beta-blockers; heart failure with reduced ejection fraction; mineralocorticoid-receptor antagonists; randomized controlled trial; renin-angiotensin-aldosterone inhibitors; stroke; Cardiology and Cardiovascular Medicine
Abstract :
[en] [en] BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) have a heightened stroke risk. However, stroke as an endpoint in heart failure trials remains under-reported.
OBJECTIVES: The authors sought to define the incidence, characteristics, predictors, modifier treatments, and prognostic impact of stroke in patients with HFrEF who were enrolled in randomized controlled trials (RCTs).
METHODS: The authors systematically reviewed MEDLINE for RCTs of pharmacologic and nonpharmacologic treatments in HFrEF. The annualized stroke incidence was the primary outcome. Subgroup analyses and meta-regressions were performed to determine the baseline modulating characteristics and to assess the association of stroke with other clinical outcomes.
RESULTS: Of 7,104 records, 188 RCTs fulfilled inclusion criteria for the systematic review. Of these, 158 studies (84.0%) did not report stroke outcomes and were excluded from the meta-analysis, leading to a final cohort of 30 studies, with 61 arms and 75,327 patients. Stroke incidence was 1.1% (95% CI: 0.9%-1.3%; I2: 74%) with high heterogeneity across trials. Higher NYHA functional class (P < 0.001), lower systolic blood pressure (P < 0.001), diuretic use (P = 0.001), and diabetes (P < 0.001) were associated with stroke. No association of renin-angiotensin-aldosterone inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and transcatheter mitral valve replacement with stroke was observed. Stroke was associated with higher risk of all-cause and cardiovascular mortality, heart failure hospitalization and acute coronary syndromes (P < 0.001 for all).
CONCLUSIONS: Stroke was reported in a vast minority of HFrEF RCTs with heterogeneous definitions and no reference to underlying mechanisms. Despite under-reporting, stroke incidence is non-negligible. Stroke is associated with HFrEF-specific characteristics and outcomes, whereas it is not impacted by current HFrEF treatments. There is a need for dedicated research into preventive strategies and effective treatments to address this debilitating and deadly comorbidity. (Stroke Events in Heart Failure With Reduced Ejection Fraction-A Systematic Review and Meta-Analysis of Pharmacologic Randomized Trial; CRD42023418422).
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Gallone, Guglielmo; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy. Electronic address: guglielmo.gallone@gmail.com
Savoca, Federica; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Miccoli, Davide; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Böhm, Michael; Clinic III for Internal Medicine (Cardiology, Angiology, and Intensive Care Medicine) Saarland University, Homburg/Saar, Germany
De Ferrari, Gaetano Maria ; Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza, Turin, Italy, Department of Medical Sciences, University of Turin, Italy
Gottlieb, Stephen S; Division of Cardiovascular Medicine, University of Maryland School of Medicine and Baltimore, Veterans Administration Medical Center, Baltimore, Maryland, USA
Lancellotti, Patrizio ; Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation
Lindenfeld, JoAnn; Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Saldarriaga, Clara; CardioVID Clinic, University of Antioquia, Medellín, Colombia
Samad, Zainab ; The Aga Khan University, Karachi, Pakistan
Teerlink, John R; Section of Cardiology, San Francisco Veterans Affairs Medical Center, School of Medicine, University of California San Francisco, San Francisco, California, USA
Savarese, Gianluigi ; Department of Clinical Science, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
Ammirati, Enrico ; De Gasperis Cardio Center, Transplant Center, Niguarda Hospital, Milano, Italy, Department of Health Sciences, University of Milano-Bicocca, Monza, Italy
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