Safety and clinical utility of long-term intravenous milrinone in advanced heart failure

Few data are available on the long-term safety or clinical utility of the inodilator agent milrinone. We designed a prospective, nonrandomized, observational trial in a cohort of 71 patients who had demonstrated dependence on inotropic therapy, had been clinically stable on an inotropic regimen (milrinone, dobutamine, or both) for ≥72 hours, and had been given intravenous milrinone for >72 hours. Group I (n = 22) patients required treatment with both milrinone and dobutamine to achieve stability; group II (n = 49) patients attained stability initially with either milrinone (subgroup IIA) or dobutamine (subgroup IIB), but later required adjunctive therapy with the other inotropic agent for continued hemodynamic support. Of the 71 patients, 38% required mechanical intervention to achieve hemodynamic stability, and 68% were successfully bridged to heart transplantation. Patients were maintained on milrinone therapy for as long as 8 weeks and demonstrated a low incidence of adverse cardiac (7%) or noncardiac (4%) events. Subgroup IIA (28%) had significantly less need than subgroup IIB (52%) for mechanical intervention using an intraaortic balloon pump (p = 0.05), although mortality rates while awaiting transplantation were statistically similar in subgroups IIA (28%) and IIB (35%). Significant improvements from baseline values were noted at the time of transplantation for all aspects of systemic hemodynamics, indicating sustained long-term hemodynamic effects. Long-term intravenous milrinone therapy is safe and well tolerated, and it provides hemodynamic and metabolic support as a pharmacologic bridge to transplantation. The findings also suggest that milrinone as primary inodilator therapy may be associated with less need for mechanical ventricular support.