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AF risk is elevated after early-stage breast cancer diagnosis
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.
“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”
The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.
An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.
Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.
At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.
Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).
Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.
“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.
“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.
Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.
SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.
FROM JAMA NETWORK OPEN
Dual therapy best for AFib with ACS no matter the treatment strategy
SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.
The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.
“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.
In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.
At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).
Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).
Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.
“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”
Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”
Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”
The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.
SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.
SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.
The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.
“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.
In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.
At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).
Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).
Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.
“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”
Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”
Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”
The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.
SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.
SAN FRANCISCO – Anticoagulation with apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have an acute coronary syndrome, compared with regimens that include vitamin K antagonists, aspirin, or both.
The findings come from a prespecified analysis of data from the AUGUSTUS trial presented by Stephan Windecker, MD, at the Transcatheter Cardiovascular Therapeutics annual meeting.
“This study adds very important information [to the notion] that triple therapy in the setting of atrial fibrillation and PCI [percutaneous coronary intervention] is really not the way to go,” Ori Ben-Yehuda, MD, FACC, executive director of the Cardiovascular Research Foundation’s Clinical Trials Center, said during a media briefing.
In the recent multicenter AUGUSTUS trial, Dr. Windecker, of the department of cardiology at Bern University Hospital, Switzerland, and colleagues found that among 4,614 patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, apixaban without aspirin resulted in less bleeding, fewer hospitalizations, and no significant differences in ischemic events compared with regimens that included a vitamin K antagonist (VKA), aspirin, or both (N Engl J Med. 2019;380:1509-24). For this prespecified analysis, the researchers used a 2×2 factorial design to compare apixaban with VKA and aspirin with placebo in the AUGUSTUS trial participants with ACS treated medically (group 1; 1,097 patients, or 24%), those with ACS treated with PCI (group 2; 1,714 patients, or 37%), and those undergoing elective PCI (group 3; 1,784 patients, or 39%). The outcomes of interest were bleeding, death, and hospitalization as well as death and ischemic events by antithrombotic strategy in the study participants. This marks the only trial in the field that included patients with ACS managed medically, Dr. Windecker said.
At baseline, the median age of patients was 71 years, 30% were female, 36% had diabetes, and 45% had heart failure. Patients managed medically were younger (a median age of 70) and more frequently female; 57% presented with heart failure. The groups had identical CHA2DS2VASc scores (4), and very similar HAS-BLED scores (2 in groups 1 and 2, and 3 in group 3).
Apixaban compared with VKA showed lower International Society on Thrombosis and Haemostasis–defined major or clinically relevant nonmajor bleeding among patients in group 1 (HR, 0.44), group 2 (HR, 0.68), and group 3 (HR, 0.82) (P for interaction = .052). Apixaban compared with VKA reduced death or hospitalization among patients in group 1 (HR, 0.71), group 2 (HR 0.88), and group 3 (HR, 0.87) (P for interaction = .345). Compared with VKA, apixaban resulted in a similar effect on death and ischemic events among patients in all three treatment groups (P for interaction = .356).
Compared with placebo, aspirin had a higher rate of bleeding among patients in group 1 (HR, 1.49), group 2 (HR, 2.02) and group 3 (HR, 1.91) (P for interaction = .479). For the same comparison, there was no difference in outcomes among the three groups for the composite of death or hospitalization and death and ischemic events.
“The overall results of the AUGUSTUS trial are consistent across the three clinically important subgroups,” Dr. Windecker said. The reasons why patients received medical therapy remain unclear, “because it was at the physician’s discretion as to whether they were treated medically or underwent PCI,” he said. “The proportion very much reflects our clinical practice, where 20%-25% of patients are treated medically. What was surprising for me is that I would have anticipated there would be more elderly patients with comorbidities, but I did anticipate that there would be more female patients (in this subgroup).”
Robert A. Harrington, MD, an interventional cardiologist at Stanford (Calif.) University who served on the Data Safety and Monitoring Board for the trial, noted that the patients with atrial fibrillation represent 7%-10% of all ACS patients, “so it’s a big population,” he said. “What’s been disappointing is that none of the trials have been big enough to uncouple the bleeding vs. ischemic issue. We don’t know the answer for how long do you need the triple therapy versus when you can switch to the double therapy.”
