Milrinone is a bipyridine derivative with positive inotropic and vasodilating properties. The intravenous form of the drug has been approved by the Food and Drug Administration (FDA) for short-term management of congestive heart failure (CHF). The FDA has requested additional mortality data prior to approval of the oral form. Milrinone produces positive inotropic and vasodilating effects through unknown mechanisms, and causes a dose-dependent increase in cardiac index and a decrease in systemic vascular resistance and pulmonary capillary wedge pressure. It is extensively absorbed following oral administration with an elimination half-life of approximately 1.5–2 hours and a corresponding duration of action of 3–6 hours. Its major route of elimination is renal (83 percent). The intravenous dose is 50 μg/kg given over ten minutes, followed by a maintenance infusion of 0.375–0.75 μg/kg/min titrated to the desired hemodynamic response. The average effective oral dosage is 7.5–10 mg four to six times daily. Milrinone is most effective in the short-term management of CHF where the majority (60–80 percent) of patients have symptomatic and hemodynamic improvement as well as increases in exercise duration. However, many patients do not derive long-term benefit from milrinone therapy. Available evidence suggests that milrinone does not arrest the natural progression of CHF, and some investigators feel it may actually worsen CHF and shorten patients' length of survival. Milrinone has been generally well tolerated with a low risk of major organ toxicity. The most common adverse reactions with intravenous milrinone include ventricular arrhythmias (12 percent) and supraventricular arrhythmias (4 percent). Oral milrinone may cause gastrointestinal disturbances (11 percent), cardiac arrhythmias (7 percent), headache (7 percent), dizziness (6 percent), palpitations (6 percent), fatigue (3 percent), tachycardia (2 percent), and increased hepatic enzymes (2 percent). Although not proven, the major concern with milrinone is its potential to be proarrhythmic, leading to a higher incidence of sudden death in patients treated over the long term. Experience with milrinone indicates that its usefulness may be limited to the short-term treatment of CHF. Until mortality evaluations are complete, the role of milrinone in the long-term management of CHF will remain undefined.
Short-term treatment with LCZ696 in patients with stable chronic heart failure: effect on biomarkers
