# Comparative Efficacy and Safety of Vasopressors and Inotropes in Acute Myocardial Infarction-Related Cardiogenic Shock: A Systematic Review and Network Meta Analysis of Randomized and Observational Studies

## TL;DR

This study compares the effectiveness and safety of different drugs used to treat heart failure in patients with heart attacks, finding that norepinephrine is safest and milrinone and dobutamine are equally effective.

## Contribution

The study provides updated evidence on vasopressor and inotrope efficacy in cardiogenic shock, highlighting norepinephrine's safety and the diminishing effect sizes over time.

## Key findings

- Norepinephrine is associated with lower arrhythmic risk and reduced refractory shock compared to dopamine and epinephrine.
- Milrinone and dobutamine show equivalent in-hospital mortality rates with high certainty.
- Historical studies showed larger effect sizes that have diminished over time, indicating a Proteus phenomenon.

## Abstract

This systematic review and network meta-analysis evaluated the comparative efficacy and safety of vasopressors and inotropes in patients with cardiogenic shock complicating acute myocardial infarction. Electronic databases were searched from inception to December 2025 for randomized controlled trials (RCTs) and observational studies that compared norepinephrine, epinephrine, dopamine, dobutamine, milrinone, and levosimendan. The primary outcome was all-cause mortality, and the secondary outcomes included arrhythmia and refractory shock. Data were synthesized using a frequentist random-effects network meta-analysis. The certainty of evidence was assessed using the GRADE framework. In total, 14 studies (N = 5,157) were included, comprising six RCTs and eight observational studies. The network geometry was connected via bridging observational data. In the modern era (post-2000), no single agent significantly reduced mortality compared with others. Milrinone and dobutamine were equivalent in terms of in-hospital mortality (odds ratio (OR) = 0.90, 95% confidence interval (CI) 0.69-1.19; high certainty). Norepinephrine was associated with a lower arrhythmic risk than dopamine and was superior to epinephrine, which significantly increased the risk of refractory shock (OR = 8.24, 95% CI = 1.61-42.18; moderate certainty) and mortality (OR = 1.63 vs. norepinephrine). Historical studies have shown large effect sizes that have diminished over time (the Proteus phenomenon). Norepinephrine is the preferred vasopressor due to its safety profile; however, the choice of inotrope between milrinone and dobutamine should be guided by patient physiology rather than survival expectations. Future research requires large-scale trials to detect modest mortality benefits in patients with diabetes.