Effectiveness and Safety of DOACs vs. Warfarin in Patients With Atrial Fibrillation and Frailty: A Systematic Review and Meta-Analysis.
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ABSTRACT: Background
Patients with atrial fibrillation (AF) and frailty are a considerable group in clinical practice. However, existing studies provide insufficient evidence of anticoagulation strategies for these patients. Therefore, we conducted a meta-analysis to determine the effectiveness and safety outcomes of direct oral anticoagulants (DOACs) for these patients.Methods
Randomized controlled trials or observational studies reporting the data about the DOACs and warfarin therapy among frail AF patients were included. The search was performed in the PubMed and Embase databases up to March 2022. Frailty was defined using the most widely used claims-based frailty index or the cumulative deficit model-based frailty index.Results
A total of 4 studies involving 835,520 patients were included. Compared with warfarin, DOACs therapy reduced the risks of stroke or systemic embolism (HR = 0.79, 95%CI: 0.69-0.90), ischemic stroke (HR = 0.79, 95%CI: 0.71-0.87), hemorrhagic stroke (HR = 0.52, 95%CI: 0.35-0.76), and all-cause death (HR = 0.90, 95%CI: 0.84-0.96). In safety outcomes, DOACs was significantly associated with reduced risks of major bleeding (HR = 0.79, 95%CI: 0.64-0.97) and intracranial hemorrhage (HR = 0.58, 95%CI: 0.52-0.65) compared to warfarin, but there were no statistically differences in gastrointestinal bleeding (HR = 0.97, 95%CI: 0.73-1.29).Conclusions
DOACs exerted superior effectiveness and safety outcome than warfarin in AF patients with frailty.
SUBMITTER: Zeng S
PROVIDER: S-EPMC9263568 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundObese patients are underrepresented in clinical trials assessing the comparative effectiveness and safety of use of direct oral anticoagulants vs use in atrial fibrillation (AF) patients.MethodsUsing data from Quebec provincial administrative databases, for the years2010-2017, we created a retrospective cohort of patients with inpatient or outpatient coding for AF and obesity who were newly prescribed an oral anticoagulant. The primary safety outcome was a composite of intracranial, gastrointestinal, and major bleeding from other sites, and the primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, acute myocardial infarction, and death in the first year after oral anticoagulant initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models.ResultsA total of 2263 patients were included, of whom 1253, 403, and 539 filled a warfarin, standard-dose rivaroxaban, and standard-dose apixaban prescription, respectively. Standard-dose rivaroxaban was associated with a similar composite safety (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.44-1.91) and composite effectiveness risk (HR 1.42; 95% CI 0.99-2.04) compared to warfarin, whereas standard-dose apixaban was associated with a lower composite safety (HR 0.40; 95% CI 0.16-0.98) and similar composite effectiveness risk (HR 0.96; 95% CI 0.67-1.39).ConclusionUse of direct oral anticoagulants in obese AF patients was associated with a similar effectiveness and safety profile to that of warfarin use.
| S-EPMC9039573 | biostudies-literature
Project description:BackgroundDirect oral anticoagulants (DOACs) have increasingly become an alternative to warfarin in atrial fibrillation (AF) patients. Nonetheless, data on the effectiveness and safety of DOACs in periprocedural of catheter ablation (CA) in real-world practice was relatively rare.Methods and results3385 AF patients underwent initial CA and never used oral anticoagulant before enrollment between April 2013 and December 2018 were involved from China Atrial Fibrillation (China-AF) Registry. Warfarin, rivaroxaban and dabigatran were used in 1896 (56.0%), 718 (21.2%), and 771 (22.8%) patients, respectively. Propensity score matching was used to balance covariates across study groups. No significant differences were observed in rivaroxaban-warfarin, dabigatran-warfarin and dabigatran-rivaroxaban cohort for thromboembolic (TE) and major bleeding (MB) incidence. Similar results were also revealed in low-dose rivaroxaban (RLD)-warfarin, low-dose dabigatran (DLD)-warfarin and DLD-RLD cohort. However, the risk of non-MB was higher not only on standard-dose of rivaroxaban but also on RLD when compared with warfarin and with DLD, respectively.ConclusionsIn this study, the incidence of TE and MB were both comparable in standard- or low-dose DOACs versus warfarin and between the two DOACs, whereas the risk of non-MB was higher in rivaroxaban than in warfarin and in RLD than in DLD.
