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Stroke in Heart Failure With Reduced Ejection Fraction: Systematic Review and Meta-Analysis of Randomized Trials
Guglielmo Gallone1, Federica Savoca1, Davide Miccoli1
1Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy; Department of Medical Sciences, University of Turin, Italy.
JACC. Heart Failure
|March 15, 2025
Summary
Stroke is a significant risk in heart failure with reduced ejection fraction (HFrEF), yet under-reported in trials. This meta-analysis found a 1.1% stroke incidence, associated with mortality and hospitalizations, but unaffected by current HFrEF treatments.
Area of Science:
- Cardiology
- Neurology
- Clinical Trials
Background:
- Heart failure with reduced ejection fraction (HFrEF) is linked to increased stroke risk.
- Stroke outcomes are frequently under-reported in clinical trials for HFrEF.
Purpose of the Study:
- To determine the incidence, characteristics, predictors, and prognostic impact of stroke in patients with HFrEF.
- To analyze the influence of treatments on stroke events within HFrEF randomized controlled trials (RCTs).
Main Methods:
- Systematic review of MEDLINE for RCTs involving HFrEF treatments.
- Meta-analysis of stroke incidence from 30 eligible RCTs (75,327 patients).
- Subgroup analyses and meta-regressions to identify stroke predictors and treatment associations.
Main Results:
- Stroke incidence was 1.1% (95% CI: 0.9%-1.3%) across 30 RCTs, with significant heterogeneity.
- Higher NYHA class, lower systolic blood pressure, diuretic use, and diabetes were associated with stroke.
- Stroke correlated with increased all-cause mortality, cardiovascular mortality, heart failure hospitalizations, and acute coronary syndromes.
Conclusions:
- Stroke is under-reported in HFrEF RCTs, with heterogeneous definitions and unclear mechanisms.
- Despite under-reporting, stroke incidence is substantial and linked to HFrEF characteristics and adverse outcomes.
- Current HFrEF therapies do not appear to impact stroke incidence, highlighting a need for dedicated research into prevention and treatment strategies.