Ahmed Saad Elsaeidy, Mohamed Abuelazm, Ramy Ghaly, Youssef Soliman, Ahmed Mazen Amin, Mohamed El-Gohary, Salem Elshenawy, Amith Reddy Seri, Basel Abdelazeem, Brijesh Patel, Christopher Bianco
{"title":"左西孟旦对晚期心力衰竭患者的疗效和安全性：随机对照试验的最新元分析","authors":"Ahmed Saad Elsaeidy, Mohamed Abuelazm, Ramy Ghaly, Youssef Soliman, Ahmed Mazen Amin, Mohamed El-Gohary, Salem Elshenawy, Amith Reddy Seri, Basel Abdelazeem, Brijesh Patel, Christopher Bianco","doi":"10.1007/s40256-024-00675-z","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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], <i>P</i> = 0.002; <i>I</i><sup>2</sup> = 75, <i>P</i> = 0.0005), with cumulative <i>z</i>-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], <i>P</i> = 0.01; <i>I</i><sup>2</sup> = 9, <i>P</i> = 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], <i>P</i> = 0.25; <i>I</i><sup>2</sup> = 70, <i>P</i> = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72–1.30], <i>P</i> = 0.84; <i>I</i><sup>2</sup> = 63, <i>P</i> = 0.03), or any adverse event (RR 1 [95% CI 0.73–1.37], <i>P</i> = 1.00, <i>I</i><sup>2</sup> = 0%, <i>P</i> = 0.70).</p><h3>Conclusion</h3><p>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.</p><h3>Registration</h3><p>PROSPERO identifier number (CRD42023487838).</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"24 6","pages":"775 - 790"},"PeriodicalIF":2.8000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40256-024-00675-z.pdf","citationCount":"0","resultStr":"{\"title\":\"The Efficacy and Safety of Levosimendan in Patients with Advanced Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials\",\"authors\":\"Ahmed Saad Elsaeidy, Mohamed Abuelazm, Ramy Ghaly, Youssef Soliman, Ahmed Mazen Amin, Mohamed El-Gohary, Salem Elshenawy, Amith Reddy Seri, Basel Abdelazeem, Brijesh Patel, Christopher Bianco\",\"doi\":\"10.1007/s40256-024-00675-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p><h3>Methods</h3><p>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.</p><h3>Results</h3><p>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], <i>P</i> = 0.002; <i>I</i><sup>2</sup> = 75, <i>P</i> = 0.0005), with cumulative <i>z</i>-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], <i>P</i> = 0.01; <i>I</i><sup>2</sup> = 9, <i>P</i> = 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], <i>P</i> = 0.25; <i>I</i><sup>2</sup> = 70, <i>P</i> = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72–1.30], <i>P</i> = 0.84; <i>I</i><sup>2</sup> = 63, <i>P</i> = 0.03), or any adverse event (RR 1 [95% CI 0.73–1.37], <i>P</i> = 1.00, <i>I</i><sup>2</sup> = 0%, <i>P</i> = 0.70).</p><h3>Conclusion</h3><p>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.</p><h3>Registration</h3><p>PROSPERO identifier number (CRD42023487838).</p></div>\",\"PeriodicalId\":7652,\"journal\":{\"name\":\"American Journal of Cardiovascular Drugs\",\"volume\":\"24 6\",\"pages\":\"775 - 790\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s40256-024-00675-z.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Cardiovascular Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s40256-024-00675-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Cardiovascular Drugs","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40256-024-00675-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景几项小型随机对照试验显示，间歇性非卧床左西孟旦给药对晚期心力衰竭患者有益，可预防心力衰竭再住院和死亡率。我们旨在调查有关间歇性左西孟旦在晚期心衰患者中的疗效和安全性的全部高质量证据。方法截至 2023 年 9 月，我们系统地回顾了 PubMed、Embase Cochrane、SCOPUS 和 Web of Science 中索引的随机对照试验。我们采用随机效应模型，以平均差（MD）估算连续性结果，以风险比（RR）估算二分类结果，并得出 95% 的置信区间（CI）。最后，我们采用了试验序列分析法来提高研究结果的可靠性，并采用了建议评估、发展和评价分级（GRADE）框架来进行确定性分级。与安慰剂相比，间歇性左西孟旦与左心室射血分数的改善有显著相关性（MD 6.39 [95% CI 3.04-9.73], P = 0.002; I2 = 75, P = 0.0005），≤1周后的累积z-score变化超过了监测界限，有利于左西孟旦，但未超过所需的信息量。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；I2 = 9，P = 0.36）。然而，我们发现左西孟旦和安慰剂在全因再住院率（RR 0.75 [95% CI 0.46-1.22]，P = 0.25；I2 = 70，P = 0.04）、无事件生存率（RR 0.97 [95% CI 0.72-1.30]，P = 0.84；I2 = 63，P = 0.结论在晚期心力衰竭患者中，间歇使用左西孟旦可显著改善左室射血分数、脑钠肽值和全因死亡率。注册PROSPERO识别码（CRD42023487838）。
The Efficacy and Safety of Levosimendan in Patients with Advanced Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials
Background
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.
Methods
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.
Results
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; I2 = 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; I2 = 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; I2 = 70, P = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72–1.30], P = 0.84; I2 = 63, P = 0.03), or any adverse event (RR 1 [95% CI 0.73–1.37], P = 1.00, I2 = 0%, P = 0.70).
Conclusion
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.
期刊介绍：
Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents.
Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations.
The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
