Vasoactive drugs in cardiogenic shock: a systematic review and meta-analysis of randomized controlled trials

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Cardiogenic shock (n=1399). Intervention: Vasoactive drugs (epinephrine, milrinone, levosimendan, nitric oxide synthase inhibitors, adrecizumab) vs. Placebo or usual care (including norepinephrine, dobutamine, dopamine, or enoximone). Primary outcome: Acute mortality (death up to 30 days or hospital discharge) (RR 1.35, 95% CI 0.45-4.06, p=0.36).

Q: What does this research mean for the field?

There is insufficient evidence that any specific vasoactive drug reduces acute mortality compared to placebo or alternative agents in patients with cardiogenic shock. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ella Rose McNamee; Cara Wardman; Amy Boyle; Alex Warren; Alastair Proudfoot; Janus Christian Jakobsen; Bronagh Blackwood; Daniel F McAuley; Peter J. McGuigan

doi:10.1186/s12872-026-07012-z

November 14, 2026BMC Cardiovascular DisordersOpen Access

Vasoactive drugs in cardiogenic shock: a systematic review and meta-analysis of randomized controlled trials

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Key result

Vasoactive drugs fail to reduce acute mortality in cardiogenic shock across major drug comparisons.

Why the study?

Cardiogenic shock has an in-hospital mortality of 30–60% and 90% of patients require vasoactive drugs, prompting an evaluation of whether any vasoactive drug reduces mortality compared to placebo or usual care.

Does any vasoactive drug reduce acute mortality compared to placebo or usual care in adults with cardiogenic shock?

Key Points

To assess whether any vasoactive drug compared with placebo or usual care reduces acute mortality in adults with cardiogenic shock.
Systematic review and meta-analysis registered on PROSPERO (CRD42024614065), searching MEDLINE, Embase, and CENTRAL through 20th October 2026 without date or language restrictions.
Included randomized controlled trials of patients aged 16 years or older with cardiogenic shock (excluding post cardiotomy shock) evaluating any vasoactive drug aimed at increasing blood pressure or cardiac output.
The primary outcome was acute mortality (death up to 30 days or hospital discharge), synthesized using a random effects model across 13 trials (1399 patients).
No evidence of an effect on acute mortality was found for epinephrine versus norepinephrine or norepinephrine-dobutamine (3 studies, n = 114; RR, 1.35; 95% CI 0.45–4.06; p = 0.36; I² = 0%) or milrinone versus dobutamine or usual care (2 studies, n = 212; RR, 0.60; 95% CI 0.22–1.63; p = 0.31; I² = 60%).
Acute mortality did not differ for levosimendan versus enoximone or dobutamine (2 studies, n = 132; RR, 0.75; 95% CI 0.43–1.31; p = 0.32; I² = 40%) or nitric oxide synthase inhibitors versus placebo or usual care (3 studies, n = 505; RR, 0.92; 95% CI, 0.26–3.31; p = 0.82; I 2 = 58%).
The adrenomedullin antibody adrecizumab compared to placebo also showed no difference in acute mortality (1 study, n = 150; RR, 1.01; 95% CI 0.68–1.50; p = 0.95).

Study Design

Type

Meta-Analysis (n=1,399)

Multicenter

Yes

Structured PICO

Does any vasoactive drug reduce acute mortality compared to placebo or usual care in adults with cardiogenic shock?

P

Population

1,399 patients (1,144 with cardiogenic shock) across 13 randomized controlled trials of adults aged ≥16 years with non-post-cardiotomy cardiogenic shock followed for acute mortality up to 30 days or hospital discharge.

I

Intervention

Vasoactive drugs aimed at increasing blood pressure or cardiac output, analyzed by class: catecholamines (epinephrine), phosphodiesterase-3 inhibitors (milrinone), calcium sensitizers (levosimendan), nitric oxide synthase inhibitors (tilarginine [L-NMMA], L-NAME), and adrenomedullin antibody (adrecizumab).

C

Comparator

Placebo or usual care (including usual care vasoactive drugs such as norepinephrine, dopamine, dobutamine, or enoximone as defined in each trial).

