Milrinone Therapy in Acute Heart Failure: Clinical Evidence, Hemodynamic Effects, and Safety Considerations

Background: Milrinone, a phosphodiesterase-III inhibitor, remains a commonly used inotropic agent in the management of acute heart failure (AHF), particularly in scenarios characterized by low cardiac output, end-organ hypoperfusion, or cardiogenic shock. Despite decades of clinical use, the evidence regarding its comparative effectiveness, hemodynamic benefits, and safety profile continues to evolve. Recent randomized trials, observational cohorts, meta-analyses, and contemporary heart failure guidelines provide updated insights into the clinical utility of milrinone in AHF. Objective: To systematically review and synthesize the current evidence on milrinone therapy in acute heart failure, focusing on: (1) clinical outcomes; (2) hemodynamic effects; and (3) safety considerations. Methods: A systematic evaluation of selected literature—including randomized controlled trials (e.g., OPTIME-CHF; DOREMI), meta-analyses, guideline recommendations (AHA/ACC/HFSA 2022; ESC 2021–2023), and contemporary reviews—was performed. Studies examining milrinone use in acute heart failure, acute decompensated heart failure, and cardiogenic shock were included. Data related to mortality, rehospitalization, hemodynamic response, adverse effects, and comparative performance against dobutamine were summarized narratively. Results: Evidence from comparative trials demonstrates that milrinone improves cardiac index and reduces pulmonary pressures, supporting its role in patients with low-output AHF. However, clinical outcomes such as mortality and rehospitalization show no consistent superiority over dobutamine, with some observational studies suggesting potential benefits in selected subgroups of acute decompensated heart failure. Meta-analyses remain heterogeneous, reflecting differences in study design and patient population. Safety findings indicate increased risk of arrhythmias and hypotension, particularly in patients with renal dysfunction or advanced shock. Guidelines recommend milrinone as an option for patients with preserved blood pressure, on chronic beta-blocker therapy, or requiring pulmonary vasodilation. Conclusions: Milrinone provides meaningful hemodynamic improvement in AHF and may offer clinical advantages in specific patient scenarios. Nevertheless, its overall impact on major clinical outcomes remains uncertain, and safety concerns persist. Individualized therapy guided by patient profile, hemodynamic status, and guideline recommendations is essential. Further high-quality trials are needed to clarify its optimal role in the modern management of acute heart failure.