Efficacy and Safety of Direct Oral Anticoagulants in Patients with Diabetes and Nonvalvular Atrial Fibrillation: Meta-Analysis of Observational Studies
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ABSTRACT: Background
This meta-analysis was performed to compare the efficacy and safety of direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) for stroke prevention in real-world patients with diabetes and nonvalvular atrial fibrillation (NVAF) through observational studies. Methods
PubMed, Embase, and Web of Science databases were searched up to August 2020 for eligible studies. Outputs were presented as risk ratios (RRs) and corresponding 95% confidence intervals (CIs) by using a random-effect model. Results
Seven observational studies involving 249,794 diabetic NVAF patients were selected. Compared with VKAs, the use of DOACs was associated with significantly reduced risks of stroke (RR = 0.56, 95% CI 0.45-0.70; p < 0.00001), ischemic stroke (RR = 0.61, 95% CI 0.48-0.78; p < 0.0001), stroke or systemic embolism (SSE) (RR = 0.81, 95% CI 0.68-0.95; p = 0.01), myocardial infarction (RR = 0.69, 95% CI 0.55-0.88; p = 0.002), major bleeding (RR = 0.75, 95% CI 0.63-0.90; p = 0.002), intracranial hemorrhage (RR = 0.50, 95% CI 0.44-0.56; p < 0.00001), and major gastrointestinal bleeding (RR = 0.77, 95% CI 0.62-0.95; p = 0.02), and a borderline significant decrease in major adverse cardiac events (RR = 0.87, 95% CI 0.75-1.00; p = 0.05) in NVAF patients with diabetes. Conclusion
For patients with NVAF and diabetes in real-world clinical settings, DOACs showed superior efficacy and safety profile over VKAs and significantly reduced risks of stroke, ischemic stroke, SSE, myocardial infarction, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding.
SUBMITTER: Cao B
PROVIDER: S-EPMC8523231 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285?292 patients were included in the 6 matched cohorts: 57?929 apixaban-warfarin, 26?838 dabigatran-warfarin, 83?007 rivaroxaban-warfarin, 27?096 apixaban-dabigatran, 62?619 apixaban-rivaroxaban, and 27?538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.
| S-EPMC6257512 | biostudies-literature
Project description:The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.
| S-EPMC6490750 | biostudies-literature
Project description:BackgroundDirect oral anticoagulants (DOACs) have widely replaced warfarin for stroke prevention in nonvalvular atrial fibrillation. Our objective was to compare the safety and effectiveness of DOACs (dabigatran, rivaroxaban, apixaban) versus warfarin for stroke prevention in nonvalvular atrial fibrillation in the Canadian setting.MethodsWe conducted a population-based observational multicentre cohort study with propensity score matching and subsequent meta-analysis. We used health care databases from 7 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec and Nova Scotia). Patients with nonvalvular atrial fibrillation who initiated anticoagulation therapy in 2009-2017 were matched to an equal number who initiated warfarin. The primary outcome was the pooled hazard ratio (HR) for ischemic stroke or systemic embolization. Secondary outcomes included pooled HRs for major bleeding; a composite outcome of stroke, systemic embolization, major bleeding and all-cause mortality; and myocardial infarction. We modelled HRs using proportional hazard Cox regression with inverse probability of censoring weights, and estimated pooled HRs with random-effect meta-analyses.ResultsWe included 128 273 patients who initiated anticoagulation with a DOAC (40 503 dabigatran, 49 498 rivaroxaban and 38 272 apixaban) and 128 273 patients who initiated anticoagulation with warfarin. The pooled HR for ischemic stroke or systemic embolization comparing DOACs to warfarin was 1.02 (95% confidence interval [CI] 0.87 to 1.19). Direct oral anticoagulants were associated with lower rates of major bleeding (pooled HR 0.81, 95% CI 0.69 to 0.97), the composite outcome (pooled HR 0.81, 95% CI 0.74 to 0.89) and all-cause mortality (pooled HR 0.81, 95% CI 0.78 to 0.85).InterpretationIn this real-world study, DOACs were associated with similar risks of ischemic stroke or systemic embolization, and lower risks of bleeding and total mortality compared to warfarin. These findings support the use of DOACs for anticoagulation in nonvalvular atrial fibrillation.Trial registrationClinicalTrials.gov, no. NCT03596502.
