the appendage should come off,” he said in an interview.
Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).
Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”
Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.
Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.
“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.
The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”
In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.
“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”
Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.
“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”
Global, nonindustry effort
LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA2DS2-VASc score of at least 2.
In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.
Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.
The mean CHA2DS2-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.
Operative outcomes in the LAAO and no-LAAO groups were as follows:
- Bypass time: mean, 119 minutes vs. 113 minutes.
- Cross-clamp time: mean, 86 minutes vs. 82 minutes.
- Chest tube output: median, 520 mL vs. 500 mL.
- Reoperation for bleeding: both, 4.0%.
- Prolonged hospitalization due to HF: 5 vs. 14 events.
- 30-day mortality: 3.7% vs 4.0%.
The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.
“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”
Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).
In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”
The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA2DS2-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.
Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.
Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.
The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
A version of this article first appeared on Medscape.com.
Left atrial appendage occlusion performed at the time of other heart surgery reduces the risk for stroke by about one-third in high-risk patients with atrial fibrillation (AFib), according to results of the Left Atrial Appendage Occlusion Study III (LAAOS III).
At 3.8 years’ follow-up, the primary endpoint of ischemic stroke or systemic embolism occurred in 4.8% of patients randomly assigned to left atrial appendage occlusion (LAAO) and 7.0% of those with no occlusion. This translated into a 33% relative risk reduction (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .001).
In a landmark analysis, the effect was present early on but was more pronounced after the first 30 days, reducing the relative risk by 42% (HR, 0.58; 95% CI, 0.42-0.80), the researchers report.
The reduction in ongoing stroke risk was on top of oral anticoagulation (OAC) and consistent across all subgroups, Richard Whitlock, MD, PhD, professor of surgery, McMaster University, Hamilton, Ont., reported in a late-breaking trial session at the annual scientific sessions of the American College of Cardiology.
The procedure was safe and added, on average, just 6 minutes to cardiopulmonary bypass time, according to the results, simultaneously published in the New England Journal of Medicine.
“Any patient who comes to the operating room who fits the profile of a LAAOS III patient – so has atrial fibrillation and an elevated stroke risk based on their CHA2DS2-VASc score – the appendage should come off,” he said in an interview.
Commenting during the formal discussion, panelist Michael J. Mack, MD, of Baylor Health Care System in Houston, said, “This is potentially a game-changing, practice-changing study” but asked if there are any patients who shouldn’t undergo LAAO, such as those with heart failure (HF).
Dr. Whitlock said about 10%-15% of patients coming for heart surgery have a history of AFib and “as surgeons, you do need to individualize therapy. If you have a very frail patient, have concerns about tissue quality, you really need to think about how you would occlude the left atrial appendage or if you would occlude.”
Reassuringly, he noted, the data show no increase in HF hospitalizations and a beneficial effect on stroke among patients with HF and those with low ejection fractions, below 50%.
Observational data on surgical occlusion have been inconsistent, and current guidelines offer a weak recommendation in patients with AFib who have a contraindication to long-term anticoagulation. This is the first study to definitively prove that ischemic stroke is reduced by managing the left atrial appendage, he said in an interview.
“The previous percutaneous trials failed to demonstrate that; they demonstrated noninferiority but it was driven primarily by the avoidance of hemorrhagic events or strokes through taking patients off oral anticoagulation,” he said.
The results should translate into a class I guideline recommendation, he added. “This opens up a new paradigm of treatment for atrial fibrillation and stroke prevention in that it is really the first study that has looked at the additive effects of managing the left atrial appendage in addition to oral anticoagulation, and it’s protective on top of oral anticoagulation. That is a paradigm shift.”
In an accompanying editorial, Richard L. Page, MD, University of Vermont in Burlington, said the trial provides no insight on the possible benefit of surgical occlusion in patients unable to receive anticoagulation or with a lower CHA2DS2-VASc score, but he agreed a class I recommendation is likely for the population studied.
