Relative efficacy and safety of non-Vitamin K oral anticoagulants for non-valvular atrial fibrillation: Network meta-analysis comparing apixaban, dabigatran, rivaroxaban and edoxaban in three patient subgroups.

BACKGROUND: Stroke is the most serious clinical consequence of atrial fibrillation, which is the most common cardiac arrhythmia. Non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as efficacious, safe and convenient stroke prevention agents. This updated network meta-analysis focused on the relative efficacy and safety of apixaban compared with dabigatran, rivaroxaban and edoxaban for stroke prevention in (i) patients with CHADS2 score ≥ 2, (ii) secondary stroke prevention, and (iii) patients with high quality anticoagulation control with warfarin. METHODS AND RESULTS: A fixed-effects network meta-analysis was conducted, including data from four Phase III randomised controlled trials (> 70,000 patients with non-valvular atrial fibrillation). The results of the base-case analysis comparing NOACs with warfarin were broadly in line with the results from the individual trials. Results from the three subgroup analyses were broadly similar to the base case results. For example in patients with CHADS2 score ≥ 2, apixaban, high-dose dabigatran, rivaroxaban, and high-dose edoxaban had significantly lower hazards of stroke/systemic embolism compared with low-dose edoxaban. Apixaban and low-dose edoxaban were associated with significantly lower hazards of major bleeding compared with rivaroxaban and dabigatran 150 mg. However, several treatment comparisons that were significant in the base-case analysis were not significant in the patient subgroups, due to the reduced sample size of the subgroups compared with the overall population. CONCLUSIONS: Among the NOACs, apixaban offered the most favourable efficacy and safety profile in the overall patient population as well as in the three subgroups investigated.

Stroke associated with discontinuation of warfarin therapy for atrial fibrillation.

OBJECTIVE: The objective of this study was to determine the association between warfarin discontinuation and stroke among patients with nonvalvular atrial fibrillation (NVAF). RESEARCH DESIGN AND METHODS: This was a retrospective, observational study of adult NVAF patients (≥ 18 years) who were on warfarin in the Truven MarketScan commercial claims and encounters and Medicare supplemental and coordination of benefits databases (1 January 2008 to 30 June 2012). Warfarin discontinuation was defined as a gap of ≥ 45 days in warfarin prescription within 1 year after initiation. Patients who did and did not discontinue warfarin were matched at a 1:1 ratio using a propensity score method. Matched patients were followed for up to 1 year to determine risks of ischemic stroke, transient ischemic attack (TIA), and hemorrhagic stroke. A multivariate Cox proportional hazards model was used to further adjust for the effects of potential confounders. RESULTS: A total of 27,000 patients were included. Patients who discontinued warfarin had higher rates of ischemic stroke compared to persistent patients (1.0 vs. 0.5 per 100 patient years, P < 0.01), but similar rates of TIA (1.2 vs. 0.9 per 100 patient years, respectively; P = 0.07) and hemorrhagic stroke (0.3 vs. 0.2 per 100 patient years, P = 0.31). After adjustment for potential confounders, warfarin discontinuation was significantly associated with increased risk of ischemic stroke (hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.47-2.84), TIA (HR: 1.36; 95% CI: 1.04-1.78), and ischemic stroke or TIA (HR: 1.50; 95% CI: 1.20-1.87). CONCLUSIONS: Warfarin discontinuation is associated with increased risk of ischemic stroke and TIA. Health care providers may need to take a more active role in the management of warfarin discontinuation and clinical outcomes, e.g., by considering newer anticoagulants with favorable risk-benefit profiles. Key limitations of the study include unavailability of important clinical factors and measures in claims data.