| S-EPMC7759115 | biostudies-literature
Project description:BackgroundPatients with cancer are more likely to develop nonvalvular atrial fibrillation (NVAF). Currently there are no definitive clinical trials or treatment guidelines for NVAF patients with concurrent cancer.ObjectivesThis subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (stroke/SE) and major bleeding (MB) among NVAF patients with active cancer who were prescribed non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin.MethodsA retrospective observational study was conducted in NVAF patients with active cancer who newly initiated apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, through September 30, 2015, with the use of Medicare and 4 U.S. commercial claims databases. Cox models were used to estimate the risk of stroke/SE and MB in the pooled propensity score-matched cohorts.ResultsA total of 40,271 patients were included, with main cancer types of prostate (29%), female breast (17%), genitourinary (14%), and lung (13%). Compared with warfarin, apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.45-0.78) and MB (HR: 0.58; 95% CI: 0.50-0.68); dabigatran and rivaroxaban had similar risks of stroke/SE (dabigatran: HR: 0.88 [95% CI: 0.54-1.41]; rivaroxaban: HR: 0.82 [95% CI: 0.62-1.08]) and MB (dabigatran: HR: 0.76 [95% CI: 0.57-1.01]; rivaroxaban: HR: 0.95 [95% CI: 0.85-1.06]). Risks of stroke/SE and MB varied among NOAC-NOAC comparisons, while consistent treatment effects were seen for all treatment comparisons across key cancer types.ConclusionsAmong this cohort of NVAF patients with active cancer, the risk of stroke/SE and MB varied among oral anticoagulants and were consistent across cancer types.
| S-EPMC8463723 | biostudies-literature
Project description:Background and purposeThe effects of direct oral anticoagulants in nonvalvular atrial fibrillation should be assessed in actual conditions of use. France has near-universal healthcare coverage with a unified healthcare information system, allowing large population-based analyses. NAXOS (Evaluation of Apixaban in Stroke and Systemic Embolism Prevention in Patients With Nonvalvular Atrial Fibrillation) aimed to compare the safety, effectiveness, and mortality of apixaban with vitamin K antagonists (VKAs), rivaroxaban, and dabigatran, in oral anticoagulant-naive patients with nonvalvular atrial fibrillation.MethodsThis was an observational study using French National Health System claims data and including all adults with nonvalvular atrial fibrillation who initiated oral anticoagulant between 2014 and 2016. Outcomes of interest were major bleeding events leading to hospitalization (safety), stroke and systemic thromboembolic events (effectiveness), and all-cause mortality. Four approaches were used for comparative analyses: matching on propensity score (PS; 1:n); as a sensitivity analysis, matching on high-dimensional PS; adjustment on PS; and adjustment on known confounders. For each outcome, cumulative incidence rates accounting for competing risks of death were estimated.ResultsOverall, 321 501 patients were analyzed, of whom 35.0%, 27.2%, 31.1%, and 6.6% initiated VKAs, apixaban, rivaroxaban, and dabigatran, respectively. Apixaban was associated with a lower PS-matched risk of major bleeding compared with VKAs (hazard ratio [HR], 0.43 [95% CI, 0.40-0.46]) and rivaroxaban (HR, 0.67 [95% CI, 0.63-0.72]), but not dabigatran (HR, 0.93 [95% CI, 0.81-1.08]). Apixaban was associated with a lower risk of stroke and systemic thromboembolic event compared with VKAs (HR, 0.60 [95% CI, 0.56-0.65]), but not rivaroxaban (HR, 1.05 [95% CI, 0.97-1.15]) or dabigatran (HR, 0.93 [95% CI, 0.78-1.11]). All-cause mortality was lower with apixaban than with VKAs, but not lower than with rivaroxaban or dabigatran.ConclusionsApixaban was associated with superior safety, effectiveness, and lower mortality than VKAs; with superior safety than rivaroxaban and similar safety to dabigatran; and with similar effectiveness when compared with rivaroxaban or dabigatran. These observational data suggest potentially important differences in outcomes between direct oral anticoagulants, which should be explored in randomized trials.
| S-EPMC7306262 | biostudies-literature
Project description:OBJECTIVES:Older adult patients are underrepresented in clinical trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin. This subgroup analysis of the ARISTOPHANES study used multiple data sources to compare the risk of stroke/systemic embolism (SE) and major bleeding (MB) among very old patients with nonvalvular atrial fibrillation (NVAF) prescribed NOACs or warfarin. DESIGN:Retrospective observational study. SETTING:The Centers for Medicare & Medicaid Services and three US commercial claims databases. PARTICIPANTS:A total of 88 582 very old (aged ≥80 y) NVAF patients newly initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015. MEASUREMENTS:In each database, six 1:1 propensity score matched (PSM) cohorts were created for each drug comparison. Patient cohorts were pooled from all four databases after PSM. Cox proportional hazards models were used to estimate hazard ratios (HRs) of stroke/SE and MB. RESULTS:The patients in the six matched cohorts had a mean follow-up time of 7 to 9 months. Compared with warfarin, apixaban (HR = .58; 95% confidence interval [CI] = .49-.69), dabigatran (HR = .77; 95% CI = .60-.99), and rivaroxaban (HR = .74; 95% CI = .65-.85) were associated with lower risks of stroke/SE. For MB, apixaban (HR = .60; 95% CI = .54-.67) was associated with a lower risk; dabigatran (HR = .92; 95% CI = .78-1.07) was associated with a similar risk, and rivaroxaban (HR = 1.16; 95% CI = 1.07-1.24) was associated with a higher risk compared with warfarin. Apixaban was associated with a lower risk of stroke/SE and MB compared with dabigatran (stroke/SE: HR = .65; 95% CI = .47-.89; MB: HR = .60; 95% CI = .49-.73) and rivaroxaban (stroke/SE: HR = .72; 95% CI = .59-.86; MB: HR = .50; 95% CI = .45-.55). Dabigatran was associated with a lower risk of MB (HR = .77; 95% CI = .67-.90) compared with rivaroxaban. CONCLUSION:Among very old NVAF patients, NOACs were associated with lower rates of stroke/SE and varying rates of MB compared with warfarin. J Am Geriatr Soc 67:1662-1671, 2019.