“I hope and anticipate that the results of this paper will strengthen the guideline indications for surgical left atrial appendage occlusion and will increase the number of cardiac surgeons who routinely perform this add-on procedure,” he said. “While many already perform this procedure, cardiac surgeons should now feel more comfortable that surgical left atrial appendage occlusion is indicated and supported by high-quality randomized data.”
Unfortunately, LAAOS III does not answer the question of whether patients can come off anticoagulation, but it does show surgical occlusion provides added protection from strokes, which can be huge with atrial fibrillation, Dr. Whitlock said.
“I spoke with a patient today who is an active 66-year-old individual on a [direct oral anticoagulant], and his stroke risk has been further reduced by 30%-40%, so he was ecstatic to hear the results,” Dr. Whitlock said. “I think it’s peace of mind.”
Global, nonindustry effort
LAAOS III investigators at 105 centers in 27 countries enrolled 4,811 patients undergoing cardiac surgery (mean age, 71 years; 68% male) who had a CHA2DS2-VASc score of at least 2.
In all, 4,770 were randomly assigned to no LAAO or occlusion via the preferred technique of amputation with suture closure of the stump as well as stapler occlusion, or epicardial device closure with the AtriClip (AtriCure) or TigerPaw (Maquet Medical). The treating team, researchers, and patients were blinded to assignment.
Patients were followed every 6 months with a validated stroke questionnaire. The trial was stopped early by the data safety monitoring board after the second interim analysis.
The mean CHA2DS2-VASc score was 4.2, one-third of patients had permanent AFib, 9% had a history of stroke, and more than two-thirds underwent a valve procedure, which makes LAAOS III unique, as many previous trials excluded valvular AFib, Dr. Whitlock pointed out.
Operative outcomes in the LAAO and no-LAAO groups were as follows:
- Bypass time: mean, 119 minutes vs. 113 minutes.
- Cross-clamp time: mean, 86 minutes vs. 82 minutes.
- Chest tube output: median, 520 mL vs. 500 mL.
- Reoperation for bleeding: both, 4.0%.
- Prolonged hospitalization due to HF: 5 vs. 14 events.
- 30-day mortality: 3.7% vs 4.0%.
The primary safety outcome of HF hospitalization at 3.8 years occurred in 7.7% of patients with LAAO and 6.8% without occlusion (HR, 1.13; 95% CI, 0.92-1.40), despite concerns that taking off the appendage could worsen HF risk by impairing renal clearance of salt and water.
“There’s observational data on either side of the fence, so it was an important endpoint that people were concerned about,” Dr. Whitlock told this news organization. “We had a data collection firm dedicated to admission for heart failure to really tease that out and, in the end, we saw no adverse effect.”
Although rates of ischemic stroke at 3.8 years were lower with LAAO than without (4.2% vs. 6.6%; HR, 0.62; 95% CI, 0.48-0.80), there was no difference in systemic embolism (0.3% for both) or death (22.6% vs. 22.5%).
In LAAOS III, fewer than 2% of the deaths were attributed to stroke, which is consistent with large stroke registries, Dr. Whitlock said. “Stroke is not what causes people with atrial fibrillation to die; it’s actually the progression on to heart failure.”
The positive effect on stroke was consistent across all subgroups, including sex, age, rheumatic heart disease, type of OAC at baseline, CHA2DS2-VASc score (≤4 vs. >4), type of surgery, history of heart failure or hypertension, and prior stroke/transient ischemic attack/systemic embolism.
Panelist Anne B. Curtis, MD, State University of New York at Buffalo, expressed surprise that about half of patients at baseline were not receiving anticoagulation and questioned whether event rates varied among those who did and didn’t stay on OAC.
Dr. Whitlock noted that OAC is often underused in AFib and that analyses showed the effects were consistent whether patients were on or off anticoagulants.
The study was sponsored by the Population Health Research Institute, McMaster University. Dr. Whitlock reported no relevant disclosures. Dr. Curtis reported consultant fees/honoraria from Abbott, Janssen, Medtronic, Milestone Pharmaceuticals, and Sanofi Aventis, and data safety monitoring board participation for Medtronic.
