Thromboembolism in Heart Failure Patients in Sinus Rhythm: Epidemiology, Pathophysiology, Clinical Trials, and Future Direction.

Abstract Despite advances in medical and device therapy, patients with heart failure remain at high risk for morbidity and mortality. Experimental and clinical studies have shown an association between heart failure and a hypercoagulable state, and that patients with heart failure experience an increased incidence of stroke and other thromboembolic events, regardless of whether they are in atrial fibrillation. Although oral anticoagulation is recommended when atrial fibrillation is present, the benefits of this therapy in patients with heart failure in sinus rhythm are uncertain. Older randomized controlled trials comparing warfarin with antiplatelet therapy were, for the most part, underpowered and failed to show convincing benefits of warfarin therapy in this population. Several recent studies that assessed the effects of low-dose direct-acting oral anticoagulant therapy in patients with coronary artery disease in sinus rhythm either included or specifically targeted patients with heart failure. Post hoc analysis of their results showed that this treatment strategy was associated with improved outcomes in patients with acute coronary syndrome or stable coronary artery disease and also a significant reduction in thromboembolic events, including ischemic stroke. This review presents the rationale for anticoagulant therapy in patients with heart failure in sinus rhythm, discusses gaps in our knowledge base, offers suggestions for when anticoagulation might be considered, and identifies potential directions for future research.