Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study

Background Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. Objectives This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013‐30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score‐matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. Results Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55–0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72–0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57–0.66) and dabigatran (HR: 0.79, 95% CI: 0.70–0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08–1.21) was associated with a higher risk vs warfarin. Conclusion Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real‐world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population

Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study

Background Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. Objectives This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013‐30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score‐matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. Results Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55–0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72–0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57–0.66) and dabigatran (HR: 0.79, 95% CI: 0.70–0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08–1.21) was associated with a higher risk vs warfarin. Conclusion Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real‐world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population

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

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.Published versio