Dr. Windecker said that the optimal duration of short-term aspirin remains unclear in this patient population. “Whether there is a benefit of giving aspirin for 2 weeks or 4 weeks remains unanswered,” he said. “Triple therapy is not the way to go, but we need to fine-tune, and probably individualize, which patients may benefit from a certain duration of aspirin.”
The study results were published online at the time of presentation (Circulation 2019 Sep 26. doi: 10.1161/CIRCULATIONAHA.119.043308.
AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer Inc. Dr. Windecker reported having received institutional research and educational grants to Bern University Hospital from Abbott, Amgen, Bayer, BMS, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. His coauthors reported having numerous financial ties to the pharmaceutical and device industries.
SOURCE: Windecker S. TCT 2019, Late-Breaking Trials 1 session.
AT TCT 2019
Rivaroxaban bests combo therapy in post-PCI AFib
PARIS – Rivaroxaban monotherapy bested combination therapy with rivaroxaban and an antiplatelet agent for patients with atrial fibrillation and stable coronary artery disease, with significantly more deaths and bleeding events seen with combination therapy.
The pronounced imbalance in all-cause and cardiovascular mortality (the hazard ratio favoring rivaroxaban monotherapy was 9.72) came as a surprise, and led to early cessation of the multisite Japanese trial, lead investigator Satoshi Yasuda, MD, said at the annual congress of the European Society of Cardiology.
Several previous clinical trials had studied a reduced antithrombotic regimen for patients with atrial fibrillation (AFib) after percutaneous coronary intervention (PCI), said Dr. Yasuda, professor of medicine at Tohoku University, Sendai, Japan. Current guidelines recommend triple therapy with an oral anticoagulant plus aspirin and a P2Y12 inhibitor for the shortest duration possible, with combination therapy of an anticoagulant plus a P2Y12 inhibitor for up to 12 months. Once the 1-year post-PCI mark is reached, current European and American guidelines or consensus documents recommend monotherapy with an oral anticoagulant if AFib persists and the patient has stable coronary artery disease (CAD), explained Dr. Yasuda. “However, this approach has yet to be supported by evidence from randomized, controlled trials,” he said, adding “substantial numbers of patients in this situation continue to be treated with combination therapy, which indicates a gap between guidelines and clinical practice.”
The Atrial Fibrillation and Ischemic events with Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE), he said, was designed to address this practice gap, randomizing 2,200 individuals to receive monotherapy with rivaroxaban or combination therapy. A total of 1,973 patients completed follow-up.
Patients were included in the randomized, open-label, parallel-group trial if they had AFib and stable CAD and were more than 1 year out from revascularization, or if they had angiographically confirmed CAD that did not need revascularization. All 294 AFIRE study sites were in Japan.
The study’s primary endpoint for efficacy was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and all-cause death.
Most of the patients (79%) were male, and the mean age was 74 years. About 70% of patients in each treatment arm had received prior PCI, and 11% had undergone previous coronary artery bypass grafting (CABG).
The monotherapy arm received rivaroxaban 10 or 15 mg once daily depending on renal status. Patients in the combination therapy arm received rivaroxaban, plus a single antiplatelet drug. This could be 81 or 100 mg aspirin daily, clopidogrel at 50 or 75 mg/day, or prasugrel at 2.5 or 3.5 mg/day.
On the recommendation of the data and safety monitoring committee, the trial was terminated about 3 months early because significantly more all-cause deaths were being seen in the combination therapy group, said Dr. Yasuda. In the end, patients were treated under the study protocol for a median 23 months and followed up for a median 24.1 months.
Kaplan-Meier estimates for the first occurrence of the composite efficacy endpoint showed that monotherapy had a rate of 4.14% per patient-year, while combination therapy had a rate of occurrence for the efficacy endpoint of 5.75% per patient-year.
These figures yielded a statistically significant hazard ratio (HR) of 9.72 favoring monotherapy (P less than .001) for the prespecified noninferiority endpoint. In a post hoc analysis, rivaroxaban monotherapy achieved superiority over dual therapy (P = .02).
