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.
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).


CONCLUSIONS
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.
University of Birmingham Centre for Cardiovascular Sciences, City Hospital NHS Trust, Birmingham, B18 7QH, UK.|Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
Qinmei
Q
Xiong
University of Birmingham Centre for Cardiovascular Sciences, City Hospital NHS Trust, Birmingham, B18 7QH, UK.
Yee Cheng
YC
Lau
University of Birmingham Centre for Cardiovascular Sciences, City Hospital NHS Trust, Birmingham, B18 7QH, UK.
Keitaro
K
Senoo
University of Birmingham Centre for Cardiovascular Sciences, City Hospital NHS Trust, Birmingham, B18 7QH, UK.
Deirdre A
DA
Lane
Cardiovascular Department, the Second Affiliated Hospital of Nanchang University, Nanchang, China.
Kui
K
Hong
University of Birmingham Centre for Cardiovascular Sciences, City Hospital NHS Trust, Birmingham, B18 7QH, UK.|Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Gregory Y H
GY
Lip
D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D006333:Heart Failure / Q000150:complications*; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D020379:Risk Adjustment; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
D000925:Anticoagulants; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
Atrial fibrillation; Bleeding; Heart failure; Meta-analysis; NOAC; Stroke