Heart failure and stroke: The underrepresentation of the heart failure with preserved ejection fraction subtype in randomized clinical trials of therapeutic anticoagulation

Heart failure (HF) is an important comorbidity for patients with ischemic stroke, present in 11 %–18 % of patients, and may also independently increase the risk of first-ever and recurrent ischemic stroke. HF is categorized based on ejection fraction (EF) into HF with reduced (HFrEF), mildly-reduced (HFmrEG) and preserved ejection fraction (HFpEF), with the efficacy of HF therapies differing between the three subcategories. Despite this classification, the incidence, recurrence rates and outcomes of ischemic stroke do not appear to differ significantly between the three subtypes, even when considering the concurrent presence of atrial fibrillation. However, several randomized-controlled clinical trials of anticoagulation defined HF based on reduced EF, inevitably excluding a large proportion of patients with HFpEF. This exclusion is significant considering marked differences between heart failure phenotypes. Such discrepancies raise concerns about the broad applicability of the results of these studies, including those of primary or secondary stroke prevention in HF. Future trials should include both patients with HFrEF and HFpEF to evaluate the safety and efficacy of antiocoagulation therapies in primary and secondary stroke prevention across the spectrum of the EF.