Stroke in Heart Failure With Reduced Ejection Fraction

IF 10.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure Pub Date : 2025-07-01 DOI:10.1016/j.jchf.2024.12.008

Guglielmo Gallone MD , Federica Savoca MD , Davide Miccoli MD , Michael Böhm MD, PhD , Gaetano Maria De Ferrari MD , Stephen S. Gottlieb MD , Patrizio Lancellotti MD, PhD , JoAnn Lindenfeld MD , Clara Saldarriaga MD , Zainab Samad MBBS , John R. Teerlink MD , Gianluigi Savarese MD, PhD , Enrico Ammirati MD, PhD

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Abstract

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)

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心力衰竭卒中伴射血分数降低：随机试验的系统评价和荟萃分析。

背景：心力衰竭伴射血分数降低（HFrEF）的患者卒中风险增高。然而，中风作为心力衰竭试验终点的报道仍然很少。目的：作者试图确定纳入随机对照试验（RCTs）的HFrEF患者卒中的发生率、特征、预测因素、改良治疗和预后影响。方法：作者系统地回顾MEDLINE关于HFrEF的药物和非药物治疗的随机对照试验。年化脑卒中发生率是主要观察指标。进行亚组分析和meta回归，以确定基线调节特征，并评估卒中与其他临床结果的关联。结果：7104条记录中，188项rct符合系统评价的纳入标准。其中，158项研究（84.0%）未报告卒中结局，因此被排除在meta分析之外，最终纳入了30项研究，共61组，75,327例患者。卒中发生率为1.1% (95% CI: 0.9%-1.3%；I2: 74%)，各试验间异质性高。较高的NYHA功能等级（P < 0.001）、较低的收缩压（P < 0.001）、利尿剂使用（P = 0.001）和糖尿病（P < 0.001）与卒中相关。未观察到肾素-血管紧张素-醛固酮抑制剂、受体阻滞剂、矿皮质激素受体拮抗剂和经导管二尖瓣置换术与卒中的相关性。卒中与全因死亡率、心血管死亡率、心力衰竭住院率和急性冠状动脉综合征的高风险相关（P < 0.001）。结论：在绝大多数HFrEF随机对照试验中，卒中的定义不一致，且未提及其潜在机制。尽管报告不足，但中风的发病率是不可忽视的。卒中与HFrEF特异性特征和结果相关，而目前的HFrEF治疗不影响卒中。有必要专门研究预防战略和有效治疗方法，以解决这种使人衰弱和致命的合并症。心力衰竭伴射血分数降低的卒中事件——药物随机试验的系统回顾和荟萃分析；CRD42023418422)。

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来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.