Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta‐Analysis

Abstract

Despite advancements in modern medicine, the treatment of acute heart failure (AHF) after acute myocardial infarction (AMI) remains challenging. Milrinone is effective in the treatment of chronic congestive heart failure, but its safety and efficacy in patients with AHF after AMI have not been systematically evaluated. This meta-analysis was performed to assess the safety and efficacy of milrinone in patients with AHF after AMI. We used a pre-designed protocol to search electronic databases for randomized trials assessing milrinone for the treatment of AHF after AMI. Data were abstracted from relevant studies. Heteroge-neity was assessed qualitatively using a Q test and quantified using the I 2 statistic. Pooled risk estimates with 95% confidence intervals (CIs) were obtained using fixed-effects models unless substantial heterogeneity was observed (I 2 ≥ 50% and heterogene-ity p ≤ 0.1). Four randomized trials met the inclusion criteria. However, there were no significant differences in deaths, blood pressure, premature ventricular contractions, gastrointestinal reactions, or ventricular tachycardia or fibrillation (all p > 0.05) between control group and milrinone treatment group. Pooled estimates showed that milrinone significantly increased the left ventricular ejection fraction (MD 5.69; 95% CI 4.27 to 7.10; p < 0.00001) and cardiac output (MD 0.35, 95% CI: 0.13 to 0.56; p = 0.002, I 2 = 24%). While studies to date are few and limited by small sample sizes and poor quality, they suggest that treatment with milrinone may be safe and effective for patients with AHF after AMI. However, this meta-analysis did not show that milrinone could improve prognosis or the survival rate. Despite the substantial progress in medicine in recent decades [1], acute myocardial infarction (AMI) remains one of the leading causes of death and disability around the world [2,3]. After an AMI, about 40% of patients develop left ventricular dysfunction [4], and acute heart failure (AHF) is a common complication of AMI. The AHF epidemic, with its high morbidity , mortality, readmissions and costs, represents a tremendous challenge to the healthcare community and society as a whole [5-7]. Thus, successful treatment of AHF after AMI still remains a difficult task to accomplish. Decreased cardiac contractility plays a central role in sys-tolic AHF, making positive inotropics an essential part of AHF treatment [8]. Milrinone is a type III phosphodiesterase (PDE) inhibitor that can prevent the degradation of adenosine monophosphate-cAMP, thus leading to an increase in calcium ion concentration and ultimately improving myocardial con-tractility [9,10]. By increasing the cAMP concentration, PDE inhibitors also increase the removal of calcium from the vas-cular smooth muscle cells [11]. This, in turn, leads to cellular relaxation and vasodilation. Therefore, in addition to being a positive inotropic, milrinone also decreases the afterload. Milrinone has been widely used to support circulation in patients with severe AHF and acute exacerbations ...

2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

“…Leki inotropowe, zwłaszcza te działające w mechanizmie adrenergicznym, mogą powodować tachykardię zatokową oraz wywoływać niedokrwienie mięśnia sercowego i zaburzenia rytmu serca, dlatego wymagane jest monitorowanie EKG w trakcie ich podawania. Istnieją wieloletnie wątpliwości pochodzące z badań, w których stosowano przerywane lub ciągłe wlewy z leków inotropowych, dotyczące zwiększania śmiertelności w AHF z powodu stosowania leków z tej grupy [559][560][561][562][563]575]. W każdym przypadku leki o działaniu inotropowym należy podawać ostrożnie, zaczynając od raczej małych dawek, zwiększając je w trakcie precyzyjnego monitorowania.…”

Methodological Perspectives from ‘Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta‐analysis’

“…

We read with a great interest the paper by Tang et al [1]. In this study, the authors identified that milrinone significantly improves cardiac function in patients with acute heart failure after acute myocardial infarction.

…”

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

“…Three meta-analyses have evaluated milrinone in critically ill patients [3–5]. One meta-analysis included adult cardiac surgery patients and observed that milrinone was associated with a significant increase in mortality while an update of the review found no significant effects [4, 5].…”

“…One meta-analysis included adult cardiac surgery patients and observed that milrinone was associated with a significant increase in mortality while an update of the review found no significant effects [4, 5]. One other meta-analysis evaluated milrinone for the treatment of acute heart failure after acute myocardial infarction and suggested that milrinone might be safe and effective in these patients [3]. Unfortunately, only four trials with a limited number of 303 patients were included.…”

“…None of them were based upon a previously published protocol [3–5]. They lacked or had insufficient assessment of the risk of bias, and bias risks were insufficiently incorporated in the analyses and conclusions.…”