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Project description:ObjectiveTo compare the cost-effectiveness of apixaban vs warfarin for secondary stroke prevention in patients with atrial fibrillation (AF).MethodsUsing standard methods, we created a Markov decision model based on the estimated cost of apixaban and data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and other trials of warfarin therapy for AF. We quantified the cost and quality-adjusted life expectancy resulting from apixaban 5 mg twice daily compared with those from warfarin therapy targeted to an international normalized ratio of 2-3. Our base case population was a cohort of 70-year-old patients with no contraindication to anticoagulation and a history of stroke or TIA from nonvalvular AF.ResultsWarfarin therapy resulted in a quality-adjusted life expectancy of 3.91 years at a cost of $378,500. In comparison, treatment with apixaban led to a quality-adjusted life expectancy of 4.19 years at a cost of $381,700. Therefore, apixaban provided a gain of 0.28 quality-adjusted life-years (QALYs) at an additional cost of $3,200, resulting in an incremental cost-effectiveness ratio of $11,400 per QALY. Our findings were robust in univariate sensitivity analyses varying model inputs across plausible ranges. In Monte Carlo analysis, apixaban was cost-effective in 62% of simulations using a threshold of $50,000 per QALY and 81% of simulations using a threshold of $100,000 per QALY.ConclusionsApixaban appears to be cost-effective relative to warfarin for secondary stroke prevention in patients with AF, assuming that it is introduced at a price similar to that of dabigatran.
| S-EPMC3525294 | biostudies-literature
Project description:BackgroundCurrent guidelines recommend the utilization of direct-acting oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF). However, the optimal anticoagulation strategy for AF patients with bioprosthetic heart valves (BPHV) remains controversial. Therefore, we conducted this meta-analysis to explore the effect of DOACs versus vitamin K antagonists (VKAs) in this population.MethodsWe systematically searched the PubMed and Embase databases until November 2021 for studies reporting the effect of DOACs versus VKAs in AF patients with BPHV. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using the random-effects model with an inverse variance method.ResultsWe selected four randomized clinical trials and seven observational studies (2236 DOAC- and 6403 VKAs-users). Regarding the effectiveness outcomes, there were no significant differences between DOACs and VKAs in stroke or systemic embolism (RR = 0.74, 95%CI: 0.50-1.08), ischemic stroke (RR = 1.08, 95%CI: 0.76-1.55), all-cause death (RR = 0.98, 95%CI: 0.86-1.12), and cardiovascular death (RR = 0.85, 95%CI: 0.40-1.80). In terms of the safety outcomes, DOACs was associated with lower risks of major bleeding (RR = 0.70, 95%CI: 0.59-0.82) and intracranial bleeding (RR = 0.42, 95%CI: 0.26-0.70), but the risks of any bleeding (RR = 0.85, 95%CI: 0.65-1.13) and gastrointestinal bleeding (RR = 0.92, 95%CI: 0.73-1.17) are not significantly different when compared with VKAs. The subgroup analysis with follow-up as a covariate revealed that the DOACs had lower risks of SSE (RR = 0.59, 95%CI: 0.37-0.94) and major bleeding (RR = 0.69, 95%CI: 0.58-0.81) in patients with a mean follow-up of more than 24 months, but no statistical differences were found in patients with the follow-up less than 24 months (SSE: RR = 1.10, 95%CI: 0.92-1.32; major bleeding: RR = 0.91, 95%CI: 0.42-2.01).ConclusionsIn AF with BPHV, patients on DOACs experienced a reduced risk of major bleeding and intracranial bleeding compared with VKAs, while the risks of stroke, cardiovascular death, and all-cause mortality were similar.
