Optimization of Clinical Trial Design and Decision-Making for Heart Failure with Preserved Ejection Fraction (HFpEF): A Meta-Analysis Based on a Placebo Response Model

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2025-10-06 DOI:10.1155/cdr/7087720

Xiaoya Chen, Juan Yang, Ling Xu, Fang Yin, Jihan Huang, Yinghua Lv, Qingshan Zheng, Lujin Li

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引用次数: 0

Abstract

Objective

The aim of this study was to establish a placebo response model for efficacy indicators in heart failure with preserved ejection fraction (HFpEF) clinical trials, facilitating sample size estimation and trial optimization.

Methods

PubMed, EMBASE, and Cochrane Library databases were searched systematically for placebo-controlled trials of HFpEF up to May 26, 2024. Using model-based meta-analysis (MBMA), we analyzed cardiovascular death or heart failure hospitalization, cardiovascular death, heart failure hospitalization, all causes of death, and changes from baseline in the 6-min walk distance (6MWD) of the placebo group. The final model simulated the placebo effect distribution for these indicators under varying scenarios.

Results

A total of 29 studies and 14,302 participants were analyzed. A log-normal risk function was developed to describe four event rate indicators, and typical event rates for the placebo group over 6 years were simulated. After 1 year, rates for cardiovascular death or heart failure hospitalization (composite event), heart failure hospitalization, all causes of death, and cardiovascular death were 11.1%, 10.5%, 2.91%, and 2.33%, respectively. We used a linear model to describe the time–effect relationship of the change value of change from baseline in 6MWD, revealing typical changes at 1, 3, and 6 months as 1.47, 4.76, and 9.57 m, respectively. These values indicated that using the composite event as criteria could reduce the sample size by 500–12,000 cases, while 548 cases were sufficient for changes in 6MWD. The placebo effect model was also used as an external control in evaluating Sacubitril/Valsartan and exercise training efficacy.

Conclusion

This placebo response model provides essential support for sample size estimation, trial optimization, and drug efficacy evaluation in future HFpEF clinical trials.

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保留射血分数（HFpEF）心力衰竭临床试验设计和决策的优化：基于安慰剂反应模型的meta分析

目的建立心力衰竭保留射血分数（HFpEF）临床试验疗效指标的安慰剂反应模型，便于样本量估计和试验优化。方法系统检索PubMed、EMBASE和Cochrane Library数据库，检索截至2024年5月26日的HFpEF安慰剂对照试验。使用基于模型的meta分析（MBMA），我们分析了心血管死亡或心力衰竭住院、心血管死亡、心力衰竭住院、所有死亡原因，以及安慰剂组6分钟步行距离（6MWD）与基线的变化。最后的模型模拟了这些指标在不同情景下的安慰剂效应分布。结果共分析29项研究和14302名参与者。建立了一个对数正态风险函数来描述四个事件率指标，并模拟了安慰剂组6年以上的典型事件率。1年后，心血管死亡或心力衰竭住院率（复合事件）、心力衰竭住院率、所有死因死亡率和心血管死亡率分别为11.1%、10.5%、2.91%和2.33%。我们使用线性模型描述了6MWD中变化值与基线的时间效应关系，揭示了1、3和6个月的典型变化分别为1.47、4.76和9.57 m。这些值表明，使用复合事件作为标准可以将样本量减少500-12,000例，而548例足以反映6MWD的变化。同时采用安慰剂效应模型作为外部对照，评价苏比里尔/缬沙坦与运动训练的疗效。结论该安慰剂反应模型为今后HFpEF临床试验的样本量估计、试验优化和疗效评价提供了重要支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.