Non-vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with heart failure and preserved, mildly reduced, and reduced ejection fraction: A systemic review and meta-analysis

Abstract

BackgroundPatient prevalence of atrial fibrillation (AF) and heart failure (HF) is increasing, and anticoagulation for patients from heterogeneous backgrounds with both conditions remains controversial. In this meta-analysis, we are aiming to compare the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in AF patients with HF and preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction.Methods and resultsWe systematically searched the PubMed, Cochrane, and Embase databases until January 2022. The primary effectiveness and safety outcomes were stroke or systemic embolism (SSE) and major bleeding, respectively. We abstracted risk ratios (RR) and 95% confidence intervals (CIs) and compiled them using a random-effects model. We analyzed data of 266,291 patients from 10 studies. By comparing NOACs with warfarin, patients with AF and HF have reduced the risk of SSE (RR: 0.83, 95% CI 0.76–0.91), all-cause mortality (RR: 0.85, 95% CI 0.80–0.91), major bleeding (RR: 0.79, 95% CI 0.69–0.90), and intracranial hemorrhage (RR: 0.54, 95% CI 0.46–0.63). Further analyses based on the HF subtypes showed that NOACs reduced the chances of SSE (RR: 0.71, 95% CI 0.53–0.94) in the HFrEF group and major bleeding (RR: 0.74, 95% CI 0.57–0.95) in HFmrEF and HFpEF groups. There were no differences regarding SSE (RR: 0.91, 95% CI 0.76–1.09) in HFmrEF and HFpEF groups and major bleeding (RR: 0.99, 95% CI 0.79–1.23) in the HFrEF group.ConclusionFor patients with AF and HF, NOACs have better or similar effectiveness and safety than warfarin, but the stroke prevention superiority of NOACs over warfarin varies in different HF subtypes.

Clinical outcomes and anticoagulation therapy in elderly non‐valvular atrial fibrillation and heart failure patients

“…Thus, although detailed echocardiographic data were not available in this subanalysis, most patients with HF in this study may have HFpEF or HF with mildly reduced ejection fraction (HFmrEF). A previous meta‐analysis including 10 studies showed that DOAC use was associated with lower risks for stroke or systemic embolism and major bleeding in patients with AF and HFpEF or HFmrEF 34 . Our subanalysis presents similar results to this meta‐analysis in elderly patients; however, further study may be required to elucidate the effectiveness of DOAC use in older patients with AF and HFrEF.…”

“…A previous meta-analysis including 10 studies showed that DOAC use was associated with lower risks for stroke or systemic embolism and major bleeding in patients with AF and HFpEF or HFmrEF. 34 Our subanalysis presents similar results to this meta-analysis in elderly patients; however, further study may be required to elucidate the effectiveness of DOAC use in older patients with AF and HFrEF. Third, recently emerging drugs such as angiotensin receptor-neprilysin inhibitor (ARNI) and sodiumglucose cotransporter-2 (SGLT-2) inhibitors were not used when the ANAFIE Registry was performed, 35,36 although apparent interaction has not been reported between SGLT-2 inhibitors or ARNI and OAC therapy.…”

Association of hypertension burden with stroke risk in patients with heart failure with preserved ejection fraction

“…In the review performed by Shantsila et al, OAC was a non-superior lowering-stroke option for HFpEF patients with sinus rhythm, with no information regarding the antithrombotic effects of OAC versus antiplatelets [ 10 ]. Non-vitamin K oral anticoagulant (NOAC) was a novel marketed anticoagulant for better safety outcomes but had no significant difference in systemic embolism risk among HFpEF patients with AF [ 26 ]. Due to the HFpEF heterogeneity and AF history, the efficacy of OAC for stroke reduction in HFpEF patients was still controversial, and hence more data regarding OAC therapy would be provided in future studies.…”