Novel Oral Anticoagulants in AF and Heart Failure

Study Questions:

What is the safety and efficacy of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF)?


The authors performed a meta-analysis of four phase III clinical trials comparing NOACs to warfarin in patients with AF. HF was defined according to individual trial definitions. Prespecified outcomes included the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular and all-cause death among NOAC-treated patients with and without HF.


Of 55,011 patients enrolled in the four trials, 26,384 (48%) had a diagnosis of HF. Median age was 70 years, with 36% female and a follow-up of 1.5-2.8 years. There were similar rates of SSE (1.74 vs. 1.67%/year; RR, 0.98; 95% CI, 0.90-1.07) and major bleeding (2.70 vs. 3.02%/patient-year; RR, 0.95; 95% CI, 0.88-1.03) for HR versus no-HF patients, respectively. HF patients had reduced rates of total bleeding (11.80 vs. 15.62%/patient-year; RR, 0.86; 95% CI, 0.81-0.91) and intracranial bleeding (0.45 vs. 0.60%/patient-year; RR, 0.74; 95% CI, 0.63-0.88), but higher rates of all-cause death (5.21 vs. 3.20%/patient-year; RR, 1.70; 95% CI, 1.31-2.19) and cardiovascular death (3.62 vs. 1.84%/patient-year; RR, 2.05; 95% CI, 1.66-2.55) as compared to non-HF patients treated with NOACs. Compared with warfarin, NOACs significantly reduced SSE and bleeding (SSE, major, intracranial, and total) regardless of the presence or absence of HF (p value for interaction > 0.05 for each).


The authors concluded that patients with AF and HF experience increased mortality, but have reduced rates of intracranial and total bleeding as compared to non-HF patients with AF. They also concluded that NOACs significantly reduced SSE, major bleeding, and intracranial bleeding in HF patients.


AF and HF are highly comorbid illnesses and place patients at increased risk of stroke and mortality. This meta-analysis, which includes all four phase III clinical trials of NOACs versus warfarin for stroke prevention in AF, confirms that the major findings in the general AF population hold true for the HF population—namely that NOACs, as a class, reduce the risk of SSE, major bleeding, and (most impressively) intracranial bleeding. It is not surprising that AF patients with HF experience higher mortality rates than non-HF patients with AF, and this finding does not appear to be affected by the choice of oral anticoagulant. While this meta-analysis did not include individual patient-level data, it is still reassuring that the overall findings of the NOAC versus warfarin trials can apply to the large population of patients with comorbid AF and HF.

Keywords: Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Embolism, Geriatrics, Heart Failure, Hemorrhage, Intracranial Hemorrhages, Primary Prevention, Stroke, Vascular Diseases, Warfarin

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