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Weight loss surgery linked to lower CV event risk in diabetes
, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.
The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.
At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).
The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.
Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).
In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.
In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.
The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.
The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.
In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.
“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.
“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.
The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.
“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.
The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.
SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.
Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.
Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.
Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.
Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.
Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.
Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.
, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.
The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.
At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).
The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.
Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).
In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.
In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.
The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.
The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.
In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.
“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.
“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.
The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.
“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.
The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.
SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.
, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.
The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.
At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).
The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.
Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).
In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.
In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.
The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.
The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.
In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.
“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.
“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.
The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.
“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.
The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.
SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.
AT THE ESC CONGRESS 2019
Key clinical point: Bariatric surgery may reduce the risk of cardiovascular events in people with type 2 diabetes.
Major finding: Bariatric surgery is associated with a 39% reduction in risk of major cardiovascular events.
Study details: Retrospective cohort study in 13,722 individuals with type 2 diabetes and obesity.
Disclosures: The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.
Source: Aminian A et al. JAMA 2019, September 2. DOI: 10.1001/jama.2019.14231.
Periodic repolarization dynamics may predict ICD outcomes
Those with high marker levels more likely to benefit
A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.
High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).
The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.
Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.
Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.
“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.
Their interest in periodic repolarization dynamics arises from increasing evidence that sympathetic mechanisms play a key role in malignant tachyarrhythmias (J Clin Invest. 2005;115:2305-15). They described periodic repolarization dynamics as a “marker of electric instability,” and noted that previous studies have shown a link between increased periodic repolarization dynamics and sudden cardiac death and adequate ICD interventions.
The study noted that more than 100,000 ICDs are implanted in the EU each year at a cost of €2 billion (U.S. $2.2 billion, Europace. 2017;19[suppl 2] ii1-90), but that a 2016 study showed that prophylactic ICD treatment may only benefit select patient subgroups (N Engl J Med. 2016;375:1221-30). While the EU-CERT-ICD supports primary prophylactic ICD therapy as the standard of care for patients with ischemic or nonischemic cardiomyopathy and reduced left ventricular ejection fraction, the invasive nature of ICD implantation carries with it risk of complications.
In an invited commentary, Sana M. Al-Khatib, MD, of Duke University, Durham, N.C., provided some context in interpreting the substudy results, noting, among other considerations, the study’s observational nature, exclusion of almost 40% of potentially eligible patients, and its omission of data for sudden cardiac death (Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736[19]31956-7).
“Periodic repolarization dynamics are not yet ready for prime time,” Dr. Al-Khatib said. The group’s findings need to be validated by other studies, and a reproducible approach to measuring periodic repolarization dynamics should be established, he said. “Until such results are available, periodic repolarization dynamics are unlikely to gain traction as a test that can be consistently used to select patients for primary prevention of sudden cardiac death with ICDs.”
Dr. Bauer and Dr. Al-Khatib had no relevant financial relationships to disclose.
SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.
Those with high marker levels more likely to benefit
Those with high marker levels more likely to benefit
A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.
High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).
The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.
Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.
Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.
“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.
Their interest in periodic repolarization dynamics arises from increasing evidence that sympathetic mechanisms play a key role in malignant tachyarrhythmias (J Clin Invest. 2005;115:2305-15). They described periodic repolarization dynamics as a “marker of electric instability,” and noted that previous studies have shown a link between increased periodic repolarization dynamics and sudden cardiac death and adequate ICD interventions.
The study noted that more than 100,000 ICDs are implanted in the EU each year at a cost of €2 billion (U.S. $2.2 billion, Europace. 2017;19[suppl 2] ii1-90), but that a 2016 study showed that prophylactic ICD treatment may only benefit select patient subgroups (N Engl J Med. 2016;375:1221-30). While the EU-CERT-ICD supports primary prophylactic ICD therapy as the standard of care for patients with ischemic or nonischemic cardiomyopathy and reduced left ventricular ejection fraction, the invasive nature of ICD implantation carries with it risk of complications.
In an invited commentary, Sana M. Al-Khatib, MD, of Duke University, Durham, N.C., provided some context in interpreting the substudy results, noting, among other considerations, the study’s observational nature, exclusion of almost 40% of potentially eligible patients, and its omission of data for sudden cardiac death (Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736[19]31956-7).
“Periodic repolarization dynamics are not yet ready for prime time,” Dr. Al-Khatib said. The group’s findings need to be validated by other studies, and a reproducible approach to measuring periodic repolarization dynamics should be established, he said. “Until such results are available, periodic repolarization dynamics are unlikely to gain traction as a test that can be consistently used to select patients for primary prevention of sudden cardiac death with ICDs.”
Dr. Bauer and Dr. Al-Khatib had no relevant financial relationships to disclose.
SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.
A novel marker of repolarization may identify patients with cardiomyopathy who would benefit from an implanted cardioverter defibrillator, according to a European research study presented at the annual congress of the European Society of Cardiology and published simultaneously in The Lancet.
High periodic repolarization dynamics were linked to substantial reductions in mortality in a prespecified substudy of the EU-CERT-ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators).
The degree of periodic repolarization dynamics correlated with reductions in mortality in the 1,371 patients, 968 of whom had ICD implantation and 403 of whom were treated conservatively, in the prospective, nonrandomized controlled cohort study conducted at 44 centers in 15 countries within the European Union. At a median follow-up of 2-7 years, the ICD group had a mortality rate of 14%; at a follow-up of 1-2 years, the control group had a mortality rate of 16%, resulting in a 43% overall reduction in mortality for the ICD group.
Low periodic repolarization dynamics were associated with a low reduction in ICD-related death, whereas high periodic repolarization dynamics were linked to substantial reductions in mortality. In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls. Periodic repolarization dynamics also served as reliable predictors of appropriate shocks in patients with ICDs as well as death in controls.
Because of the link between high periodic repolarization dynamics and greater benefits, cardiologists may be able to use the measure as a marker to individualize treatment decisions about the use of ICDs, said Axel Bauer, MD, director of University Hospital for Internal Medicine III, Cardiology and Angiology at Medical University Innsbruck, Austria, and coauthors. “Better patient selection could lead to a reduced number of devices needing to be implanted to save a life.
“Our results should help patients to make decisions about their treatment that take into account individual circumstances and preferences,” the researchers noted.
Their interest in periodic repolarization dynamics arises from increasing evidence that sympathetic mechanisms play a key role in malignant tachyarrhythmias (J Clin Invest. 2005;115:2305-15). They described periodic repolarization dynamics as a “marker of electric instability,” and noted that previous studies have shown a link between increased periodic repolarization dynamics and sudden cardiac death and adequate ICD interventions.