A version of this article first appeared on Medscape.com.
FROM ACC 2021
ADAPTABLE: Low-dose aspirin as good as high-dose in CHD?
No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.
Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.
“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.
The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.
Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.
He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”
Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”
Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”
“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.
Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.
“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.
He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.
The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.
After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).
The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).
“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”
He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”
Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).
“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”
“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”
A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
Innovative study design
The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.
Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal.
Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.
“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented.
He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.
“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”
He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.”
Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.
They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.
‘Pioneering’ trial
Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.
Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”
Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”
On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”
But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.
Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.
Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.
In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.
But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.
“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.
He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.
But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.
The trial was supported by an award from the Patient-Centred Outcomes Research Institute. Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
A version of this article first appeared on Medscape.com.
No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.
Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.
“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.
The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.
Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.
He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”
Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”
Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”
“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.
Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.
“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.
He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.
The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.
After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).
The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).
“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”
He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”
Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).
“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”
“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”
A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
Innovative study design
The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.
Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal.
Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.
“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented.
He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.
“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”
He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.”
Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.
They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.
‘Pioneering’ trial
Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.
Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”
Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”
On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”
But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.
Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.
Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.
In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.
But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.
“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.
He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.
But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.
The trial was supported by an award from the Patient-Centred Outcomes Research Institute. Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
A version of this article first appeared on Medscape.com.
No significant difference in cardiovascular events or major bleeding was shown between patients with established coronary heart disease assigned to a daily aspirin dose of 81 mg and those receiving a dose of 325 mg in the 15,000-patient ADAPTABLE trial.
Although substantial dose switching occurred in the trial, particularly from the higher to the lower dose, lead investigator W. Schuyler Jones, MD, believes the results support the use of the 81-mg dose in most patients.
“While we would have liked to see higher adherence to the assigned doses, we think the results of the trial are reliable,” Dr. Jones said in an interview.
The real-world, open-label, pragmatic trial also involved an innovative low-cost design allowing researchers to identify and communicate with eligible patients directly, opening up a new cost-effective method to conduct clinical research going forward.
Dr. Jones, a cardiologist and associate professor of medicine at Duke University Medical Center, Durham, N.C., presented the ADAPTABLE results at the annual scientific sessions of the American College of Cardiology. They were simultaneously published online in the New England Journal of Medicine.
He noted there were mixed signals in the results. “For example, the main intent-to-treat analysis showed a trend to a lower rate of all-cause death in the 81-mg group, but the subgroup of patients who stayed on the 325-mg dose throughout the study had a lower event rate. But overall, there was no difference.”
Dr. Jones said the investigators had the following take-home messages to patients: “If a patient is already taking 81 mg, staying on this dose is probably right given the similar study results for the primary endpoint and that we didn’t find conclusive evidence that 325 mg is better. But for patients who have tolerated 325 mg long term, then they may want to stay on this dose as it may be associated with moderate benefit.”
Dr. Jones pointed out that, overall, patients who switched doses tended to do worse, but he suggested this may have been more to do with underlying reasons for switching rather than the different dose itself. “For example, switching often happens after bleeding or bruising, which can also often preempt an ischemic event, and other illnesses, such as cancer or atrial fibrillation, can also lead patients to change doses.”
“With the caveat that this trial did not include new patients (the vast majority of patients had been taking aspirin previously) the results support the approach of starting new patients on 81 mg, which is what we have been seeing in evolving clinical practice in recent years,” he added.
Dr. Jones explained that the trial set out to answer the simple but important question about the best dose of aspirin in patients with heart disease.
“Aspirin has been established as an appropriate long-term medication for patients with ischemic heart disease since the 1980s, but we really don’t have any good information on the correct dose.
He noted that the U.S. guidelines suggest any dose in the range of 81 mg to 325 mg daily can be used, whereas the European guidelines recommend 81 mg daily, although this is mainly based on observational data and expert opinion; there is little hard, randomized-trial evidence.
