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: 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). 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. 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). 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.