The study noted that more than 100,000 ICDs are implanted in the EU each year at a cost of €2 billion (U.S. $2.2 billion, Europace. 2017;19[suppl 2] ii1-90), but that a 2016 study showed that prophylactic ICD treatment may only benefit select patient subgroups (N Engl J Med. 2016;375:1221-30). While the EU-CERT-ICD supports primary prophylactic ICD therapy as the standard of care for patients with ischemic or nonischemic cardiomyopathy and reduced left ventricular ejection fraction, the invasive nature of ICD implantation carries with it risk of complications.
In an invited commentary, Sana M. Al-Khatib, MD, of Duke University, Durham, N.C., provided some context in interpreting the substudy results, noting, among other considerations, the study’s observational nature, exclusion of almost 40% of potentially eligible patients, and its omission of data for sudden cardiac death (Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736[19]31956-7).
“Periodic repolarization dynamics are not yet ready for prime time,” Dr. Al-Khatib said. The group’s findings need to be validated by other studies, and a reproducible approach to measuring periodic repolarization dynamics should be established, he said. “Until such results are available, periodic repolarization dynamics are unlikely to gain traction as a test that can be consistently used to select patients for primary prevention of sudden cardiac death with ICDs.”
Dr. Bauer and Dr. Al-Khatib had no relevant financial relationships to disclose.
SOURCE: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.
FROM THE ESC CONGRESS 2019
Key clinical point: Periodic repolarization dynamics may guide prophylactic treatment with implantable cardioverter defibrillators.
Major finding: In 199 patients with periodic repolarization dynamics of 7.5% or higher, ICD implantation resulted in a 75% reduction in death, compared with controls.
Study details: Prespecified substudy of 1,371 patients from the European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators (EU-CERT-ICD) study.
Disclosures: The study received funding from the European Community’s 7th Framework Program. Dr. Bauer has no financial relationships to disclose.
Source: Bauer A et al. Lancet. 2019 Sep 2. doi: 10.1016/S0140-6736(19)31996-8.
Post-TAVR anticoagulation alone fails to cut stroke risk in AFib
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
Results of this PARTNER II substudy investigation by Kosmidou and colleagues are timely and thought provoking because they imply that some current recommendations may be insufficient for preventing stroke in patients with atrial fibrillation (AFib) undergoing transcatheter aortic valve replacement (TAVR).
Specifically, the results showed no difference in risk of stroke or the composite of death and stroke at 2 years in oral anticoagulant (OAC) and non-OAC patient groups, whereas by contrast, antiplatelet therapy was linked with reduced stroke risk versus no antithrombotic therapy, whether or not the patients received OAC.
The substudy reinforces the understanding that TAVR itself is a determinant of stroke because of mechanisms that go beyond thrombus formation in the left atrial appendage and are essentially platelet mediated.
How to manage antithrombotic therapy in patients with AFib who undergo TAVR remains a residual field of ambiguity.
However, observational studies cannot be conclusive, they said, so results of relevant prospective, randomized trials are eagerly awaited.
For example, the effects of novel oral anticoagulants versus vitamin K antagonists will be evaluated in the ENVISAGE-TAVI study, as well as the ATLANTIS trial, which will additionally include non-OAC patients.
The relative benefits of OAC alone versus OAC plus antiplatelet therapy will be evaluated in the AVATAR study, which will include AFib-TAVR patients randomized to OAC versus OAC plus aspirin, while the POPular-TAVI and CLOE trials will also include cohorts that help provide a more eloquent answer regarding the benefit-risk ratio of combining antiplatelet therapy and OAC in these patients.
Davide Capodanno, MD, PhD, and Antonio Greco, MD, of the University of Catania (Italy) made these comments in an accompanying editorial (JACC: Cardiovasc Interv. 2019 Aug 19. doi: 10.1016/j.jcin.2019.07.004). Dr. Capodanno reported disclosures related to Abbott Vascular, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi. Dr. Greco reported having no relevant disclosures.
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
In patients with atrial fibrillation (AFib) who have undergone transcatheter aortic valve replacement (TAVR) and had a CHA2DS2-VASc score of at least 2, oral anticoagulant (OAC) therapy alone was not linked to reduced stroke risk.
By contrast, antiplatelet therapy was linked to a reduced risk of stroke in those AFib-TAVR patients, regardless of whether an oral anticoagulant was on board, according to results of a substudy of the randomized PARTNER II (Placement of Aortic Transcatheter Valve II) trial and its associated registries.
“Anticoagulant therapy was associated with a reduced risk of stroke and the composite of death or stroke when used concomitantly with uninterrupted antiplatelet therapy following TAVR,” concluded authors of the analysis, led by Ioanna Kosmidou, MD, PhD, of Columbia University in New York.
Taken together, these findings suggest OAC alone is “not sufficient” to prevent cerebrovascular events after TAVR in patients with AFib, Dr. Kosmidou and colleagues reported in JACC: Cardiovascular Interventions.
The analysis of the PARTNER II substudy included a total of 1,621 patients with aortic stenosis treated with TAVR who had a history of AFib and an absolute indication for anticoagulation as evidenced by a CHA2DS2-VASc score of at least 2.
Despite the absolute indication for anticoagulation, more than 40% of these patients were not prescribed an OAC upon discharge, investigators wrote, though the rate of nonprescribing decreased over the 5-year enrollment period of 2011-2015.
OAC therapy alone was not linked to reduced stroke risk in this cohort, investigators said. After 2 years, the rate of stroke was 6.6% for AFib-TAVR patients on anticoagulant therapy, and 5.6% for those who were not on anticoagulant therapy, a nonsignificant difference at P = 0.53, according to the reported data.
By contrast, uninterrupted antiplatelet therapy reduced both risk of stroke and risk of the composite endpoint of stroke and death at 2 years “irrespective of concomitant anticoagulation,” Dr. Kosmidou and coinvestigators wrote in the report.
The stroke rates were 5.4% for antiplatelet therapy plus OAC, versus 11.1% for those receiving neither antithrombotic treatment (P = 0.03), while the rates of stroke or death were 29.7% and 40.1%, respectively (P = 0.01), according to investigators.
After adjustment, stroke risk was not significantly reduced for OAC when compared with no OAC or antiplatelet therapy (HR, 0.61; P = .16), whereas stroke risk was indeed reduced for antiplatelet therapy alone (HR, 0.32; P = .002) and antiplatelet therapy with oral anticoagulation (HR, 0.44; P = .018).
The PARTNER II study was funded by Edwards Lifesciences. Senior author Martin B. Leon, MD, and several other study coauthors reported disclosures related to Edwards Lifesciences, in addition to Abbott Vascular, Cordis, Medtronic, Boston Scientific, and other companies. Dr. Kosmidou reported no disclosures.
SOURCE: Kosmidou I et al. JACC Cardiovasc Interv. 2019;12:1580-9.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
How thin should we go?
An 88-year-old man with hypertension, chronic obstructive pulmonary disease, and atrial fibrillation presents with severe cerebral palsy and is diagnosed with a non–ST-elevation MI. He is found to have 90% left anterior descending artery occlusion and receives a drug-eluting stent. His current medications include warfarin, tiotropium, amlodipine, aspirin, and lisinopril. What anticoagulant therapy should he receive?