Breaking down the composite efficacy endpoint into its constituents, deaths by any cause and cardiovascular deaths primarily drove the difference in treatment arms. Seventy-three patients in the combo therapy arm and 41 in the rivaroxaban arm died of any cause, and the cause of death was cardiovascular for 43 combination therapy patients and 26 monotherapy patients. This yielded HRs favoring rivaroxaban of 0.55 for all-cause mortality and 0.59 for cardiovascular deaths.
Hazard ratios for individual cardiovascular events were not statistically significantly different between treatment arms, except for hemorrhagic stroke, which was seen in 13 patients receiving dual therapy and 4 receiving rivaroxaban alone, for a hazard ratio of 0.30.
Rivaroxaban monotherapy also bested dual therapy in safety: The HR was 0.59 for the incidence of a major bleed on rivaroxaban versus combination therapy, using International Society on Thrombosis and Haemostasis–established criteria for major bleeding. In the dual therapy arm, 58 individuals experienced major bleeding – the study’s primary safety endpoint – compared with 35 in the monotherapy arm, for a hazard ratio of 0.59; nonmajor bleeding occurred in 198 dual therapy patients and 121 monotherapy patients, yielding a hazard ratio of 0.58.
The Kaplan-Meier estimate for major bleeding on monotherapy was 1.62% per patient-year, compared with 2.76% per patient-year for those on combination therapy. These findings, said Dr. Yasuda, were “generally” consistent across prespecified subgroups that included participant stratification by age, sex, and bleeding risk, among others.
Dr. Yasuda acknowledged the many limitations of the trial. First, early termination introduced the possibility of overestimating the benefit of rivaroxaban monotherapy. Indeed, said Dr. Yasuda, “the reductions in rate of ischemic events and death from any cause with rivaroxaban monotherapy were unanticipated and are difficult to explain.”
Furthermore, the open-label trial design could be a source of bias and the use of both aspirin and P2Y12 inhibitors for antiplatelet therapy “makes it uncertain whether the benefit of rivaroxaban monotherapy applies equally to the two combination regimens,” said Dr. Yasuda.
Rivaroxaban dosing in AFIRE was tailored to the Japanese study population, noted Dr. Yasuda. This means that the study is not immediately generalizable to non-Asian populations, needing replication before fully closing the knowledge gap about best long-term management of patients with AFib and stable CAD in the United States and Western Europe.
However, Dr. Yasuda pointed out, serum rivaroxaban levels in Japanese patients taking the 10- or 15-mg dose are generally similar to those seen in white patients taking a 20-mg rivaroxaban dose.
Freek Verheugt, MD, of Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, was the discussant for the presentation. He raised an additional concern: “East Asian patients are poor metabolizers of clopidogrel, which may have resulted also in underestimation of bleeding.” He cautioned that the AFIRE results may not be applicable to patients on a novel anticoagulant other than clopidogrel, or on vitamin K antagonists.
In his detailed critique of the AFIRE results, Dr. Verheugt cited the OAC ALONE trial, which used a similar study design and was also conducted in Japan. For OAC ALONE, Dr. Verheugt pointed out that “You can see ... that it was not harmful in this 700-patient study to stop aspirin therapy 1 year after an intervention.” However, he said, “the net clinical benefit is not very different, either” between treatment arms in the OAC ALONE trial. “Given the low number of patients and the low number of events, this trial was not conclusive whatsoever” he added, so AFIRE’s findings were needed.
The safety data from AFIRE, with a study population triple that of OAC ALONE, makes the safety argument for monotherapy “a very easy winner,” said Dr. Verheugt.
Dr. Verheugt was not mystified by the lower all-cause and cardiovascular death rate in the monotherapy group. “What are the mechanisms that if you stop antiplatelet therapy you have a better ischemic outcome? How come?” asked Dr. Verheugt.
“Very likely, it is the bleeding ... that you prevent if you stop antiplatelet therapy,” he said, adding that it’s known from previous studies in individuals with acute coronary syndromes and AFib that “bleeding is correlated with mortality, and that’s also proven here.”
Though Dr. Verheugt joined Dr. Yasuda in calling for replication of the results in a non-Asian population, he concurred that the AFIRE results validate current practice for anticoagulation in AFib with stable CAD. “Stopping at 1 year is safer than continuation and, most of all, it saves lives,” he said.
Full results of AFIRE were published online at the time of Dr. Yasuda’s presentation (N Engl J Med. 2019 Sep 2. doi: 10.1056/NEJMoa1904143).
