Rationale and design of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial: A randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction
Rationale and design of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial: A randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction
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DOI：
10.1016/j.ahj.2011.09.007
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发表时间：
2011-12-01
影响因子：
4.8
通讯作者：
Pfeffer, Marc A.
中科院分区：
文献类型：
--
作者：
Desai, Akshay S.;Lewis, Eldrin F.;Pfeffer, Marc A.
背景尽管射血分数保留（PEF）患者的心力衰竭（HF）患病率不断增加，但目前尚无有效的治疗方法证明可降低发病率和死亡率。醛固酮是一种强有力的心肌和血管纤维化刺激因子，可能是该人群HF进展的关键介质，因此是一个重要的治疗靶点。目的TOPCAT试验旨在评估醛固酮拮抗剂螺内酯对HF PEF患者发病率、死亡率和生活质量的影响。515例HF-PEF患者将以双盲方式随机接受螺内酯（目标剂量30 mg/天）或匹配安慰剂治疗。符合条件的患者包括年龄≥ 50岁，左心室射血分数≥ 45%，有症状的HF，以及在前一年内因HF住院或在随机化前60天内钠尿肽水平升高（B型钠尿肽≥ 100 pg/mL或N-末端B型钠尿肽前体≥ 360 pg/mL）。不受控制的高血压患者和已知的浸润性或肥厚性心肌病患者被排除在外。主要终点是心血管死亡、因HF住院或心脏骤停流产的复合终点。关键次要终点包括生活质量、非致死性心血管事件和新发房颤。辅助研究的超声心动图，眼压测量，心脏生物标志物将提供更多的洞察力，这understudied人口和螺内酯therapeutic.Conclusion TOPCAT的目的是明确评估的作用，螺内酯在管理HF-PEF。(Am Heart J 2011;162：966-972.e10.）
Background Despite increasing prevalence of heart failure (HF) in patients with preserved ejection fraction (PEF), there are no available therapies proven to reduce morbidity and mortality. Aldosterone, a potent stimulator of myocardial and vascular fibrosis, may be a key mediator of HF progression in this population and is therefore an important therapeutic target.Objective The TOPCAT trial is designed to evaluate the effect of spironolactone, an aldosterone antagonist, on morbidity, mortality, and quality of life in patients with HF-PEF.Methods Up to 3,515 patients with HF-PEF will be randomized in double-blind fashion to treatment with spironolactone (target dose 30 mg daily) or matching placebo. Eligible patients include those with age >= 50 years, left ventricular ejection fraction >= 45%, symptomatic HF, and either a hospitalization for HF within the prior year or an elevated natriuretic peptide level (B-type natriuretic peptide >= 100 pg/mL or N-terminal pro-B-type natriuretic peptide >= 360 pg/mL) within the 60 days before randomization. Patients with uncontrolled hypertension and those with known infiltrative or hypertrophic cardiomyopathy are excluded. The primary end point is the composite of cardiovascular death, hospitalization for HF, or aborted cardiac arrest. Key secondary end points include quality of life, nonfatal cardiovascular events, and new-onset atrial fibrillation. Ancillary studies of echocardiography, tonometry, and cardiac biomarkers will provide more insight regarding this understudied population and the effects of spironolactone therapy.Conclusion TOPCAT is designed to assess definitively the role of spironolactone in the management of HF-PEF. (Am Heart J 2011;162:966-972.e10.)