A) Clopidogrel, warfarin, and aspirin
B) Clopidogrel and aspirin
C) Clopidogrel and warfarin
D) Warfarin
E) Warfarin and aspirin
This issue comes up frequently with our patients with atrial fibrillation who are on anticoagulation, then have a coronary event and have a stent placed. What is the best approach to anticoagulation? I think for this patient adding clopidogrel, continuing warfarin, and stopping aspirin would be the best of the options presented.
Elderly patients have a higher risk of bleeding. They also have a greater chance of accumulating cardiovascular disease (atrial fibrillation, cardiac allograft vasculopathy, and valvular disease) that requires anticoagulation. Dewilde et al. studied the difference in bleeding risk in patients who were on oral anticoagulants who then underwent a percutaneous coronary intervention.1 Patients were assigned clopidogrel alone or clopidogrel plus aspirin in addition to their oral anticoagulant (warfarin). There was a significant increase in all-cause mortality in the patients who received clopidogrel plus aspirin (P = .027), and no significant difference in cardiac mortality between the two groups. There was a much higher risk of bleeding (44.4%) in the patients receiving triple therapy, compared with the double-therapy group (19.4%; P less than .0001).
In a large meta-analysis of over 7,000 patients by D’Ascenzo et al., there was no difference in thrombotic risk between double and triple therapy, and lower bleeding risk in patients who received double therapy.2
In a recently published article, Lopes et al. looked at the benefits and risks of antithrombotic therapy after acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation.3 The study included 4,614 patients, all of whom received a P2Y12 inhibitor. In addition, they received either apixaban or warfarin, and either aspirin or placebo. The patients who received apixaban had a lower risk of bleeding than those receiving warfarin (P less than .001), and those receiving aspirin had a higher risk than those receiving placebo (hazard ratio, 1.89; P less than .001). Patients using the combination of apixaban plus placebo had the lowest event rate per 100 years (16.8), followed by warfarin plus placebo (26.7), then apixaban plus aspirin (33.6), with warfarin plus aspirin having the highest event rate (49.1). The conclusion for the study was that regimens with apixaban without aspirin had less bleeding and hospitalizations without increased ischemic events, compared with regimens of warfarin with or without aspirin.
Pearl: Avoid using triple anticoagulant therapy by eliminating aspirin.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Dewilde WJ et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet. 2013 Mar 30;381(9872):1107-15.
2. D’Ascenzo F et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015 May 1;115(9):1185-93.
3. Lopes RD et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-24.
An 88-year-old man with hypertension, chronic obstructive pulmonary disease, and atrial fibrillation presents with severe cerebral palsy and is diagnosed with a non–ST-elevation MI. He is found to have 90% left anterior descending artery occlusion and receives a drug-eluting stent. His current medications include warfarin, tiotropium, amlodipine, aspirin, and lisinopril. What anticoagulant therapy should he receive?
A) Clopidogrel, warfarin, and aspirin
B) Clopidogrel and aspirin
C) Clopidogrel and warfarin
D) Warfarin
E) Warfarin and aspirin
This issue comes up frequently with our patients with atrial fibrillation who are on anticoagulation, then have a coronary event and have a stent placed. What is the best approach to anticoagulation? I think for this patient adding clopidogrel, continuing warfarin, and stopping aspirin would be the best of the options presented.
Elderly patients have a higher risk of bleeding. They also have a greater chance of accumulating cardiovascular disease (atrial fibrillation, cardiac allograft vasculopathy, and valvular disease) that requires anticoagulation. Dewilde et al. studied the difference in bleeding risk in patients who were on oral anticoagulants who then underwent a percutaneous coronary intervention.1 Patients were assigned clopidogrel alone or clopidogrel plus aspirin in addition to their oral anticoagulant (warfarin). There was a significant increase in all-cause mortality in the patients who received clopidogrel plus aspirin (P = .027), and no significant difference in cardiac mortality between the two groups. There was a much higher risk of bleeding (44.4%) in the patients receiving triple therapy, compared with the double-therapy group (19.4%; P less than .0001).
In a large meta-analysis of over 7,000 patients by D’Ascenzo et al., there was no difference in thrombotic risk between double and triple therapy, and lower bleeding risk in patients who received double therapy.2
In a recently published article, Lopes et al. looked at the benefits and risks of antithrombotic therapy after acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation.3 The study included 4,614 patients, all of whom received a P2Y12 inhibitor. In addition, they received either apixaban or warfarin, and either aspirin or placebo. The patients who received apixaban had a lower risk of bleeding than those receiving warfarin (P less than .001), and those receiving aspirin had a higher risk than those receiving placebo (hazard ratio, 1.89; P less than .001). Patients using the combination of apixaban plus placebo had the lowest event rate per 100 years (16.8), followed by warfarin plus placebo (26.7), then apixaban plus aspirin (33.6), with warfarin plus aspirin having the highest event rate (49.1). The conclusion for the study was that regimens with apixaban without aspirin had less bleeding and hospitalizations without increased ischemic events, compared with regimens of warfarin with or without aspirin.
Pearl: Avoid using triple anticoagulant therapy by eliminating aspirin.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Dewilde WJ et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet. 2013 Mar 30;381(9872):1107-15.
2. D’Ascenzo F et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015 May 1;115(9):1185-93.
3. Lopes RD et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-24.
An 88-year-old man with hypertension, chronic obstructive pulmonary disease, and atrial fibrillation presents with severe cerebral palsy and is diagnosed with a non–ST-elevation MI. He is found to have 90% left anterior descending artery occlusion and receives a drug-eluting stent. His current medications include warfarin, tiotropium, amlodipine, aspirin, and lisinopril. What anticoagulant therapy should he receive?
A) Clopidogrel, warfarin, and aspirin
B) Clopidogrel and aspirin
C) Clopidogrel and warfarin
D) Warfarin
E) Warfarin and aspirin
This issue comes up frequently with our patients with atrial fibrillation who are on anticoagulation, then have a coronary event and have a stent placed. What is the best approach to anticoagulation? I think for this patient adding clopidogrel, continuing warfarin, and stopping aspirin would be the best of the options presented.
Elderly patients have a higher risk of bleeding. They also have a greater chance of accumulating cardiovascular disease (atrial fibrillation, cardiac allograft vasculopathy, and valvular disease) that requires anticoagulation. Dewilde et al. studied the difference in bleeding risk in patients who were on oral anticoagulants who then underwent a percutaneous coronary intervention.1 Patients were assigned clopidogrel alone or clopidogrel plus aspirin in addition to their oral anticoagulant (warfarin). There was a significant increase in all-cause mortality in the patients who received clopidogrel plus aspirin (P = .027), and no significant difference in cardiac mortality between the two groups. There was a much higher risk of bleeding (44.4%) in the patients receiving triple therapy, compared with the double-therapy group (19.4%; P less than .0001).
