BHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Lancet. 2024 Sep 21;404(10458):1119-1131. doi: 10.1016/S0140-6736(24)01733-1. Epub 2024 Sep 1.
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.
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.
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%).
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.
None.
醛固酮受体拮抗剂（MRA）可降低射血分数降低的心力衰竭（HFrEF）患者的住院率和死亡率，但在射血分数轻度降低的心力衰竭（HFmrEF）或射血分数保留的心力衰竭（HFpEF）患者中的获益尚不明确。我们评估了 MRA 在四项纳入射血分数不同的心力衰竭患者的试验中的作用。
这是一项对 RALES（螺内酯）和 EMPHASIS-HF（依普利酮）试验、纳入 HFrEF 患者的个体患者水平荟萃分析，以及 TOPCAT（螺内酯）和 FINEARTS-HF（非奈利酮）试验、纳入 HFmrEF 或 HFpEF 患者的个体患者水平荟萃分析。本荟萃分析的主要终点是首次心力衰竭或心血管死亡的复合终点。我们还估计了 MRA 对该复合终点的组成部分、全因（首次或重复）心力衰竭住院（伴或不伴心血管死亡）以及全因死亡率的影响。还评估了安全性结局，包括血清肌酐、估算肾小球滤过率、血清钾和收缩压。对试验和治疗之间的相互作用进行了检验，以检查这些人群中疗效的异质性。本研究在 PROSPERO 注册，注册号为 CRD42024541487。
四项试验共纳入 13846 名患者。MRA 降低了心血管死亡或心力衰竭住院的风险（风险比 0.77 [95%CI 0.72-0.83]）。由于 HFrEF 中的疗效更高（0.66 [0.59-0.73]），与 HFmrEF 或 HFpEF 相比（0.87 [0.79-0.95]），试验和治疗之间存在统计学显著的相互作用（p 交互=0.0012）。我们观察到心力衰竭住院率在 HFrEF 试验（0.63 [0.55-0.72]）和 HFmrEF 或 HFpEF 试验（0.82 [0.74-0.91]）中均显著降低。同样的模式也存在于伴有或不伴有心血管死亡的全因心力衰竭住院中。在 HFrEF 试验中，心血管死亡减少（0.72 [0.63-0.82]），但在 HFmrEF 或 HFpEF 试验中没有（0.92 [0.80-1.05]）。在 HFrEF 试验中，全因死亡率也降低（0.73 [0.65-0.83]），但在 HFmrEF 或 HFpEF 试验中没有（0.94 [0.85-1.03]）。与安慰剂相比，使用 MRA 会使高钾血症的风险增加一倍（比值比 2.27 [95%CI 2.02-2.56]），但严重高钾血症（血清钾>6.0mmol/L）的发生率较低（2.9%比 1.4%）；低钾血症（血清钾<3.5mmol/L）的风险减半（0.51 [0.45-0.57]；7%比 14%）。
甾体类 MRA 降低 HFrEF 患者的心血管死亡或心力衰竭住院风险，而非甾体类 MRA 降低 HFmrEF 或 HFpEF 患者的此类风险。
无。