The ADAPTABLE trial randomly assigned 15,076 patients with established heart disease to receive 81 mg or 325 mg of aspirin. Before randomization, 96% of those with available information were already taking aspirin, 85% of whom were taking 81 mg.
After a mean follow-up of 26 months, the primary efficacy endpoint – a composite of all-cause death, myocardial infarction, or stroke – had occurred in 7.28% of the 81-mg group and 7.51% of the 325-mg group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).
The main safety endpoint, hospitalization for major bleeding with an associated blood transfusion, occurred in 0.63% of the 81-mg group and 0.60% of the 325-mg group (HR, 1.18; 95% CI, 0.79-1.77).
“The bleeding safety endpoint looked similar, which may be counterintuitive to what may have been expected,” Dr. Jones commented. “However, the safety endpoint was very stringent. We still haven’t analyzed all the less serious ADR [adverse drug event]/bleeding data, but overall, it does appear to be balanced.”
He added: “Most cardiologists probably may not have expected to see much difference in efficacy between these two doses but would maybe have anticipated a lower bleeding rate with the low dose. I was a little surprised to see such a low bleeding rate in the 325-mg group.”
Patients assigned to 325 mg had a higher incidence of dose switching (41.6%) than those assigned to 81 mg (7.1%) and were more likely to discontinue treatment (11.1% vs. 7.0%). This resulted in fewer median days of exposure to the assigned dose in the 325-mg group (434 vs. 650 days).
“This was an open-label study, and such studies always suffer from a degree of infidelity to the assigned treatment group,” Dr. Jones said. “In ADAPTABLE, this was unbalanced in that a much greater number of patients switched from 325 mg to 81 mg than the other way round.”
“But our results do reflect what happens in normal life,” he added. “People behaved in the study like they do in the real world. They sometimes changed their dose and sometimes stopped taking aspirin altogether. So, I think the results are an accurate representation of the real world.”
A sensitivity analysis based on which dose the patient actually reported taking showed a higher risk for death, MI, or stroke in patients who took 81 mg than those who took 325 mg (HR, 1.25; 95% CI, 1.10-1.43). But as with any postrandomization analysis, this approach has many inherent biases, Dr. Jones cautioned.
Innovative study design
The ADAPTABLE study used an innovative low-cost design, which involved direct communication with the patients themselves.
Using the National Patient-Centered Clinical Research Network (PCORnet), a group of 40 U.S. centers committed to compiling data in a common format, invitations to enroll in the study were sent to eligible patients identified from medical records. Consent and randomization took place on the patient web portal.
Participants then purchased aspirin at the assigned dose themselves, and all follow-up was done virtually or on the phone, with outcomes ascertained remotely (from patient reports, electronic medical records, and insurance claims) without adjudication.
“This is a pretty neat way to do clinical research, enabling us to conduct a 15,000-patient trial on a very tight budget,” Dr. Jones commented.
He estimated that the trial cost around $18 to $19 million. “No industry funder would have sponsored such a study of aspirin, and a typical trial with this many patients conducted in the traditional way would have cost at least 5 or 10 times more,” he said.
“This is the first time this type of study has been done in the U.S. on such a large scale, and it opens up this method for future research.”
He explained that this design, communicating directly with patients, somewhat limits the questions that can be addressed. “As aspirin is purchased over the counter by patients themselves, this is a question that lent itself to be answered in this way.”
Another innovative design feature was the inclusion of “patient partners,” with one patient nominated by each center to be part of the organization of the trial. “This helped keep the research relevant to what patients care about.
They also helped with the recruitment strategy and communication with participants. I think this is something we need to continue and prioritize in clinical research going forward,” Dr. Jones noted.
‘Pioneering’ trial
Discussants of the study at the ACC presentation congratulated the investigators on conducting such an innovative trial.