In a large meta-analysis of over 7,000 patients by D’Ascenzo et al., there was no difference in thrombotic risk between double and triple therapy, and lower bleeding risk in patients who received double therapy.2
In a recently published article, Lopes et al. looked at the benefits and risks of antithrombotic therapy after acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation.3 The study included 4,614 patients, all of whom received a P2Y12 inhibitor. In addition, they received either apixaban or warfarin, and either aspirin or placebo. The patients who received apixaban had a lower risk of bleeding than those receiving warfarin (P less than .001), and those receiving aspirin had a higher risk than those receiving placebo (hazard ratio, 1.89; P less than .001). Patients using the combination of apixaban plus placebo had the lowest event rate per 100 years (16.8), followed by warfarin plus placebo (26.7), then apixaban plus aspirin (33.6), with warfarin plus aspirin having the highest event rate (49.1). The conclusion for the study was that regimens with apixaban without aspirin had less bleeding and hospitalizations without increased ischemic events, compared with regimens of warfarin with or without aspirin.
Pearl: Avoid using triple anticoagulant therapy by eliminating aspirin.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Dewilde WJ et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet. 2013 Mar 30;381(9872):1107-15.
2. D’Ascenzo F et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015 May 1;115(9):1185-93.
3. Lopes RD et al. Antithrombotic therapy after acute coronary syndrome or PCI in atrial fibrillation. N Engl J Med. 2019 Apr 18;380(16):1509-24.
AI technology meets AFib detection
An artificial intelligence-enabled ECG model identified patients with intermittent atrial fibrillation in a 10-second test with 83% accuracy, based on data from more than 180,000 individuals.
“We have previously shown convolution neural networks can evaluate the resting ECG for detection of antiarrhythmic drug levels, abnormal electrolytes levels, and detection of asymptomatic left ventricular dysfunction, providing proof of concept that clinically important phenomena can be detected with artificial intelligence (AI) applications to the ECG,” wrote Zachi I. Attia, an electrical engineer and a primary author of the study, is with the Mayo Clinic, Rochester, Minn., and colleagues.
In a study published in the Lancet, the researchers reviewed data from 649,931 normal sinus rhythm ECGs collected from 180,922 adults between December 1993 and July 2017.
The ECGs were divided into three groups: training (454,789 ECGs from 126,526 patients) internal validation (64,340 ECGs from 18,116 patients) and testing (130,802 ECGs from 36,280 patients). The primary outcome was whether the AI-programmed ECG could identify AFib in a total of 3,051 patients in the testing data set who had verified AFib before being tested with the AI device. The AI-enabled ECG was designed to detect subtle changes using neural network technology previously used by the researchers to identify ventricular dysfunction.
Overall, a single ECG scan identified AFib with an accuracy of 79.4%, an area under the curve (AUC) of 0.87, sensitivity of 79.0%, and specificity of 79.5%. When researchers reviewed multiple ECGs from a 1-month window of either the study start date or 31 days before the first AFib, the accuracy increased to 83.3%, with an AUC of 0.90, sensitivity of 82.3%, and specificity of 83.4%.
The results support the use of subtle changes on normal sinus rhythm ECG to identify patient with potentially undetected AFib, and suggest that AI-enabled ECGs could be used at the point of care to identify patients at risk after unexplained strokes, also known as embolic stroke of undetermined source (ESUS), or heart failure, the researchers noted.
“Although it would require further study, it is possible that this algorithm could identify a high-risk subset of patients with ESUS who could benefit from empirical anticoagulation,” the researchers said.
The study findings were limited by several factors, including possible mislabeling of patients with unidentified atrial fibrillation who were classified negative. In addition, the prevalence of AFib in the study population may be higher than in the general population, they said.
However, the results suggest that use a noninvasive, widely available, point of care test to identify AFib “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” they concluded.
This study was funded by internal resources of the Mayo Clinic. The researchers had no financial conflicts to disclose.
SOURCE: Attia ZI et al. Lancet. 2019 Aug 1. doi. org/10.1016/S0140-6736(19)31721-0.
This artificial intelligence-enabled ECG interpretation is groundbreaking in creating an algorithm to reveal the likelihood of atrial fibrillation in ECGs showing sinus rhythm.
AFib is now considered a global pandemic and needs to be detected not only to manage the arrhythmia but also to prevent comorbidities and death.
A 10-second, 12-lead ECG in current clinical practice is unlikely to reveal possible AFib if not present in this short monitoring time. However, the findings have clinical importance, particularly in identifying silent AFib and may have important implications for secondary prevention of patients with embolic stroke of undetermined source in terms of providing appropriate oral anticoagulation to prevent recurrences of stroke. The AI-enabled algorithm would require further validation in a different patient cohort, testing a healthier out-of-hospital population, as well as a rigorous prospective clinical trial assessment.
Future research areas include combining ECG algorithms with demographic variables, clinical features, and biomarkers, as well as exploring the use of wearable devices linking these variables and AI for smart monitoring to diagnose AFib.
Jeroen Hendriks, MD, of the University of Adelaide (Australia), and Larissa Fabritz, MD, of the University of Birmingham (England), made these comments in an accompanying editorial. Dr. Hendriks disclosed lecture or consulting fees from Medtronic and Pfizer/Bristol-Myers Squibb. Dr. Fabritz is the inventor of two patents and disclosed research grants and nonfinancial support from European research institutions and Gilead.
This artificial intelligence-enabled ECG interpretation is groundbreaking in creating an algorithm to reveal the likelihood of atrial fibrillation in ECGs showing sinus rhythm.
AFib is now considered a global pandemic and needs to be detected not only to manage the arrhythmia but also to prevent comorbidities and death.
A 10-second, 12-lead ECG in current clinical practice is unlikely to reveal possible AFib if not present in this short monitoring time. However, the findings have clinical importance, particularly in identifying silent AFib and may have important implications for secondary prevention of patients with embolic stroke of undetermined source in terms of providing appropriate oral anticoagulation to prevent recurrences of stroke. The AI-enabled algorithm would require further validation in a different patient cohort, testing a healthier out-of-hospital population, as well as a rigorous prospective clinical trial assessment.
Future research areas include combining ECG algorithms with demographic variables, clinical features, and biomarkers, as well as exploring the use of wearable devices linking these variables and AI for smart monitoring to diagnose AFib.
Jeroen Hendriks, MD, of the University of Adelaide (Australia), and Larissa Fabritz, MD, of the University of Birmingham (England), made these comments in an accompanying editorial. Dr. Hendriks disclosed lecture or consulting fees from Medtronic and Pfizer/Bristol-Myers Squibb. Dr. Fabritz is the inventor of two patents and disclosed research grants and nonfinancial support from European research institutions and Gilead.
This artificial intelligence-enabled ECG interpretation is groundbreaking in creating an algorithm to reveal the likelihood of atrial fibrillation in ECGs showing sinus rhythm.
