This systematic review aims to evaluate the comparative effectiveness and safety of anticoagulation versus other lines of antithrombotic therapies in preventing recurrent stroke in Heart Failure (HF) patients in Sinus Rhythm (SR). 

Recurrent ischemic stroke (RIS) is a significant clinical concern in patients with Heart Failure (HF), particularly those in Sinus Rhythm (SR), a population in whom optimal strategies for secondary stroke prevention remain unclear.

We conducted a systematic search of PubMed, Scopus, and Web of Science (June 2025). Studies included adult Heart Failure patients in Sinus Rhythm with a prior ischemic stroke and compared oral anticoagulants to antiplatelet therapy or no treatment. The primary outcome was RIS and secondary outcomes included major bleeding and all-cause mortality.

Five studies (3 RCTs, 2 cohorts) met inclusion criteria. Evidence was primarily derived from subgroup or post-hoc analyses. Anticoagulation demonstrated potential benefit in select subgroups (e.g., left ventricular dysfunction), but overall evidence was inconsistent. Anticoagulants were associated with increased bleeding risk in all studies, and no reduction in mortality was observed.

Secondary stroke prevention in HF patients in Normal Sinus Rhythm remains significantly understudied. While certain subgroups may derive benefit, the elevated bleeding risk and lack of mortality improvement highlight the need for caution. Large, well-designed trials are needed to clarify patient subgroups that might benefit from anticoagulation in this setting.