| S-EPMC9248967 | biostudies-literature
Project description:Background: Patients with active peptic ulcer (PU) were excluded from direct oral anticoagulant (DOAC) trials for stroke prevention in patients with atrial fibrillation (AF). This study evaluated the safety and effectiveness of DOACs in AF patients with active, inactive and no peptic ulcer (PU). Methods: This study accessed electronic medical records from January 1, 2009 to May 31, 2019 at a multi-center healthcare provider in Taiwan and involved 2,955 AF patients who had undergone esophagogastroduodenoscopy ≤ 1 year before anticoagulation. Subjects were classified into 3 groups: active (n = 237), inactive (n = 828) and no-PU (n = 1,890) groups. We compared the risks of major bleeding, gastrointestinal bleeding, and ischemic stroke/systemic embolism (IS/SE) between DOACs and warfarin among the 3 groups. Results: In the active PU group, there were no significant differences in the risks of major bleeding [hazard ratio (HR) = 0.65, 95% confidence interval (CI) 0.08-4.98, p = 0.676], gastrointestinal bleeding (HR = 0.65, 95% CI 0.08-4.98, p = 0.676) and IS/SE (HR = 2.58; 95% CI 0.53-12.70, p = 0.243) between DOAC and warfarin (as the reference). In the inactive PU group, there were no significant differences in the risks of major bleeding (HR = 0.36, 95% CI 0.09-1.39, p = 0.138), gastrointestinal bleeding (HR = 0.21, 95% CI 0.02-1.80, p = 0.153), and IS/SE (HR = 1.04, 95% CI 0.39-2.82, p = 0.934) between DOAC and warfarin (as the reference). In the no-PU group, DOACs were associated with lower risk of major bleeding (HR = 0.26, 95% CI 0.12-0.53, p < 0.001), gastrointestinal bleeding (HR = 0.25, 95% CI 0.01-0.59, p = 0.002), and similar risk of IS/SE (HR = 0.92, 95% CI 0.55-1.54, p = 0.757) compared to warfarin. Conclusions: DOACs were as effective as warfarin in preventing IS/SE irrespective of PU status and safer than warfarin in reducing major bleeding in the no-PU group. In patients with active or inactive PUs, DOAC and warfarin were not significantly different in their effects on major bleeding or gastrointestinal bleeding.
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Project description:Background The use of Direct Oral Anticoagulants (DOACs) in patients who have both atrial fibrillation (AF) and end-stage renal disease (ESRD) requiring hemodialysis remains controversial, with warfarin remaining the mainstay of the treatment. As hemodialysis patients were excluded from most clinical DOACs trials, the evidence of their efficacy and safety is lacking in this cohort of patients. Aim To review the current evidence investigating safety profile and the efficacy of DOACs in comparison with warfarin in patients with AF and end-stage renal disease (ESRD) requiring hemodialysis. Methods and Results We included five studies with a total of 34,516 patients in our meta-analysis. The outcomes were major bleeding, ischemic stroke, systemic embolization, hemorrhagic stroke, gastrointestinal bleeding, minor bleeding, and death. Of these patients, 31,472 (92.14%) received warfarin and 3,044 patients received DOACs (8.91%). No significant differences in the incidence of hemorrhagic stroke, major bleeding, hemodialysis access site bleeding, ischemic stroke, and GI bleeding were found between DOACs and warfarin. However, there were higher rates of systemic embolization, minor bleeding, and death events in patients who received DOACs than in the warfarin group (3.39% vs. 1.97%, P-value = 0.02), (6.78% vs. 2.2%, P-value 0.02), and (11.38% vs. 5.12%, P-value < 0.006) respectively. Conclusion In patients on dialysis who require anticoagulation for AF, warfarin could be associated with a significant reduction in minor bleeding, systemic embolization, and death compared to DOACs. These findings need to be validated by further prospective studies to address the best strategy to deal with the increased thrombotic and bleeding risks in such patients.
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Project description:Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies. Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR). Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke [hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61-0.70; p < 0.0001] and major bleeding (HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61-0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49-0.69; p < 0.0001, respectively. Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke.
| S-EPMC10687440 | biostudies-literature
Project description:Background Guideline recommendations on the use of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with aortic stenosis are based on studies including a low number of patients with aortic stenosis. The aim of this study was to estimate the effects of NOAC versus warfarin on thromboembolism and major bleeding among AF patients with aortic stenosis. Methods and Results We emulated a target trial using observational data from Danish nationwide registries between 2013 and 2018. Thromboembolism was defined as a hospital diagnosis of ischemic stroke and/or systemic embolism, and major bleeding was defined as a hospital diagnosis of intracranial bleeding, gastrointestinal bleeding, or major or clinically relevant bleeding in other anatomic sites. Treatment effect estimates were based on an intention-to-treat and per-protocol approach. A total of 3726 patients with AF and aortic stenosis claimed a prescription for either a NOAC (2357 patients) or warfarin (1369 patients) and met the eligibility criteria for the trial. During 3 years of follow-up, the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08-2.45) and 0.73 (0.59-0.91) for NOAC compared with warfarin in the intention-to-treat analyses. Similar results were observed in the per-protocol analyses. Conclusions In this observational study, we observed a higher risk of thromboembolism but a lower risk of major bleeding for treatment with NOACs compared with warfarin in patients with AF and aortic stenosis. This observation needs confirmation in large randomized trials in these commonly encountered patients.
