Faculty of Medicine, Benha University, Benha, Egypt.
Faculty of Medicine, Tanta University, Tanta, Egypt.
Am J Cardiovasc Drugs. 2024 Nov;24(6):775-790. doi: 10.1007/s40256-024-00675-z. Epub 2024 Sep 11.
Intermittent ambulatory levosimendan administration has been shown in several small randomized controlled trials to benefit patients with advanced heart failure, preventing heart failure rehospitalization and mortality. We aim to investigate the totality of high-quality evidence regarding the efficacy and safety of intermittent levosimendan in advanced heart failure patients.
Up to September 2023, we systematically reviewed the randomized controlled trials indexed in PubMed, Embase Cochrane, SCOPUS, and Web of Science. We used mean difference (MD) to estimate the continuous outcomes, and risk ratio (RR) for the dichotomous outcomes with a 95% confidence interval (CI), using the random-effects model. Ultimately, a trial sequential analysis was employed to enhance the reliability of our findings and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for certainty leveling.
Fifteen randomized controlled trials with 1181 patients were included. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction compared with placebo (MD 6.39 [95% CI 3.04-9.73], P = 0.002; I = 75, P = 0.0005), with cumulative z-score of change after ≤ 1 week passing the monitoring boundaries, favoring the levosimendan, but did not cross the required information size. Additionally, levosimendan reduced the all-cause mortality rate (RR 0.60 [95% CI 0.40-0.90], P = 0.01; I = 9, P = 0.36). However, we found no difference between levosimendan and placebo in all-cause rehospitalization rate (RR 0.75 [95% CI 0.46-1.22], P = 0.25; I = 70, P = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72-1.30], P = 0.84; I = 63, P = 0.03), or any adverse event (RR 1 [95% CI 0.73-1.37], P = 1.00, I = 0%, P = 0.70).
In patients with advanced heart failure, intermittent levosimendan significantly improved left ventricular ejection fraction, brain natriuretic peptide values, and all-cause mortality rate. Levosimendan use is not associated with a change in rehospitalization or event-free survival.
PROSPERO identifier number (CRD42023487838).
间歇性口服左西孟旦在几项小型随机对照试验中已被证明对晚期心力衰竭患者有益，可预防心力衰竭再住院和死亡。我们旨在调查关于晚期心力衰竭患者间歇性左西孟旦疗效和安全性的高质量证据的全貌。
截至 2023 年 9 月，我们系统地检索了 PubMed、Embase Cochrane、SCOPUS 和 Web of Science 中索引的随机对照试验。我们使用均数差（MD）来估计连续性结局，使用风险比（RR）来估计二分类结局，并使用 95%置信区间（CI），使用随机效应模型。最终，我们使用试验序贯分析来提高我们研究结果的可靠性，并使用推荐评估、制定与评估分级（GRADE）框架进行确定性水平分级。
纳入了 15 项随机对照试验，共 1181 例患者。与安慰剂相比，间歇性左西孟旦显著提高了左心室射血分数（MD 6.39 [95% CI 3.04-9.73]，P = 0.002；I = 75，P = 0.0005），在≤1 周内改变后的累积 z 分数超过监测边界，有利于左西孟旦，但未超过所需信息大小。此外，左西孟旦降低了全因死亡率（RR 0.60 [95% CI 0.40-0.90]，P = 0.01；I = 9，P = 0.36）。然而，我们发现左西孟旦与安慰剂在全因再住院率（RR 0.75 [95% CI 0.46-1.22]，P = 0.25；I = 70，P = 0.04）、无事件生存率（RR 0.97 [95% CI 0.72-1.30]，P = 0.84；I = 63，P = 0.03）或任何不良事件（RR 1 [95% CI 0.73-1.37]，P = 1.00，I = 0%，P = 0.70）方面无差异。
在晚期心力衰竭患者中，间歇性左西孟旦显著改善了左心室射血分数、脑利钠肽值和全因死亡率。左西孟旦的使用与再住院或无事件生存率的变化无关。
PROSPERO 标识符编号（CRD42023487838）。