The study was funded by the Japanese Cardiovascular Research Foundation. Dr. Yasuda reported financial relationships with Abbott, Bristol-Myers, Daiichi-Sankyo, and Takeda. Dr. Verheugt reported financial relationships with BayerHealthcare, BMS/Pfizer, Boehringer-Ingelheim, and Daiichi-Sankyo.
SOURCE: Yasuda S. et al. ESC 2019, Hot Line Session 3, Abstract 3175.
PARIS – Rivaroxaban monotherapy bested combination therapy with rivaroxaban and an antiplatelet agent for patients with atrial fibrillation and stable coronary artery disease, with significantly more deaths and bleeding events seen with combination therapy.
The pronounced imbalance in all-cause and cardiovascular mortality (the hazard ratio favoring rivaroxaban monotherapy was 9.72) came as a surprise, and led to early cessation of the multisite Japanese trial, lead investigator Satoshi Yasuda, MD, said at the annual congress of the European Society of Cardiology.
Several previous clinical trials had studied a reduced antithrombotic regimen for patients with atrial fibrillation (AFib) after percutaneous coronary intervention (PCI), said Dr. Yasuda, professor of medicine at Tohoku University, Sendai, Japan. Current guidelines recommend triple therapy with an oral anticoagulant plus aspirin and a P2Y12 inhibitor for the shortest duration possible, with combination therapy of an anticoagulant plus a P2Y12 inhibitor for up to 12 months. Once the 1-year post-PCI mark is reached, current European and American guidelines or consensus documents recommend monotherapy with an oral anticoagulant if AFib persists and the patient has stable coronary artery disease (CAD), explained Dr. Yasuda. “However, this approach has yet to be supported by evidence from randomized, controlled trials,” he said, adding “substantial numbers of patients in this situation continue to be treated with combination therapy, which indicates a gap between guidelines and clinical practice.”
The Atrial Fibrillation and Ischemic events with Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE), he said, was designed to address this practice gap, randomizing 2,200 individuals to receive monotherapy with rivaroxaban or combination therapy. A total of 1,973 patients completed follow-up.
Patients were included in the randomized, open-label, parallel-group trial if they had AFib and stable CAD and were more than 1 year out from revascularization, or if they had angiographically confirmed CAD that did not need revascularization. All 294 AFIRE study sites were in Japan.
The study’s primary endpoint for efficacy was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and all-cause death.
Most of the patients (79%) were male, and the mean age was 74 years. About 70% of patients in each treatment arm had received prior PCI, and 11% had undergone previous coronary artery bypass grafting (CABG).
The monotherapy arm received rivaroxaban 10 or 15 mg once daily depending on renal status. Patients in the combination therapy arm received rivaroxaban, plus a single antiplatelet drug. This could be 81 or 100 mg aspirin daily, clopidogrel at 50 or 75 mg/day, or prasugrel at 2.5 or 3.5 mg/day.
On the recommendation of the data and safety monitoring committee, the trial was terminated about 3 months early because significantly more all-cause deaths were being seen in the combination therapy group, said Dr. Yasuda. In the end, patients were treated under the study protocol for a median 23 months and followed up for a median 24.1 months.
Kaplan-Meier estimates for the first occurrence of the composite efficacy endpoint showed that monotherapy had a rate of 4.14% per patient-year, while combination therapy had a rate of occurrence for the efficacy endpoint of 5.75% per patient-year.
These figures yielded a statistically significant hazard ratio (HR) of 9.72 favoring monotherapy (P less than .001) for the prespecified noninferiority endpoint. In a post hoc analysis, rivaroxaban monotherapy achieved superiority over dual therapy (P = .02).
Breaking down the composite efficacy endpoint into its constituents, deaths by any cause and cardiovascular deaths primarily drove the difference in treatment arms. Seventy-three patients in the combo therapy arm and 41 in the rivaroxaban arm died of any cause, and the cause of death was cardiovascular for 43 combination therapy patients and 26 monotherapy patients. This yielded HRs favoring rivaroxaban of 0.55 for all-cause mortality and 0.59 for cardiovascular deaths.