AFib is now considered a global pandemic and needs to be detected not only to manage the arrhythmia but also to prevent comorbidities and death.
A 10-second, 12-lead ECG in current clinical practice is unlikely to reveal possible AFib if not present in this short monitoring time. However, the findings have clinical importance, particularly in identifying silent AFib and may have important implications for secondary prevention of patients with embolic stroke of undetermined source in terms of providing appropriate oral anticoagulation to prevent recurrences of stroke. The AI-enabled algorithm would require further validation in a different patient cohort, testing a healthier out-of-hospital population, as well as a rigorous prospective clinical trial assessment.
Future research areas include combining ECG algorithms with demographic variables, clinical features, and biomarkers, as well as exploring the use of wearable devices linking these variables and AI for smart monitoring to diagnose AFib.
Jeroen Hendriks, MD, of the University of Adelaide (Australia), and Larissa Fabritz, MD, of the University of Birmingham (England), made these comments in an accompanying editorial. Dr. Hendriks disclosed lecture or consulting fees from Medtronic and Pfizer/Bristol-Myers Squibb. Dr. Fabritz is the inventor of two patents and disclosed research grants and nonfinancial support from European research institutions and Gilead.
An artificial intelligence-enabled ECG model identified patients with intermittent atrial fibrillation in a 10-second test with 83% accuracy, based on data from more than 180,000 individuals.
“We have previously shown convolution neural networks can evaluate the resting ECG for detection of antiarrhythmic drug levels, abnormal electrolytes levels, and detection of asymptomatic left ventricular dysfunction, providing proof of concept that clinically important phenomena can be detected with artificial intelligence (AI) applications to the ECG,” wrote Zachi I. Attia, an electrical engineer and a primary author of the study, is with the Mayo Clinic, Rochester, Minn., and colleagues.
In a study published in the Lancet, the researchers reviewed data from 649,931 normal sinus rhythm ECGs collected from 180,922 adults between December 1993 and July 2017.
The ECGs were divided into three groups: training (454,789 ECGs from 126,526 patients) internal validation (64,340 ECGs from 18,116 patients) and testing (130,802 ECGs from 36,280 patients). The primary outcome was whether the AI-programmed ECG could identify AFib in a total of 3,051 patients in the testing data set who had verified AFib before being tested with the AI device. The AI-enabled ECG was designed to detect subtle changes using neural network technology previously used by the researchers to identify ventricular dysfunction.
Overall, a single ECG scan identified AFib with an accuracy of 79.4%, an area under the curve (AUC) of 0.87, sensitivity of 79.0%, and specificity of 79.5%. When researchers reviewed multiple ECGs from a 1-month window of either the study start date or 31 days before the first AFib, the accuracy increased to 83.3%, with an AUC of 0.90, sensitivity of 82.3%, and specificity of 83.4%.
The results support the use of subtle changes on normal sinus rhythm ECG to identify patient with potentially undetected AFib, and suggest that AI-enabled ECGs could be used at the point of care to identify patients at risk after unexplained strokes, also known as embolic stroke of undetermined source (ESUS), or heart failure, the researchers noted.
“Although it would require further study, it is possible that this algorithm could identify a high-risk subset of patients with ESUS who could benefit from empirical anticoagulation,” the researchers said.
The study findings were limited by several factors, including possible mislabeling of patients with unidentified atrial fibrillation who were classified negative. In addition, the prevalence of AFib in the study population may be higher than in the general population, they said.
However, the results suggest that use a noninvasive, widely available, point of care test to identify AFib “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” they concluded.
This study was funded by internal resources of the Mayo Clinic. The researchers had no financial conflicts to disclose.
SOURCE: Attia ZI et al. Lancet. 2019 Aug 1. doi. org/10.1016/S0140-6736(19)31721-0.
An artificial intelligence-enabled ECG model identified patients with intermittent atrial fibrillation in a 10-second test with 83% accuracy, based on data from more than 180,000 individuals.
“We have previously shown convolution neural networks can evaluate the resting ECG for detection of antiarrhythmic drug levels, abnormal electrolytes levels, and detection of asymptomatic left ventricular dysfunction, providing proof of concept that clinically important phenomena can be detected with artificial intelligence (AI) applications to the ECG,” wrote Zachi I. Attia, an electrical engineer and a primary author of the study, is with the Mayo Clinic, Rochester, Minn., and colleagues.
In a study published in the Lancet, the researchers reviewed data from 649,931 normal sinus rhythm ECGs collected from 180,922 adults between December 1993 and July 2017.
The ECGs were divided into three groups: training (454,789 ECGs from 126,526 patients) internal validation (64,340 ECGs from 18,116 patients) and testing (130,802 ECGs from 36,280 patients). The primary outcome was whether the AI-programmed ECG could identify AFib in a total of 3,051 patients in the testing data set who had verified AFib before being tested with the AI device. The AI-enabled ECG was designed to detect subtle changes using neural network technology previously used by the researchers to identify ventricular dysfunction.
Overall, a single ECG scan identified AFib with an accuracy of 79.4%, an area under the curve (AUC) of 0.87, sensitivity of 79.0%, and specificity of 79.5%. When researchers reviewed multiple ECGs from a 1-month window of either the study start date or 31 days before the first AFib, the accuracy increased to 83.3%, with an AUC of 0.90, sensitivity of 82.3%, and specificity of 83.4%.
The results support the use of subtle changes on normal sinus rhythm ECG to identify patient with potentially undetected AFib, and suggest that AI-enabled ECGs could be used at the point of care to identify patients at risk after unexplained strokes, also known as embolic stroke of undetermined source (ESUS), or heart failure, the researchers noted.
“Although it would require further study, it is possible that this algorithm could identify a high-risk subset of patients with ESUS who could benefit from empirical anticoagulation,” the researchers said.
The study findings were limited by several factors, including possible mislabeling of patients with unidentified atrial fibrillation who were classified negative. In addition, the prevalence of AFib in the study population may be higher than in the general population, they said.
However, the results suggest that use a noninvasive, widely available, point of care test to identify AFib “could have important implications for atrial fibrillation screening and for the management of patients with unexplained stroke,” they concluded.
This study was funded by internal resources of the Mayo Clinic. The researchers had no financial conflicts to disclose.
SOURCE: Attia ZI et al. Lancet. 2019 Aug 1. doi. org/10.1016/S0140-6736(19)31721-0.
FROM THE LANCET
NOACs benefit early stage chronic kidney disease patients
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
The significant reduction in risk of hemorrhagic stroke, recurrent venous thromboembolism, and VTE-related deaths in patients with early-stage chronic kidney disease given a NOAC [non–vitamin K oral anticoagulants] in a meta-analysis supports clinical application, but is there a level of renal dysfunction for which clinicians should apply greater caution in extrapolating these findings? As the evidence supporting the safety and effectiveness of NOACs in the general population increases, there is a renewed interest in defining the role of anticoagulant therapy to prevent stroke and VTE in patients with chronic kidney disease and end-stage kidney disease. This interest is driven in part by uncertainty as to the benefits vs. harms of warfarin for patients with chronic kidney disease. The data in the meta-analysis by Ha and colleagues do not support any benefits for patients with end-stage disease, but the results of two ongoing clinical trials of patients with atrial fibrillation and end-stage kidney disease may offer insights.
