Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT.
Designing Future Clinical Trials in Heart Failure With Preserved Ejection Fraction: Lessons From TOPCAT.
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DOI：
10.1007/s11897-017-0336-x
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发表时间：
2017-08-01
影响因子：
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通讯作者：
Vaduganathan, Muthiah
中科院分区：
文献类型：
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作者：
Patel, Ravi B;Shah, Sanjiv J;Vaduganathan, Muthiah
目的回顾：在全球TOPCAT（使用醛固酮拮抗剂治疗保留心功能心力衰竭）试验中，对于保留射血分数（HFpEF）的慢性心力衰竭患者，螺内酯在主要复合终点方面没有表现出益处。我们从TOPCAT的经验中确定了可应用于未来HFpEF试验的关键教训。最近发现：TOPCAT的后续分析揭示了患者概况、事件发生率、药物依从性和治疗效果的显著区域异质性。显著的区域差异可能影响全球高强度pef试验的成功。考虑到TOPCAT美洲亚组的潜在益处，矿皮质激素受体拮抗剂可被考虑用于适当选择的HFpEF患者，以降低心力衰竭住院的风险。计划中的注册试验应提供关于螺内酯在HFpEF中的作用的额外证据。TOPCAT的整体设计、执行和研究监督为未来HFpEF试验的开展提供了关键的见解。
PURPOSE OF REVIEW: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials.RECENT FINDINGS: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects. Significant regional variation may impact the success of global HFpEF trials. Given potential benefits in the Americas subgroup in TOPCAT, mineralocorticoid receptor antagonists can be considered in appropriately selected patients with HFpEF to reduce risk of heart failure hospitalization. A planned registry-based trial should provide additional evidence regarding the role of spironolactone in HFpEF. The overall design, execution, and study oversight of TOPCAT have provided key insights into the conduct of future HFpEF trials.