Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure: a systemic review and meta-analysis of randomized trials

Abstract

Background: No pooled analysis has been undertaken to assess the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized controlled trials (RCTs).

Methods: Comprehensive literature searches were conducted using the Cochrane Library, MEDLINE, and Scopus databases from inception to April 2015. Statistical analyses were performed using RevMan 5.3 software.

Results: Four RCTs were included: 19 122 of 32 512 AF patients with HF were allocated to a NOAC (13 384 receiving single-/high-dose NOAC regimens), and 13 390 to warfarin. Among AF patients with HF, single/high-dose NOACs significantly reduced the risk of stroke/systemic embolic (SE) events by 14% [odds ratio0.86, 95% confidence interval (CI) 0.76-0.98), and had a 24% lower risk of major bleeding(OR 0.76, 95% CI 0.67-0.86). For low-dose NOAC regimens, comparable efficacy to warfarin for stroke or SE events (OR 1.02, 95% CI 0.86-1.21) and a non-significant trend for lower major bleeding was observed. Regardless of high- or low-dose NOAC, the incidences of both major bleeding and stroke/SE in AF patients with HF were similar to those without HF. Atrial fibrillation patients with HF on NOACs had a 41% lower risk of intracranial haemorrhage compared with those without HF (OR 0.59, 95% CI 0.40-0.87).

Conclusion: Among AF patients with HF, single-/high-dose NOAC regimens have a better efficacy and safety profile, but low-dose regimens had similar efficacy and safety to warfarin. NOACs were similarly effective or even safer (less intracranial haemorrhage) in AF patients with HF compared with those without HF.

Keywords: Atrial fibrillation; Bleeding; Heart failure; Meta-analysis; NOAC; Stroke.