Phosphodiesterase 3 inhibitors reduce the degradation of cellular cyclic AMP, leading to increased levels of cyclic AMP in cardiac and smooth muscle myocytes.

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The mechanism involves increased contractility on the left and right ventricles and dilation of systemic and pulmonary vessels. "inodilator" refers to its positive inotropic effect and ability to decrease preload and afterload.

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Milrinone has a stronger arterial and venous vasodilatory effect than dobutamine, but its chronotropic effect is lesser.​

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The Outcome of a Perspective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-HF) Trial

• Patients admitted with HF and a reduced ejection fraction who did not require an inotrope did not improve hospital mortality rate, 60-day mortality rate, or the composite incidence of death or readmission.

• Patients with CAD had an increase in postdischarge mortality (42% versus 36%) compared with placebo despite the short-term use of milrinone.

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The Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock (DOREMI) trial randomly assigned 192 patients with cardiogenic shock to receive either milrinone or dobutamine.

• The treatment groups did not differ significantly in the primary outcome, which is a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack, or stroke diagnosed by a neurologist, and initiation of renal replacement therapy. The primary outcome event occurred in 49% of the milrinone group and 54% of the dobutamine group (RR, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P=0.47).

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The agent of choice among heart failure patients requires short-term intravenous inotropic support in patients with preserved mean arterial pressure and right ventricular failure due to increased pulmonary afterload (e.g., pulmonary embolism, pulmonary arterial hypertension resulting from right ventricular failure, or following cardiac transplantation).

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