Until the results of these trials become available, the decision to use anticoagulant therapy in patients with end-stage kidney disease will continue to require an individualized approach that balances potential benefits and harms.
Ainslie Hildebrand, MD, of University of Alberta, Edmonton; Christine Ribic, MD, of McMaster University, Hamilton, Ont.; and Deborah Zimmerman, MD, of the University of Ottawa, made these comments in an accompanying editorial (Ann Intern Med. 2019 July 15. doi:10.7326/M19-1504). Dr. Ribic disclosed grants from Pfizer, Leo Pharma, and Astellas Pharma. Dr. Hildebrand and Dr. Zimmerman had no financial conflicts to disclose.
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
Non–vitamin K oral anticoagulants (NOACs) significantly reduced the risk of stroke or systemic embolism compared to vitamin K antagonists (VKAs) for patients in the early stages of chronic kidney disease and comorbid atrial fibrillation, based on data from a meta-analysis of roughly 34,000 patients.
Chronic kidney disease increases the risk of complications including stroke, congestive heart failure, and death in patients who also have atrial fibrillation, but most trials of anticoagulant therapy to reduce the risk of such events have excluded these patients, wrote Jeffrey T. Ha, MBBS, of the George Institute for Global Health, Newtown, Australia, and colleagues.
To assess the benefits and harms of oral anticoagulants for multiple indications in chronic kidney disease patients, the researchers conducted a meta-analysis of 45 studies including 34,082 individuals. The findings were published in the Annals of Internal Medicine. The analysis included 8 trials of end stage kidney disease patients on dialysis; the remaining trials excluded patients with creatinine clearance less than 20 mL/min or an estimated glomerular filtration rate less than 15 mL/min per 1.73 m2. The interventional agents were rivaroxaban, dabigatran, apixaban, edoxaban, betrixaban, warfarin, and acenocoumarol.
A notable finding was the significant reduction in relative risk of stroke or systemic embolism (21%), hemorrhagic stroke (52%), and intracranial hemorrhage (51%) for early-stage chronic kidney disease patients with atrial fibrillation given NOACs, compared with those given VKAs.
The evidence for the superiority of NOACs over VKAs for reducing risk of venous thromboembolism (VTE) or VTE-related death was uncertain, as was the evidence to draw any conclusions about benefits and harms of either NOACs or VKAs for patients with advanced or end-stage kidney disease.
Across all trials, NOACs appeared to reduce the relative risk of major bleeding, compared with VKAs by roughly 25%, but the difference was not statistically significant, the researchers noted.
The findings were limited by the lack of evidence for oral anticoagulant use in patients with advanced chronic or end-stage kidney disease, as well as inability to assess differences among NOACs, the researchers noted. However, the results suggest that NOACs may be recommended over VKAs for the subgroup of early-stage chronic kidney disease patients with atrial fibrillation, they said.
Several additional trials are in progress, and future trials “should include not only participants with dialysis-dependent ESKD [end-stage kidney disease] but also those with CrCl [creatinine clearance of] less than 25 mL/min,” and compare NOACs with placebo as well, they noted.
Lead author Dr. Ha is supported by a University Postgraduate Award from University of New South Wales, Sydney, but had no financial conflicts to disclose; coauthors disclosed support from various organizations as well as pharmaceutical companies including Baxter, Amgen, Eli Lilly, Boehringer Ingelheim, Vifor Pharma, Janssen, Pfizer, Bristol-Myers Squibb, and GlaxoSmithKline.
SOURCE: Ha JT et al. Ann Intern Med. 2019 July 15. doi: 10.7326/M19-0087
FROM THE ANNALS OF INTERNAL MEDICINE
Almost half of sudden cardiac deaths linked to prior silent MI
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
Almost half of individuals who died of sudden cardiac death (SCD) had a myocardial scar at autopsy, indicating a prior silent myocardial infarction (SMI), in a case-controlled study.
The research team led by Juha H. Vähätalo, MD, from the University of Oulu (Finland), compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in 5,869 people in Northern Finland who had sudden cardiac deaths during 1998-2017.
Overall, 75% of the deaths were caused by coronary artery disease (CAD), and of them, 71% had no previous diagnosis of CAD. Of these latter individuals, 42% had a myocardial scar at autopsy (detected by macroscopic and microscopic evaluation of myocardium), a finding that the authors said indicated a previous, unrecognized MI.
The analysis showed that individuals with SMI were slightly older, at 69.9 years, than were those with no SMI, at 65.5 years, and were more likely to be male (83.4% vs. 75.5%).
The group with prior SMI also died during physical activity at a greater rate than did those without (18.2% vs. 12.4%), the study authors reported in their paper published in JAMA Cardiology.
The research team obtained 438 ECGs prior to SCD; 187 in individuals with SMI and 251 in the group previously diagnosed with CAD.
Of the premortem ECGs in the individuals who had had an SCD after an SMI, 67% were abnormal, the researchers reported.
The SMI group had more frequently inverted T waves (16.6% vs. 8.4%) and pathologic Q waves (12.8% vs. 6.8%), compared with the non-SMI group. Both differences were statistically significant.
Fragmented QRS was the most common marker of a scar in the SMI group, however the authors noted that the fQRS complex was “probably a sensitive marker of myocardial scarring, but its specificity is not very high”.
Overall, having at least one of the following ECG abnormalities – fQRS, Q wave, T-wave inversion, or QRS of at least 110 msec – was more common in the SMI group (66.8%) compared with the non-SMI group (55.4%).
“Among patients in whom SCD without a prior MI is the first sign of cardiac disease, a previous ECG result is likely to be normal. ... ECGs were available only in 187 individuals with SMI, so the data are not sufficient to draw definite conclusions. Rather, they support motivation for further studies on this question,” the study authors noted.
“In the future, other, more efficient methods might be useful for diagnosing SMI, in addition to standard ECGs,” such as cardiac magnetic resonance imaging, but the cost-effectiveness “is likely to be unreasonable. Therefore, screening high-risk populations with ECG to identify individuals for further examinations would probably be reasonable,” they wrote.
The research team noted some limitations of the study such as the autopsy data not revealing the size of the scar detected in the myocardium and not all individuals had an ECG recorded prior to death.
SOURCE: JAMA Cardiol. 2019 Jul 10; doi: 10.1001/jamacardio.2019.2210
FROM JAMA CARDIOLOGY
Risk of atrial fibrillation 900% higher with cancer
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
MELBOURNE – The overall prevalence of atrial fibrillation in people who have or have had cancer is 10 times that of individuals without cancer, according to a study presented at the International Society on Thrombosis and Haemostasis congress.
