AimHeart failure (HF) is a prothrombotic state, but current evidence does not support the routine use of aspirin, antiplatelet agents, or anticoagulation in these patients in sinus rhythm (SR). We conducted an updated meta-analysis comparing these medications on outcomes in HF.Methods and resultsAll randomized trials in patients with chronic HF and reduced ejection fraction (HFREF) in sinus rhythm (SR; n>100), in which the effect of aspirin, antiplatelet agents, or anticoagulants was determined, were prospectively evaluated. Four trials met the entry criteria. Intervention time was 28 months. No difference in all-cause mortality was seen when aspirin was compared with warfarin [n = 3701, relative risk (RR) 1.00, 95 confidence interval (CI) 0.88-1.13, P = 0.94]. Compared with aspirin, significantly fewer strokes were seen with warfarin (n = 3701, RR 0.59, 95 CI 0.41-0.85, P = 0.004), and fewer fatal and non-fatal ischaemic strokes (n = 3368, RR 0.48, 95 CI 0.32-0.73, P = 0.0006). Warfarin doubled the risk of major haemorrhage compared with aspirin (n = 3701, RR 2.02, 95 CI 1.45-2.80, P <0.0001); however, intracranial haemorrhage was rare. There was no significant difference in HF hospitalizations with aspirin vs. warfarin (n = 3701, RR 1.16, 95 CI 0.79-1.71, P = 0.45).ConclusionWith warfarin compared with aspirin in HFREF in SR, significant reductions in stroke risk were observed but no mortality benefit was seen. Major haemorrhage doubled but intracranial haemorrhage was rare. These findings suggest that overall the benefit of warfarin in HFREF in SR outweighs the risk. Aspirin use did not increase HF hospitalization as has been previously suggested.