Hazard ratios for individual cardiovascular events were not statistically significantly different between treatment arms, except for hemorrhagic stroke, which was seen in 13 patients receiving dual therapy and 4 receiving rivaroxaban alone, for a hazard ratio of 0.30.
Rivaroxaban monotherapy also bested dual therapy in safety: The HR was 0.59 for the incidence of a major bleed on rivaroxaban versus combination therapy, using International Society on Thrombosis and Haemostasis–established criteria for major bleeding. In the dual therapy arm, 58 individuals experienced major bleeding – the study’s primary safety endpoint – compared with 35 in the monotherapy arm, for a hazard ratio of 0.59; nonmajor bleeding occurred in 198 dual therapy patients and 121 monotherapy patients, yielding a hazard ratio of 0.58.
The Kaplan-Meier estimate for major bleeding on monotherapy was 1.62% per patient-year, compared with 2.76% per patient-year for those on combination therapy. These findings, said Dr. Yasuda, were “generally” consistent across prespecified subgroups that included participant stratification by age, sex, and bleeding risk, among others.
Dr. Yasuda acknowledged the many limitations of the trial. First, early termination introduced the possibility of overestimating the benefit of rivaroxaban monotherapy. Indeed, said Dr. Yasuda, “the reductions in rate of ischemic events and death from any cause with rivaroxaban monotherapy were unanticipated and are difficult to explain.”
Furthermore, the open-label trial design could be a source of bias and the use of both aspirin and P2Y12 inhibitors for antiplatelet therapy “makes it uncertain whether the benefit of rivaroxaban monotherapy applies equally to the two combination regimens,” said Dr. Yasuda.
Rivaroxaban dosing in AFIRE was tailored to the Japanese study population, noted Dr. Yasuda. This means that the study is not immediately generalizable to non-Asian populations, needing replication before fully closing the knowledge gap about best long-term management of patients with AFib and stable CAD in the United States and Western Europe.
However, Dr. Yasuda pointed out, serum rivaroxaban levels in Japanese patients taking the 10- or 15-mg dose are generally similar to those seen in white patients taking a 20-mg rivaroxaban dose.
Freek Verheugt, MD, of Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, was the discussant for the presentation. He raised an additional concern: “East Asian patients are poor metabolizers of clopidogrel, which may have resulted also in underestimation of bleeding.” He cautioned that the AFIRE results may not be applicable to patients on a novel anticoagulant other than clopidogrel, or on vitamin K antagonists.
In his detailed critique of the AFIRE results, Dr. Verheugt cited the OAC ALONE trial, which used a similar study design and was also conducted in Japan. For OAC ALONE, Dr. Verheugt pointed out that “You can see ... that it was not harmful in this 700-patient study to stop aspirin therapy 1 year after an intervention.” However, he said, “the net clinical benefit is not very different, either” between treatment arms in the OAC ALONE trial. “Given the low number of patients and the low number of events, this trial was not conclusive whatsoever” he added, so AFIRE’s findings were needed.
The safety data from AFIRE, with a study population triple that of OAC ALONE, makes the safety argument for monotherapy “a very easy winner,” said Dr. Verheugt.
Dr. Verheugt was not mystified by the lower all-cause and cardiovascular death rate in the monotherapy group. “What are the mechanisms that if you stop antiplatelet therapy you have a better ischemic outcome? How come?” asked Dr. Verheugt.
“Very likely, it is the bleeding ... that you prevent if you stop antiplatelet therapy,” he said, adding that it’s known from previous studies in individuals with acute coronary syndromes and AFib that “bleeding is correlated with mortality, and that’s also proven here.”
Though Dr. Verheugt joined Dr. Yasuda in calling for replication of the results in a non-Asian population, he concurred that the AFIRE results validate current practice for anticoagulation in AFib with stable CAD. “Stopping at 1 year is safer than continuation and, most of all, it saves lives,” he said.
Full results of AFIRE were published online at the time of Dr. Yasuda’s presentation (N Engl J Med. 2019 Sep 2. doi: 10.1056/NEJMoa1904143).
The study was funded by the Japanese Cardiovascular Research Foundation. Dr. Yasuda reported financial relationships with Abbott, Bristol-Myers, Daiichi-Sankyo, and Takeda. Dr. Verheugt reported financial relationships with BayerHealthcare, BMS/Pfizer, Boehringer-Ingelheim, and Daiichi-Sankyo.