Cihan Ay, MD, of the division of hematology and hemostaseology at the Medical University of Vienna reported on a nationwide cohort study using health insurance data from more than 8.3 million people in Austria, including roughly 159,000 with a diagnosis of cancer and 113,000 with a diagnosis of atrial fibrillation.
The analysis found that, in individuals whose records showed a diagnosis of cancer, there was a 950% higher relative risk of also having a diagnosis of atrial fibrillation, compared with those with no cancer diagnosis.
The overall prevalence of atrial fibrillation among individuals with a cancer diagnosis was 9.8%, compared with 1.2% in those without cancer.
There was significant variation in relative risk according to age. Although the prevalence of atrial fibrillation increased with age, the highest relative risks were seen in the youngest age groups.
In those aged 12 years or under with a cancer diagnosis, the relative risk of atrial fibrillation was 150 times greater than in those without cancer, and in those aged 13-18 years, it was 200 times higher. At the other end of the age spectrum, individuals aged 70-79 years with a recorded cancer diagnosis, the relative risk of atrial fibrillation was still 130% higher than the noncancer population, and in those aged 80-90 years it was a significant 54% higher.
However, the analysis did not find any effect of gender on the risk of atrial fibrillation associated with cancer, regardless of the age group.
Researchers also examined the influence of different cancer types. They found the highest relative risk of atrial fibrillation was in persons with hematologic malignancies – at nine times the risk in the noncancer population – and the lowest was in the endocrine cancer patients, who had three times the risk.
Dr. Ay told the conference that the association between cancer and atrial fibrillation had been suggested in the literature, but it was still an unexplored field. “The exact magnitude of this association between cancer and atrial fibrillation is still unclear.”
There was also the question of what mechanisms might underlie the association. Dr. Ay pointed out that the health insurance database did not allow researchers to explore the temporal relationship between the two diagnoses, and therefore could not tell which came first.
One audience member queried whether the fact that cancer patients were likely to be visiting a clinician more frequently might mean that the atrial fibrillation would be more likely to be diagnosed.
To that, Dr. Ay suggested the significantly higher relative risk in children was supportive of the notion that cancer itself, or treatment effects, were influencing atrial fibrillation risk.
“There is evidence suggesting that cancer treatments are triggering atrial fibrillation,” he said in an interview. “Also, patients with cancer have situations of in which they are sick – they have neutropenia or sepsis and so on – which can also trigger atrial fibrillation.”
Given the limitations of the retrospective cohort study, Dr. Ay said he was hoping to do a prospective study that would enable baseline measurements of cancer patients to determine how much of the atrial fibrillation was preexisting.
“We have also more and more cancer survivors, and over the years they’re living longer and the likelihood of getting atrial fibrillation increases,” he added.
Commenting on the data, Gerald Soff, MD, chief of hematology at the Memorial Sloan Kettering Cancer Center in New York, said it was very important to quantify the association between cancer and atrial fibrillation.
“What’s striking to me is how many people with cancer come in with preexisting atrial fibrillation,” he said. “It could be that they have cancer and they’re already messed up, but we have, on a given day, several people coming in with newly diagnosed cancers, already on warfarin or apixaban or rivaroxaban because they have atrial fibrillation.”
Dr. Ay reported advisory board positions and speaking engagements for the pharmaceutical sector.
REPORTING FROM 2019 ISTH CONGRESS
Pivotal trial shows HFrEF benefits from baroreceptor stimulation
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
The results that Dr. Zile reported are obviously very promising. It was a huge step forward when researchers identified medical treatments that can safely manipulate the autonomic nervous system in patients with heart failure with reduced ejection fraction. Now we are asking what else we can do because we have run into limits on what we can accomplish with drugs alone. The BeAT-HF study is a step in that direction.
Andrew D. Krahn, MD, is professor of medicine and head of cardiology at the University of British Columbia and St. Paul’s Hospital in Vancouver. He has been a consultant to Medtronic and he has received research funding from Boston Scientific and Medtronic. He made these comments as a discussant for BeAT-HF.
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
SAN FRANCISCO – Baroreflex activation therapy met all four of its primary endpoints in its U.S. pivotal trial of 264 patients with advanced heart failure with reduced ejection fraction who were ineligible for cardiac resynchronization therapy.
The results showed that ongoing baroreflex activation therapy (BAT) via a single, stimulating electrode surgically placed on a patient’s carotid artery led to statistically significant and clinically meaningful improvements in quality of life and functional capacity while also reducing the level of a biomarker of heart failure severity in patients already on guideline-directed medical therapy, Michael R. Zile, MD, said at the annual scientific sessions of the Heart Rhythm Society. He estimated that the device is appropriate for perhaps a third or more of patients with heart failure with reduced ejection fraction (HFrEF), specifically patients with New York Heart Association functional class III disease who are not candidates for treatment with cardiac resynchronization therapy (CRT) and with a blood level of N-terminal pro–brain natriuretic peptide (NT-proBNP) of less than 1,600 pg/mL, a cutoff that excludes patients with very severe class III HFrEF and focuses on those who benefited in the study.
“To our knowledge, this is the first successful pivotal trial of device-based neuromodulation therapy in HFrEF patients,” said Dr. Zile, professor of medicine at the Medical University of South Carolina in Charleston. “We think that BAT fills an unmet need” in a large number of HFrEF patients. He stressed that the placement of the single, 2-mm, unilateral electrode on the baroreceptor-containing carotid sinus is an “extremely safe and simple” surgery. The electrode attaches to a small, subcutaneously placed generator.
Dr. Zile attributed the treatment’s success, in contrast to a prior, failed attempt to treat HFrEF by vagus nerve stimulation (J Am Coll Cardiol. 2016 Jul 12;68[2]:147-56) to BAT’s action via the patient’s brain, which processes the afferent signal it receives from stimulation to in turn inhibit sympathetic activation and upregulate parasympathetic innervation, with both actions benefiting HFrEF patients. “The integrated autonomic balance is the real difference with this device,” he said. Other helpful effects from BAT are reduced heart rate, reduced cardiac remodeling, increased vasodilation, a decrease in elevated blood pressure, increased diuresis, and a drop in renin secretion. The pivotal trial built on findings from a phase 2 study (JACC Heart Fail. 2015 Jun;3[6]:487-96).
The BeAT-HF (Barostim Neo - Baroreflex Activation Therapy for Heart Failure) trial enrolled patients with class III HFrEF with a left ventricular ejection fraction of 35% or less and a 6-minute walk distance of 150-400 m, who were ineligible for CRT, on optimal medical therapy, and who had an elevated NT-proBNP level. After the study randomized 271 patients to either BAT or ongoing medical therapy only (without use of a sham procedure or sham BAT), the results showed a statistically significant benefit for three of the four primary endpoints. Patients treated with BAT for 6 months had statistically significant and clinically meaningful improvements in their quality of life scores as measured on the Minnesota Living With Heart Failure Questionnaire, in their function as measured by the 6-min walk distance, and in the treatment’s safety, based on the combined rate of major adverse neurological and cardiovascular events, which occurred in 6% of patients treated with BAT, which was significantly better than the study’s prespecified performance goal of 15%.
