Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies

Abstract

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

Comparison of readmissions among hospitalized nonvalvular atrial fibrillation patients treated with oral anticoagulants in the United States

“…For this study we specifically were concerned with hospital readmission outcomes, but our findings between the warfarin and apixaban cohorts and the rivaroxaban and apixaban cohorts provide further evidence that apixaban treatment may be associated with better clinical outcomes than these other OACs. These findings are aligned with those of several real-world evidence studies [9][10][11][12][13][14][15][16][17][18][19] , as well as network meta-analyses of clinical trial data 23,24 , in which all have generally found apixaban to have the better safety profile (i.e. lowest bleeding risk) compared to other OACs.…”

“…A network meta-analysis published in 2018 of 11 studies conducted in the real-world setting has summarized that, of the OACs (warfarin, dabigatran, rivaroxaban, and apixaban), apixaban is associated with the lowest risk for MB (apixaban vs warfarin hazard ratio [HR] ¼ 0.58; 95% confidence interval [CI] ¼ 0.48-0.69; apixaban vs dabigatran HR ¼ 0.73; 95% CI ¼ 0.61-0.87; apixaban vs rivaroxaban HR ¼ 0.55; 95% CI ¼ 0.46-0.66) 15 . Directionally consistent results in regard to bleeding outcomes have been reported in other meta-analyses of real-world data [16][17][18][19] .…”

“…Furthermore, depending on the DOAC investigated in the clinical trial, they were associated with lower or similar rates of bleeding relative to warfarin [6][7][8] . Other studies conducted in the real-world setting have more recently provided evidence that apixaban is associated with lower risks for stroke and major bleeding (MB) than warfarin, as well as lower risks for MB than rivaroxaban and dabigatran; although there is some variation in the results regarding the DOAC comparisons [9][10][11][12][13][14][15][16][17][18][19] . A network meta-analysis published in 2018 of 11 studies conducted in the real-world setting has summarized that, of the OACs (warfarin, dabigatran, rivaroxaban, and apixaban), apixaban is associated with the lowest risk for MB (apixaban vs warfarin hazard ratio [HR] ¼ 0.58; 95% confidence interval [CI] ¼ 0.48-0.69; apixaban vs dabigatran HR ¼ 0.73; 95% CI ¼ 0.61-0.87; apixaban vs rivaroxaban HR ¼ 0.55; 95% CI ¼ 0.46-0.66) 15 .…”

Ischaemic stroke and transient ischaemic attack on anticoagulants: outcomes in the era of direct oral anticoagulants

“…4 Plasma DOAC levels may aid decision making in the acute setting when thrombolysis is indicated. The majority of patients had mild stroke symptoms on presentation and discharge; however, 18% did not return home directly from acute care.…”

“…Apixaban was the most commonly used DOAC when a switch was made during the inpatient stay, possibly due to its perceived safety profile. 4 Plasma DOAC levels may aid decision making in the acute setting when thrombolysis is indicated. In acute ischaemic stroke, the benefit of thrombolysis is highly time-dependent but there are many barriers in obtaining the result quickly.…”