| S-EPMC9075348 | biostudies-literature
Project description:IntroductionCurrent evidence regarding the clinical outcomes of non-vitamin K oral anticoagulants (NOACs) versus warfarin in patients with atrial fibrillation (AF) and previous stroke is inconclusive, especially in patients with previous intracranial haemorrhage (ICrH). We aim to undertake a systematic review and meta-analysis assessing the effectiveness and safety of NOACs versus warfarin in AF patients with a history of stroke.MethodsWe searched studies published up to December 10, 2022, on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials. Studies on adults with AF and previous ischaemic stroke (IS) or IrCH receiving either NOACs or warfarin and capturing outcome events (thromboembolic events, ICrH, and all-cause mortality) were eligible for inclusion.ResultsSix randomized controlled trials (RCTs) (including 19,489 patients with previous IS) and fifteen observational studies (including 132,575 patients with previous IS and 13,068 patients with previous ICrH) were included. RCT data showed that compared with warfarin, NOACs were associated with a significant reduction in thromboembolic events (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.75-0.96), ICrH (OR: 0.57, 95% CI: 0.36-0.90), and all-cause mortality (OR: 0.88, 95% CI: 0.80-0.98). In analysing observational studies, similar results were retrieved. Moreover, patients with previous ICrH had a lower OR on thromboembolic events than those with IS (OR: 0.66, 95% CI: 0.46-0.95 vs. OR: 0.80, 95% CI: 0.70-0.93) in the comparison between NOACs and warfarin.ConclusionsObservational data showed that in AF patients with previous stroke, NOACs showed better clinical performance compared to warfarin and the benefits of NOACs were more pronounced in patients with previous IrCH versus those with IS. RCT data also showed NOACs are superior to warfarin. However, current RCTs only included AF patients who survived an IS, and further large RCTs focused on patients with previous ICrH are warranted.
| S-EPMC10836928 | biostudies-literature
Project description:Background: Edoxaban is a novel oral anticoagulant which may decrease the risk of stroke and systemic embolism in patients suffering from atrial fibrillation (AF). However, the decreased efficacy of edoxaban versus warfarin for the avoidance of stroke and systemic embolism in AF with creatinine clearance (CrCl) > 95 mL/min has been reported. The purpose of this meta-analysis is to further clarify the safety (major bleeding) and efficacy (stroke or systemic embolism) of edoxaban for AF patients with various CrCl. Methods: A systematic search of studies on edoxaban and warfarin in AF patients related to renal function was conducted in PubMed, Medline, Web of Science databases, EBSCO, Embase, and the Cochrane Central Register of Controlled Trials. In this meta-analysis (protocol number: PROSPERO CRD 42021245512), we included studies that provide specific data on three outcomes: ischemic stroke or systemic embolism (S/SE), bleeding, and all-cause mortality. Results: This meta-analysis enrolled two randomized controlled trials (RCTs) studies and two retrospective studies that enrolled 28,065 patients. According to CrCl, subjects are divided into three groups (CrCl 30−50 mL/min, CrCl 50−95 mL/min, CrCl > 95 mL/min). In AF patients with CrCl 30−50 mL/min, edoxaban 30 mg daily is similar to warfarin in the prevention of ischemic S/SE and all-cause mortality, resulting in lower bleeding rate and better net clinical outcome (ischemic S/SE: hazard ratio (HR), 0.85, 95% confidence interval (CI), 0.19−1.87; all-cause mortality: HR, 0.65, 95% CI, 0.35−1.19; bleeding: HR, 0.75, 95% CI, 0.60−0.93; net clinical outcome: HR, 0.75, 95% CI, 0.63−0.90). In the group of CrCl 50−95 mL/min, the net clinical outcome was more favorable with edoxaban 60 mg daily than warfarin (HR, 0.81, 95% CI: 0.68−0.96), and there was no significant difference between edoxaban 60 mg daily and warfarin in terms of prevention of bleeding, ischemic S/SE, and all-cause mortality. For AF patients with CrCl > 95 mL/min, there was a statistically significant difference in lower bleeding rate between edoxaban 60 mg daily and warfarin (bleeding: HR: 0.70, 95% CI: 0.58−0.84). There was no differential safety in ischemic S/SE, all-cause mortality, and net clinical outcome. Conclusion: Overall, edoxaban was superior to warfarin in terms of net clinical outcome in various groups of CrCl with AF patients. Although there was no significant difference in net clinical outcome between edoxaban and warfarin for AF patients with CrCl > 95 mL/min, edoxaban is not inferior to warfarin in safety and effectiveness in the various levels of CrCl. Edoxaban may be a more effective and safe treatment than warfarin for patients with chronic kidney disease (CKD) who require anticoagulation. More high-quality and long-term clinical research are needed to further estimate the effects of edoxaban.
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