| S-EPMC6852415 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; e.g., warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (e.g., those with renal impairment) and other specific clinical situations.
| S-EPMC4468938 | biostudies-other
Project description:Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide and the main cause of anticoagulation, being direct oral anticoagulants (DOAC) increasingly used in this context. On the other hand, obesity is a known risk thromboembolic factor. In the clinical trials that led to the approval of DOAC for ischemic stroke prevention, patients with morbid obesity were underrepresented. The International Society of Thrombosis and Haemostasis suggests not using these drugs in morbid obese patients. Thus, the primary objectives of this study were to analyse the rates of mortality, thrombotic and haemorrhagic events in patients with morbid obesity. As secondary objectives, factors statistically associated with these events were analysed. Methods: multicentre retrospective study that included patients diagnosed with AF on treatment with DOAC from January 2013 to December 2016. The subgroup of patients with morbid obesity (BMI > 40 and / or weight > 120 kg) was analysed. Mean follow-up was 1.7 years. Results: Amongst 2,492 patients included in the study, 135 patients had morbid obesity (mean age was 71 ± 11 years). The mean scores of the CHA2DS2-VASc and HAS-BLED risk scales were 3.7 ± 1.6 and 2.2 ± 0.9, respectively. Neither differences were found regarding mortality (5.2 vs 6/100 patient-years, p = 0.662), ischemic stroke (0.8 vs 1.9/100 patient-years, p = 0.261) and major bleeding rates (3 vs 3.1/100 patient-years, p = 0.983) between morbidly obese population and general population. Nor was there an association found between the degree of obesity and any of the events studied. Conclusion: DOAC are safe and effective in morbidly obese patients.
| S-EPMC8603013 | biostudies-literature
Project description:There are few head-to-head trials directly comparing non-vitamin K antagonist oral anticoagulants (NOACs) against one other. A network meta-analysis (NMA) was performed to examine the indirect comparisons among NOACs in Asians with nonvalvular atrial fibrillation (NVAF). STATA 15.0 and ADDIS 1.16.8 softwares were used to perform the statistical analysis. Odds ratios with 95% credible intervals were applied to evaluate the end points. The probabilities of treatment rank were used to understand which interventions are more effective and safe, and the total rank probability was 1. In our NMA, the rank probabilities of apixaban in the case of stroke or systemic embolism, death from any cause, major bleeding, and intracranial hemorrhage (ICH) were 0.47, 0.49, 0.42, and 0.51, respectively. For cases of myocardial infarction, the rank probabilities of rivaroxaban were 0.40. This NMA indirectly compares the main efficacy and safety end points among NOACs in Asians with NVAF, and the rank probability analysis showed that apixaban likely performs best in cases of stroke or systemic embolism, death from any cause, and ICH; rivaroxaban may have the best performance for myocardial infarction.
| S-EPMC7019404 | biostudies-literature
Project description:INTRODUCTION: Oral anticoagulants (OAs) are significantly more effective than Aspirin in the prevention of cerebrovascular accidents among patients with atrial fibrillation (AF). Several studies, however, showed OAs to be widely underused in these patients. OBJECTIVE: To assess the appropriateness of antithrombotic therapy in an Italian population of AF patients. METHODS: Two hundred and fifty-five consecutive patients affected by nonvalvular AF participated in the study. Data were collected on demographic characteristics, risk factors for stroke, current prophylactic therapy, and perceived or actual risk factors for bleeding. INR levels were measured. Patients were stratified by their risk for stroke (214 at high risk, 21 moderate, 20 low), and their prophylactic therapy was analysed in light of international antithrombotic therapy recommendations. After therapy adjustment, 203 of our patients were followed-up for the occurrence of cerebrovascular events for an average of 27 months. RESULTS: Upon admission, 35% (n=75) of patients in the high-risk category were either taking no antithrombotic prophylaxis or were being treated with Aspirin. In addition, 38 of 139 patients receiving OAs had an INR<2. Thus, a total of 113 (52.8%) high-risk subjects were not receiving adequate antithrombotic therapy. Of high-risk patients not treated with OAs, 46.7% reported no perceived or actual risk factors for bleeding. The annual incidence of cerebrovascular accidents was 3.8% among 163 high-risk patients assigned to OA treatment, and 4.5% among 39 patients given Aspirin treatment. Relative to expected annual incidence rates, cerebrovascular risk in anticoagulated patients was reduced by about 70%. CONCLUSIONS: Underuse of OAs is still common in Italy, and much of it cannot be explained by the concern for haemorrhage. Support and training in the complex task of anticoagulation management may help to extend this efficacious prophylactic therapy to all patients who may benefit from it.
| S-EPMC2780607 | biostudies-other