However, for the fourth primary endpoint – reduction in blood levels of NT-proBNP – the BAT-treated patients showed no significant improvement, compared with the controls. The design of BeAT-HF called for consultation with the Food and Drug Administration in such a situation, and further data analysis showed that the problem may have been that some enrolled patients entered with extremely elevated levels of this biomarker. The agency authorized an added protocol that randomized 102 additional patients that matched the initial cohort but had a requirement for an NT-proBNP level of less than 1,600 pg/mL. The 6-month outcomes of these patients were combined with the previously determined outcomes for 162 of the original 271 patients who entered with NT-proBNP levels within the specified limit, producing a total, final study group of 264 patients, of whom 120 received BAT and completed 6-month follow-up, and 125 received medical therapy only and had 6-month follow-up. These patients averaged about 63 years of age, and 20% were women. On average they were on four heart failure medications, and more than three-quarters also had an implanted cardiac device.
The results from an analysis of this cohort showed a statistically significant, 25% relative reduction in blood levels of NT-proBNP in the BAT patients, compared with the controls, and it also confirmed statistically significant and meaningful improvements in quality of life and function on BAT, compared with controls. The 14-point average improvement in the quality of life score in BAT patients, compared with the controls, on the Minnesota Living With Heart Failure Questionnaire was nearly triple the point improvement that’s considered clinically meaningful and hence was “very convincing” about the treatment’s efficacy, noted Dr. Zile, who is also director of cardiology at the VA Medical Center in Charleston. The 25% drop in average NT-proBNP levels “predicts a marked reduction in morbidity and mortality.” He added that researchers have developed a percutaneous, transcatheter method for placing the carotid electrode that will soon undergo clinical testing.
These results “reconfirm the safety of BAT,” but are limited by a relatively short follow-up of 6 months, no data on survival benefit, and by not having echocardiographic data on possible cardiac remodeling, commented Sanjeev Saksena, MD, medical director of the Electrophysiology Research Foundation in Warren, N.J.
BeAT-HF was sponsored by CVRx, the company developing the baroreflex activation device. Dr. Zile has been a consultant to CVRx and to Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck, and Novartis. Dr. Saksena had no disclosures.
SOURCE: Zile MR. Heart Rhythm 2019, Abstract, S-LBCT01-04.
REPORTING FROM HEART RHYTHM 2019
DOACs surpass warfarin in low-weight AFib patients
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
SAN FRANCISCO – The direct-acting anticoagulants, as a class, were more effective and at least as safe as warfarin in low-weight and very-low-weight patients with atrial fibrillation in an adjusted analysis of real-world outcomes data from more than 21,000 Korean patients.
The analysis also showed that the direct-acting oral anticoagulants (DOACs) had the best safety and efficacy on low-weight patients when used at the labeled dosages, with blunted efficacy and safety at dosages that either exceeded or fell short of labeled levels, So-Ryoung Lee, MD, said at the annual scientific sessions of the Heart Rhythm Society.
The overall superiority of DOACs by both efficacy and safety also generally extended to the subgroup of very-low-weight patients, those with weights of less than 50 kg. In this subgroup, which was 28% of the total population studied, the composite adverse event outcome occurred 33% less often among patients treated with a DOAC relative to patients treated with warfarin, a statistically significant difference, said Dr. Lee, a cardiologist at Seoul (South Korea) National University Hospital. Among all patients with weights of 60 kg (132 pounds) or less, the composite outcome occurred 34% less often in the DOAC-treated patients relative to the warfarin-treated patients, also a statistically significant difference.
Dr. Lee and colleagues used a Korean National Health Insurance database that included information on more than 600,000 adults with atrial fibrillation (AFib) as of January 2013. The researchers whittled this down to 21,678 patients who began for the first time treatment with an oral anticoagulant starting during or after January 2014; had no history of a stroke, intracranial hemorrhage, or gastrointestinal bleed; and weighed no more than 60 kg. This cohort included 7,575 (35%) who received warfarin treatment, and 14,103 (65%) who received a DOAC. Within the DOAC-treated group, 42% received rivaroxaban (Xarelto), 26% dabigatran (Pradaxa), 24% apixaban (Eliquis), and 8% edoxaban (Savaysa).
To account for baseline differences in demographics and comorbidities between the patients treated with a DOAC and those who received warfarin, Dr. Lee and her associates did propensity score adjustment, which resulted in similar cohorts of 6,692 patients treated with warfarin and 12,810 patients treated with a DOAC. The average age of these patients was 73 years, a third were men, and the average body mass index was just over 22 kg/m2.
The events that the researchers tallied during follow-up through December 2016 included rates of all-cause death, ischemic stroke, intracranial hemorrhage, hospitalization for GI bleeding, hospitalization for major bleeding, and the composite of these five outcomes.
In the propensity-score adjusted full cohort of all patients who weighed 60 kg or less, the rate of each of these five outcomes, as well as the composite outcome, occurred statistically significantly less often among the DOAC-treated patients than in those on warfarin. The reductions ranged from a 41% lower incidence of ischemic stroke on DOAC treatment compared with warfarin treatment, to an 18% reduced rate of hospitalization for a GI bleed, compared with warfarin-treated patients. In the subgroup of patients who weighed less than 50 kg (110 pounds), the reductions ranged from a 41% cut in ischemic stroke on a DOAC compared with warfarin to a 24% relative reduction in the rate of hospitalization for a major bleed, a difference that just reached statistical significance. The outcome of hospitalization for a GI bleed showed no significant between-group difference among very-low-weight patients, but the rates of intracranial hemorrhage and all-cause death also showed statistically significant lower rates among DOAC-treated patients.
Nearly two-thirds of the patients on a DOAC received the label-appropriate dose of the drug, but 31% received a dosage that was below the labeled level while 4% received a dosage above the labeled level. An analysis that divided the NOAC patients by the appropriateness of their treatment dosages showed that patients on the correct dosages fared best. For example, in the total cohort of patients who weighed 60 kg or less, those on the correct DOAC dosage had a 9.1% rate of the combined endpoint. Patients on a low DOAC dosage did about as well as did the patients on warfarin, with a combined event rate of 11.6% in each of these subgroups. The worst outcomes occurred among the small number of patients on an inappropriately-high DOAC dosage, with a combined event rate of 15.4%. The researchers found a similar pattern among patients who weighed less than 50 kg.
Dr. Lee had no disclosures.
SOURCE: Lee SR et al. HRS 2019, Abstract S-AB30-05.
REPORTING FROM HEART RHYTHM 2019