Donald Lloyd-Jones, MD, chair of preventive medicine at Northwestern University, Chicago, said, “This is really a pioneering large pragmatic trial, and we’re going to need to see more of these over the next few years. The most important legacy from this trial for me is that you did it, and that you showed us many of the promises and some of the pitfalls of these large pragmatic designs.”
Akshay Desai, MD, associate professor of medicine, Harvard Medical School, Boston, added: “This was an innovative approach to answering an important question for daily clinical practice.”
On the results of the study, Dr. Lloyd-Jones said, “Maybe the outcomes were not too surprising, and I certainly endorse your cautious status quo statement about patients staying on the dose that they are on.”
But he suggested that the bleeding safety outcomes were perhaps a little unexpected, being a little lower in the lower-dose group, and he asked whether there was a sensitivity analysis looking at bleeding on a per protocol basis. Dr. Jones answered that this was planned.
Dr. Desai also raised questions about the “unusual bleeding endpoint,” noting that the rates of bleeding were far lower than would be expected, compared with other clinical trials.
Dr. Jones replied that the bleeding endpoint with blood product transfusion was chosen to allow the researchers to accurately identify these events in claims codes. He said the endpoint probably mirrored the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding classification.
In an editorial accompanying the publication of ADAPTABLE, Colin Baigent, FMedSci, says the study provides proof of principle that large pragmatic randomized trials can be conducted in the United States.
But Dr. Baigent, who is professor of epidemiology and director of the Medical Research Council Population Health Research Unit at the University of Oxford (England), says that the high degree of switching between dosages that occurred during the trial gives rise to some uncertainty about the results.
“Because switching was not likely to have been at random, bias arising from this degree of crossover could have obscured a true difference in efficacy or safety (or both), and moreover it is also not possible to conclude that the lack of any significant difference between the two dose groups implies equivalence of the effects of the doses,” he writes.
He suggests that a pilot study may have identified a preference for the 81-mg dose and allowed methods to facilitate equipoise, such as a run-in period with both doses, and only patients adhering being considered for randomization.
But Dr. Baigent concludes that the ADAPTABLE trial is a “major achievement” in that it paves the way for low-cost randomized trials in the United States, which should allow many more clinical questions to be answered.
The trial was supported by an award from the Patient-Centred Outcomes Research Institute. Dr. Schuyler Jones reports consultant fees/honoraria from Bayer Healthcare and Janssen and research grants from Boehringer Ingelheim, Bristol Myers Squibb, and the Patient-Centered Outcomes Research Institute. Dr. Baigent reports grants from Boehringer Ingelheim, Medical Research Council, British Heart Foundation, and National Institute of Health Research, outside the submitted work.
A version of this article first appeared on Medscape.com.
FROM ACC 2021
High teen BMI linked to stroke risk in young adulthood
High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.
Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.
These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.
“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.
The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.
This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.
In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.
They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.
The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.
Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.
A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.
Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.
When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.
Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.
The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.
Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.
One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.
The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.
High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.
Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.
These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.
“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.
The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.
This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.
In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.
They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.
The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.
Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.
A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.
Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.
When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.
Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.
The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.
Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.
One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.
The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.
High and even high-normal body mass index (BMI) were linked to increased ischemic stroke risk, regardless of whether or not individuals had diabetes.
Overweight and obese adolescent groups in the study had a roughly two- to threefold increased risk of ischemic stroke, which was apparent even before age 30 years in the study that was based on records of Israeli adolescents evaluated prior to mandatory military service.
These findings highlight the importance of treating and preventing high BMI among adolescence, study coauthor Gilad Twig, MD, MPH, PhD, said in a press release.
“Adults who survive stroke earlier in life face poor functional outcomes, which can lead to unemployment, depression and anxiety,” said Dr. Twig, associate professor in the department of military medicine in The Hebrew University in Jerusalem.
The costs of stroke prevention and care, already high, are expected to become even higher as the adolescent obesity prevalence goes up, fueling further increases in stroke rate, Dr. Twig added.