SOURCE: Yasuda S. et al. ESC 2019, Hot Line Session 3, Abstract 3175.
PARIS – Rivaroxaban monotherapy bested combination therapy with rivaroxaban and an antiplatelet agent for patients with atrial fibrillation and stable coronary artery disease, with significantly more deaths and bleeding events seen with combination therapy.
The pronounced imbalance in all-cause and cardiovascular mortality (the hazard ratio favoring rivaroxaban monotherapy was 9.72) came as a surprise, and led to early cessation of the multisite Japanese trial, lead investigator Satoshi Yasuda, MD, said at the annual congress of the European Society of Cardiology.
Several previous clinical trials had studied a reduced antithrombotic regimen for patients with atrial fibrillation (AFib) after percutaneous coronary intervention (PCI), said Dr. Yasuda, professor of medicine at Tohoku University, Sendai, Japan. Current guidelines recommend triple therapy with an oral anticoagulant plus aspirin and a P2Y12 inhibitor for the shortest duration possible, with combination therapy of an anticoagulant plus a P2Y12 inhibitor for up to 12 months. Once the 1-year post-PCI mark is reached, current European and American guidelines or consensus documents recommend monotherapy with an oral anticoagulant if AFib persists and the patient has stable coronary artery disease (CAD), explained Dr. Yasuda. “However, this approach has yet to be supported by evidence from randomized, controlled trials,” he said, adding “substantial numbers of patients in this situation continue to be treated with combination therapy, which indicates a gap between guidelines and clinical practice.”
The Atrial Fibrillation and Ischemic events with Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE), he said, was designed to address this practice gap, randomizing 2,200 individuals to receive monotherapy with rivaroxaban or combination therapy. A total of 1,973 patients completed follow-up.
Patients were included in the randomized, open-label, parallel-group trial if they had AFib and stable CAD and were more than 1 year out from revascularization, or if they had angiographically confirmed CAD that did not need revascularization. All 294 AFIRE study sites were in Japan.
The study’s primary endpoint for efficacy was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and all-cause death.
Most of the patients (79%) were male, and the mean age was 74 years. About 70% of patients in each treatment arm had received prior PCI, and 11% had undergone previous coronary artery bypass grafting (CABG).
The monotherapy arm received rivaroxaban 10 or 15 mg once daily depending on renal status. Patients in the combination therapy arm received rivaroxaban, plus a single antiplatelet drug. This could be 81 or 100 mg aspirin daily, clopidogrel at 50 or 75 mg/day, or prasugrel at 2.5 or 3.5 mg/day.
On the recommendation of the data and safety monitoring committee, the trial was terminated about 3 months early because significantly more all-cause deaths were being seen in the combination therapy group, said Dr. Yasuda. In the end, patients were treated under the study protocol for a median 23 months and followed up for a median 24.1 months.
Kaplan-Meier estimates for the first occurrence of the composite efficacy endpoint showed that monotherapy had a rate of 4.14% per patient-year, while combination therapy had a rate of occurrence for the efficacy endpoint of 5.75% per patient-year.
These figures yielded a statistically significant hazard ratio (HR) of 9.72 favoring monotherapy (P less than .001) for the prespecified noninferiority endpoint. In a post hoc analysis, rivaroxaban monotherapy achieved superiority over dual therapy (P = .02).
Breaking down the composite efficacy endpoint into its constituents, deaths by any cause and cardiovascular deaths primarily drove the difference in treatment arms. Seventy-three patients in the combo therapy arm and 41 in the rivaroxaban arm died of any cause, and the cause of death was cardiovascular for 43 combination therapy patients and 26 monotherapy patients. This yielded HRs favoring rivaroxaban of 0.55 for all-cause mortality and 0.59 for cardiovascular deaths.
Hazard ratios for individual cardiovascular events were not statistically significantly different between treatment arms, except for hemorrhagic stroke, which was seen in 13 patients receiving dual therapy and 4 receiving rivaroxaban alone, for a hazard ratio of 0.30.
