1st Cardiology Clinic, National and Kapodistrian University of Athens, School of Medicine, Hippokration General Hospital, Athens, Greece; Department of Hygiene, Social-Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece.
Department of Hygiene, Social-Preventive Medicine & Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, University Campus, 54124 Thessaloniki, Greece; Second Cardiology Department, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Curr Probl Cardiol. 2024 Jul;49(7):102615. doi: 10.1016/j.cpcardiol.2024.102615. Epub 2024 Apr 29.
Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF.
MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE).
Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]).
MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.
几项随机对照试验（RCT）已经研究了在射血分数降低的心力衰竭（HFrEF）中使用盐皮质激素受体拮抗剂（MRA）。本系统评价和网络荟萃分析（NMA）评估了 MRA 在 HFrEF 中的比较疗效和安全性。
直到 2024 年 4 月 8 日，我们在 MEDLINE（PubMed）、Scopus、Cochrane 和 ClinicalTrials.gov 上搜索了研究 MRA 在 HFrEF 中的疗效和/或安全性的 RCT。进行了双重独立的研究选择、提取和质量评估。使用随机效应似然比 NMA 模型。通过评估、制定和评估（GRADE）评估证据确定性。
总共分析了 32 项 RCT（15685 名患者）。依普利酮在全因死亡率（风险比{HR}=0.78，95%置信区间{CI}[0.66，0.91]，GRADE：“中度”）、心血管死亡（HR=0.74，95%CI[0.53，1.04]，GRADE：“低”）和所有安全性结局方面均优于螺内酯。螺内酯在心血管死亡或住院的复合结局（HR=0.67，95%CI[0.50，0.89]，GRADE：“中度”）、HF 住院（HR=0.61，95%CI[0.43，0.86]，GRADE：“中度”）、全因住院（HR=0.51，95%CI[0.26，0.98]，GRADE：“中度”）和心血管住院（HR=0.56，95%CI[0.37，0.84]，GRADE：“中度”）方面优于依普利酮。坎尼酮在全因死亡率、复合结局和 HF 住院方面排名第一。非奈利酮在高钾血症（风险比[RR]=1.56，95%CI[0.89，2.74]，GRADE：“中度”）、肾损伤（RR=0.56，95%CI[0.24，1.29]）、任何不良事件（RR=0.84，95%CI[0.75，0.94]，GRADE：“中度”）、治疗中断（RR=0.89，95%CI[0.64，1.23]）和低血压（RR=1.06，95%CI[0.12，9.41]）方面排名第一。
MRA 在 HFrEF 中有效，但安全性存在差异。螺内酯和依普利酮的疗效相似，但依普利酮的安全性更高。非奈利酮是最安全的 MRA，坎尼酮则具有相当大的疗效，但这些 MRA 的证据很少。