O

Outcome

Acute mortality defined as death up to 30 days or hospital discharge (recorded in order of preference: 30 days, 28 days, hospital discharge, or ICU discharge).hard clinical

Main Result

Relative Risk: 1.35 (95% CI 0.45–4.06)

Absolute Event Rate: 41.7% vs 42.8%

p-value: p=0.36

This systematic review and meta-analysis found insufficient evidence (low to very low certainty) to support the mortality benefit of any specific vasoactive drug over another or usual care in adults with cardiogenic shock, highlighting a critical need for adequately powered RCTs.

Limitations

Trials were typically small, single-centre studies not powered to detect a difference in mortality, leading to a high risk of type II error and imprecision.
Exclusion of phase I heart failure studies at title/abstract screening if mortality was not reported in the abstract.
Lack of a consistent definition of cardiogenic shock across included trials.
Inability to extract cardiogenic shock subgroup mortality data from two relevant trials.
Many included studies did not report pre-specified outcomes due to the lack of a core outcome set for cardiogenic shock.
Low or very low certainty of evidence across all drug classes due to imprecision and risk of bias
Included trials were typically small, single-center studies (8 of 13 studies were single-center; median sample size 57)
High risk of type II error as required information sizes were not met in trial sequential analyses
No included trial was adequately powered to detect a difference in mortality
Unable to formally assess publication bias because no individual meta-analysis contained more than 10 studies

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

No vasoactive drug reduced acute mortality in cardiogenic shock; larger RCTs are required to identify effective agents.

Abstract

Background Cardiogenic shock (CS) has an in-hospital mortality of 30–60%. 90% of patients require vasoactive drugs. We conducted a systematic review and meta-analysis to assess whether, in adults with CS, any vasoactive drug, compared to placebo or usual care reduces mortality. Methods The protocol was registered on PROSPERO (CRD42024614065). We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials of vasoactive drugs in CS (last searched 20th October 2026). The primary outcome was acute mortality. Meta-analysis was performed using a random effects model. Results Of 5733 screened, 13 studies (1399 patients) were included. There was no evidence of an effect on acute mortality with epinephrine compared to norepinephrine or norepinephrine-dobutamine combination (3 studies, n = 114; RR, 1.35; 95% CI 0.45–4.06; p = 0.36; I² = 0%, low certainty of evidence), milrinone compared to dobutamine or usual care (2 studies, n = 212; RR, 0.60; 95% CI 0.22–1.63; p = 0.31; I² = 60%, low certainty of evidence), levosimendan compared to enoximone or dobutamine (2 studies, n = 132; RR, 0.75; 95% CI 0.43–1.31; p = 0.32; I² = 40%, very low certainty of evidence), nitric oxide synthase inhibitors compared to placebo or usual care (3 studies, n = 505; RR, 0.92; 95% CI, 0.26–3.31; p = 0.82, I 2 = 58%, low certainty of evidence) or the adrenomedullin antibody adrecizumab compared to placebo (1 study, n = 150; RR, 1.01; 95% CI 0.68–1.50; p = 0.95, low certainty of evidence). Conclusions We found insufficient evidence to support use of any specific vasoactive drug in CS.

Discussion

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Cite This Study

McNamee et al. (2026) conducted a meta-analysis in Cardiogenic shock (n=1,399). Vasoactive drugs (epinephrine, milrinone, levosimendan, nitric oxide synthase inhibitors, adrecizumab) vs. Placebo or usual care (including norepinephrine, dobutamine, dopamine, or enoximone) was evaluated on Acute mortality (death up to 30 days or hospital discharge) (RR 1.35, 95% CI 0.45-4.06, p=0.36). Vasoactive drugs showed no significant effect on acute mortality in cardiogenic shock across comparisons including epinephrine vs norepinephrine and milrinone vs dobutamine.

synapsesocial.com/papers/6af9ebcdd393cbc380a04fd7 https://doi.org/10.1186/s12872-026-07012-z

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Vasoactive drugs in cardiogenic shock: a systematic review and meta-analysis of randomized controlled trials

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Vasoactive drugs in cardiogenic shock: a systematic review and meta-analysis of randomized controlled trials

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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