Rivaroxaban monotherapy also bested dual therapy in safety: The HR was 0.59 for the incidence of a major bleed on rivaroxaban versus combination therapy, using International Society on Thrombosis and Haemostasis–established criteria for major bleeding. In the dual therapy arm, 58 individuals experienced major bleeding – the study’s primary safety endpoint – compared with 35 in the monotherapy arm, for a hazard ratio of 0.59; nonmajor bleeding occurred in 198 dual therapy patients and 121 monotherapy patients, yielding a hazard ratio of 0.58.
The Kaplan-Meier estimate for major bleeding on monotherapy was 1.62% per patient-year, compared with 2.76% per patient-year for those on combination therapy. These findings, said Dr. Yasuda, were “generally” consistent across prespecified subgroups that included participant stratification by age, sex, and bleeding risk, among others.
Dr. Yasuda acknowledged the many limitations of the trial. First, early termination introduced the possibility of overestimating the benefit of rivaroxaban monotherapy. Indeed, said Dr. Yasuda, “the reductions in rate of ischemic events and death from any cause with rivaroxaban monotherapy were unanticipated and are difficult to explain.”
Furthermore, the open-label trial design could be a source of bias and the use of both aspirin and P2Y12 inhibitors for antiplatelet therapy “makes it uncertain whether the benefit of rivaroxaban monotherapy applies equally to the two combination regimens,” said Dr. Yasuda.
Rivaroxaban dosing in AFIRE was tailored to the Japanese study population, noted Dr. Yasuda. This means that the study is not immediately generalizable to non-Asian populations, needing replication before fully closing the knowledge gap about best long-term management of patients with AFib and stable CAD in the United States and Western Europe.
However, Dr. Yasuda pointed out, serum rivaroxaban levels in Japanese patients taking the 10- or 15-mg dose are generally similar to those seen in white patients taking a 20-mg rivaroxaban dose.
Freek Verheugt, MD, of Onze Lieve Vrouwe Gasthuis Hospital, Amsterdam, was the discussant for the presentation. He raised an additional concern: “East Asian patients are poor metabolizers of clopidogrel, which may have resulted also in underestimation of bleeding.” He cautioned that the AFIRE results may not be applicable to patients on a novel anticoagulant other than clopidogrel, or on vitamin K antagonists.
In his detailed critique of the AFIRE results, Dr. Verheugt cited the OAC ALONE trial, which used a similar study design and was also conducted in Japan. For OAC ALONE, Dr. Verheugt pointed out that “You can see ... that it was not harmful in this 700-patient study to stop aspirin therapy 1 year after an intervention.” However, he said, “the net clinical benefit is not very different, either” between treatment arms in the OAC ALONE trial. “Given the low number of patients and the low number of events, this trial was not conclusive whatsoever” he added, so AFIRE’s findings were needed.
The safety data from AFIRE, with a study population triple that of OAC ALONE, makes the safety argument for monotherapy “a very easy winner,” said Dr. Verheugt.
Dr. Verheugt was not mystified by the lower all-cause and cardiovascular death rate in the monotherapy group. “What are the mechanisms that if you stop antiplatelet therapy you have a better ischemic outcome? How come?” asked Dr. Verheugt.
“Very likely, it is the bleeding ... that you prevent if you stop antiplatelet therapy,” he said, adding that it’s known from previous studies in individuals with acute coronary syndromes and AFib that “bleeding is correlated with mortality, and that’s also proven here.”
Though Dr. Verheugt joined Dr. Yasuda in calling for replication of the results in a non-Asian population, he concurred that the AFIRE results validate current practice for anticoagulation in AFib with stable CAD. “Stopping at 1 year is safer than continuation and, most of all, it saves lives,” he said.
Full results of AFIRE were published online at the time of Dr. Yasuda’s presentation (N Engl J Med. 2019 Sep 2. doi: 10.1056/NEJMoa1904143).
The study was funded by the Japanese Cardiovascular Research Foundation. Dr. Yasuda reported financial relationships with Abbott, Bristol-Myers, Daiichi-Sankyo, and Takeda. Dr. Verheugt reported financial relationships with BayerHealthcare, BMS/Pfizer, Boehringer-Ingelheim, and Daiichi-Sankyo.
SOURCE: Yasuda S. et al. ESC 2019, Hot Line Session 3, Abstract 3175.
AT THE ESC CONGRESS 2019
Dapagliflozin given Fast Track status for HF therapy
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
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