Objectives

The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.

Background

Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics.

Methods

TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m² and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years).

Results

The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region.

Conclusions

In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302)

中文翻译：

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年龄对螺内酯治疗心力衰竭的疗效和安全性的影响。

目标

作者检查了螺环内酯在美国地区（N = 1,767）的年龄（TOPCAT（醛固酮拮抗剂治疗保留的心脏功能性心力衰竭））的疗效和安全性。

背景

保留射血分数的心力衰竭会不成比例地影响老年人，这些老年人可能表现出生理学变化和药代动力学变化。

方法

TOPCAT纳入了心力衰竭且左心室射血分数≥45％的患者，年龄在50岁或以上，估计肾小球滤过率≥30mL / min / 1.73 m ^2，并且先前曾因心力衰竭住院或钠尿肽水平升高。参与者被随机分为螺内酯或安慰剂，平均随访时间为3.3年。我们通过协议定义的年龄类别（<65岁，65岁至74岁和≥75岁）评估了治疗效果和安全性。

结果

平均年龄为72±10岁（范围为50到97岁），其中75岁以上的年龄为41％。≥75岁的参与者较常见于女性和白人，与较年轻的年龄类别相比，其体重指数和估计的肾小球滤过率较低。与安慰剂相比，螺环内酯在所有年龄段的患者中均降低了主要的复合终点（p交互作用= 0.42）。然而，螺内酯与安全终点的风险增加相关（危险比：2.54； 95％置信区间：1.91至3.37； p <0.001），尤其是在老年组中（p交互作用= 0.02）。整个TOPCAT队列的结果与美洲地区的结果一致。

结论

在此之后，对美洲地区的TOPCAT试验数据进行了探索性分析，尽管年龄对疗效没有影响，但年龄对不良安全后果增加的比率有相当大的影响。当考虑使用螺内酯治疗射血分数保留的老年心力衰竭时，应权衡这些结果。（用醛固酮拮抗剂治疗保留的心功能性心力衰竭[TOPCAT]； NCT00094302）