治疗心力衰竭的矿物质皮质激素受体拮抗剂:个体患者水平的荟萃分析。

IF 98.4 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
The Lancet Pub Date : 2024-09-21 Epub Date: 2024-09-01 DOI:10.1016/S0140-6736(24)01733-1
Pardeep S Jhund, Atefeh Talebi, Alasdair D Henderson, Brian L Claggett, Muthiah Vaduganathan, Akshay S Desai, Carolyn S P Lam, Bertram Pitt, Michele Senni, Sanjiv J Shah, Adriaan A Voors, Faiez Zannad, Scott D Solomon, John J V McMurray
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引用次数: 0

摘要

背景:矿物皮质激素受体拮抗剂(MRAs)可减少射血分数降低型心力衰竭(HFrEF)患者的住院和死亡,但对射血分数轻度降低型心力衰竭(HFmrEF)或射血分数保留型心力衰竭(HFpEF)患者的益处尚不清楚。我们在四项试验中评估了 MRA 的效果,这些试验招募了不同射血分数的心衰患者:这是一项预先指定的、个体患者水平的荟萃分析,研究对象包括RALES(螺内酯)和EMPHASIS-HF(依普利酮)试验(这两项试验均招募了HFrEF患者),以及TOPCAT(螺内酯)和FINEARTS-HF(非那列酮)试验(这两项试验均招募了HFmrEF或HFpEF患者)。这项荟萃分析的主要结果是心衰首次住院或心血管死亡的复合时间。我们还估算了 MRA 对这一复合结果的影响、心衰住院总次数(首次或重复)(有心血管死亡或无心血管死亡)以及全因死亡的影响。此外还评估了安全性结果,包括血清肌酐、估计肾小球滤过率、血清钾和收缩压。测试了试验与治疗之间的交互作用,以检验这些人群中的异质性效应。本研究已在 PROSPERO 注册,编号为 CRD42024541487:四项试验共纳入 13 846 名患者。MRA降低了心血管死亡或心衰住院的风险(危险比为0-77 [95% CI 0-72-0-83])。与 HFmrEF 或 HFpEF(0-87 [0-79-0-95])相比,MRAs 对 HFrEF(0-66 [0-59-0-73])的疗效更高,因此试验与治疗之间存在统计学意义上的交互作用(交互作用 p=0-0012)。我们观察到,在 HFrEF 试验(0-63 [0-55-0-72] )和 HFmrEF 或 HFpEF 试验(0-82 [0-74-0-91] )中,心衰住院率明显降低。在有或无心血管死亡的心衰住院总人数中也观察到了同样的模式。HFrEF试验(0-72 [0-63-0-82])减少了心血管死亡,但HFmrEF或HFpEF试验(0-92 [0-80-1-05])没有减少心血管死亡。HFrEF 试验(0-73 [0-65-0-83])也降低了全因死亡风险,但 HFmrEF 或 HFpEF 试验(0-94 [0-85-1-03])并未降低全因死亡风险。与安慰剂相比,使用 MRA 时发生高钾血症的风险增加了一倍(几率比 2-27 [95% CI 2-02-2-56]),但严重高钾血症(血清钾 >6-0 mmol/L)的发生率较低(2-9% vs 1-4%);低钾血症(血钾 解读:类固醇 MRA 可降低高钾血症(血清钾 >6-0 mmol/L)的风险:类固醇 MRAs 可降低 HFrEF 患者心血管死亡或心衰住院的风险,而非类固醇 MRAs 可降低 HFmrEF 或 HFpEF 患者的这一风险:无。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis.

Background: Mineralocorticoid receptor antagonists (MRAs) reduce hospitalisations and death in patients with heart failure and reduced ejection fraction (HFrEF), but the benefit in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF) is unclear. We evaluated the effect of MRAs in four trials that enrolled patients with heart failure across the range of ejection fraction.

Methods: This is a prespecified, individual patient level meta-analysis of the RALES (spironolactone) and EMPHASIS-HF (eplerenone) trials, which enrolled patients with HFrEF, and of the TOPCAT (spironolactone) and FINEARTS-HF (finerenone) trials, which enrolled patients with HFmrEF or HFpEF. The primary outcome of this meta-analysis was a composite of time to first hospitalisation for heart failure or cardiovascular death. We also estimated the effect of MRAs on components of this composite, total (first or repeat) heart failure hospitalisations (with and without cardiovascular deaths), and all-cause death. Safety outcomes were also assessed, including serum creatinine, estimated glomerular filtration rate, serum potassium, and systolic blood pressure. An interaction between trials and treatment was tested to examine the heterogeneity of effect in these populations. This study is registered with PROSPERO, CRD42024541487.

Findings: 13 846 patients were included in the four trials. MRAs reduced the risk of cardiovascular death or heart failure hospitalisation (hazard ratio 0·77 [95% CI 0·72-0·83]). There was a statistically significant interaction by trials and treatment (p for interaction=0·0012) due to the greater efficacy in HFrEF (0·66 [0·59-0·73]) compared with HFmrEF or HFpEF (0·87 [0·79-0·95]). We observed significant reductions in heart failure hospitalisation in the HFrEF trials (0·63 [0·55-0·72]) and the HFmrEF or HFpEF trials (0·82 [0·74-0·91]). The same pattern was observed for total heart failure hospitalisations with or without cardiovascular death. Cardiovascular death was reduced in the HFrEF trials (0·72 [0·63-0·82]) but not in the HFmrEF or HFpEF trials (0·92 [0·80-1·05]). All-cause death was also reduced in the HFrEF trials (0·73 [0·65-0·83]) but not in the HFmrEF or HFpEF trials (0·94 [0·85-1·03]). With an MRA, the risk of hyperkalaemia was doubled compared with placebo (odds ratio 2·27 [95% CI 2·02-2·56]), but the incidence of serious hyperkalaemia (serum potassium >6·0 mmol/L) was low (2·9% vs 1·4%); the risk of hypokalaemia (potassium <3·5 mmol/L) was halved (0·51 [0·45-0·57]; 7% vs 14%).

Interpretation: Steroidal MRAs reduce the risk of cardiovascular death or heart failure hospitalisation in patients with HFrEF and non-steroidal MRAs reduce this risk in patients with HFmrEF or HFpEF.

Funding: None.

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来源期刊
The Lancet
The Lancet 医学-医学:内科
CiteScore
148.10
自引率
0.70%
发文量
2220
审稿时长
3 months
期刊介绍: The Lancet is a world-leading source of clinical, public health, and global health knowledge. It was founded in 1823 by Thomas Wakley and has been an independent, international weekly general medical journal since then. The journal has an Impact Factor of 168.9, ranking first among 167 general and internal medicine journals globally. It also has a Scopus CiteScore of 133·2, ranking it second among 830 general medicine journals. The Lancet's mission is to make science widely available to serve and transform society, positively impacting people's lives. Throughout its history, The Lancet has been dedicated to addressing urgent topics, initiating debate, providing context for scientific research, and influencing decision makers worldwide.
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