This is believed to be the first study showing that stroke risk is associated with higher BMI values in both men and women, not just men, Dr. Twig and coauthors said in their article, published May 13, 2021 in the journal Stroke. Previous studies assessing the stroke-BMI relationship in adolescents were based on records of Swedish men evaluated during military conscription at age 18.
In the present study, Dr. Twig and coauthors assessed the linkage between adolescent BMI and first stroke event in 1.9 million male and female adolescents in Israel who were evaluated 1 year prior to mandatory military service, between the years of 1985 and 2013.
They cross-referenced that information with stroke events in a national registry to which all hospitals in Israel are required to report.
The adolescents were about 17 years of age on average at the time of evaluation, 58% were male, and 84% were born in Israel. The mean age at the beginning of follow-up for stroke was about 31 years.
Over the follow-up period, investigators identified 1,088 first stroke events, including 921 ischemic and 167 hemorrhagic strokes.
A gradual increase in stroke rate was seen across BMI categories for ischemic strokes, but not so much for hemorrhagic strokes, investigators found.
Hazard ratios for first ischemic stroke event were 1.4 (95% confidence interval, 1.2-1.6) for the high-normal BMI group, 2.0 (95% CI, 1.6-2.4) for the overweight group, and 3.5 (95% CI, 2.8-4.5) for the obese group after adjusting for age and sex at beginning of follow-up, investigators reported.
When the adjusted results were stratified by presence or absence of diabetes, estimates were similar to what was seen in the overall risk model, they added.
Among those young adults who developed ischemic stroke, 43% smoked, 29% had high blood pressure, 17% had diabetes, and 32% had abnormal lipids at the time of diagnosis, the reported data showed.
The clinical and public health implications of these findings could be substantial, since strokes are associated with worse medical and socioeconomic outcomes in younger as compared with older individuals, according to Dr. Twig and coauthors.
Younger individuals with stroke have a higher risk of recurrent stroke, heart attack, long-term care, or death, they said. Moreover, about half of young-adult stroke survivors have poor functional outcomes, and their risk of unemployment and depression/anxiety is higher than in young individuals without stroke.
One limitation of the study is that follow-up BMI data were not available for all participants. As a result, the contribution of obesity to stroke risk over time could not be assessed, and the independent risk of BMI during adolescence could not be determined. In addition, the authors said the study underrepresents orthodox and ultraorthodox Jewish women, as they are not obligated to serve in the Israeli military.
The study authors had no disclosures related to the study, which was supported by a medical corps Israel Defense Forces research grant.
FROM STROKE
FDA class I recall for some Cordis carotid stent systems
Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.
The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.
“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.
To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.
The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.
The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.
The FDA has a complete list of product and lot numbers for the recalled devices on their website.
The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.
Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.
The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.
“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.
To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.
The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.
The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.
The FDA has a complete list of product and lot numbers for the recalled devices on their website.
The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.
Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
Cordis, part of Cardinal Health, has recalled certain lots of its Precise PRO Rx carotid stent system because of a risk of separation of the distal tip of the sheathed delivery system during use.
The Food and Drug Administration has classified this recall as class I, the most serious type, because of the potential for serious injury or death.
“If the device separates during use this may cause serious adverse events such as removal of the separated tip from the carotid artery, embolization distally, or stroke,” noted the recall notice posted on the FDA website.
To date, there have been seven complaints, including five reported injuries, related to this device issue. No deaths have been reported.
The Precise PRO Rx stent system is used in patients with stenotic lesions of the carotid arteries. The system includes a metal (nitinol) self-expanding stent preloaded on a delivery catheter used to place the stent.
The recall covers 7,300 devices made between October 2019 and August 2020 and distributed between Dec. 6, 2019, to Feb. 8, 2021.
The FDA has a complete list of product and lot numbers for the recalled devices on their website.
The company sent an urgent medical device recall letter to all affected customers asking them to check inventories and providing instructions on how to return any recalled product they have on hand.
Health care providers with questions about this recall can contact the company by email at [email protected] or by phone at 786-313-2087.
Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.