Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure - OPTIME-CHF


OPTIME-CHF was a randomized trial of short-term intravenous (IV) milrinone versus placebo in patients with decompensated systolic heart failure for whom inotropic therapy was not felt to be mandatory.


Compared with placebo, use of IV milrinone in decompensated systolic heart failure will result in fewer hospital days in short-term follow-up by either reducing initial length of stay or preventing readmission.

Study Design

Study Design:

Patients Enrolled: 951
NYHA Class: 7% class II, 46% class III, 47% class IV
Mean Follow Up: 60 days
Mean Patient Age: Mean 65 years
Female: 29
Mean Ejection Fraction: Mean 23 ± 8%

Patient Populations:

Adult patients with ejection fraction <40% and chronic heart failure hospitalized for an exacerbation of heart failure


1) Inotropic therapy deemed essential (e.g., shock).
2) Active myocardial ischemia within three months.
3) Atrial fibrillation with rapid ventricular response.
4) Sustained ventricular arrhythmia.
5) Baseline blood pressure <80 mm Hg.
6) Baseline creatinine >3.0 mg/dl.

Primary Endpoints:

Cardiovascular-related hospital days, or days deceased, within 60 days of randomization

Secondary Endpoints:

1) Proportion of patients failing therapy because of adverse events or worsening heart failure at 48 hours.
2) Proportion of patients achieving target doses of ACE inhibitor.
3) Symptoms and heart failure score.
4) Initial hospital length of stay.
5) Hospital days from discharge to 60 days postrandomization.
6) Mortality.

Drug/Procedures Used:

IV milrinone 0.5 μg/kg/min for 48-72 hours, versus placebo, initiated within 48 hours of hospital admission. The dose could be decreased to 0.375 μg/kg/min for hypotension or increased to 0.750 μg/kg/min for lack of effect.

Concomitant Medications:

In-hospital treatments for placebo and milrinone groups, respectively, included: oral diuretics (60% vs. 61%), IV diuretics (82% vs. 77%), angiotensin-converting enzyme (ACE) inhibitors (74% vs. 73%), beta-blockers (20% vs. 20%), and angiotensin receptor blockers (13% vs. 14%).

Principal Findings:

The primary endpoint of cardiovascular hospital days at 60 days was not significantly different between milrinone and placebo groups (mean 12.3 vs. 12.5 days, p=NS), nor were there differences in the initial hospital length of stay (mean 7.0 vs. 7.0 days, p=NS) or number of subsequent cardiac-related hospital days (mean 5.7 vs. 5.9 days, p=NS).

Sustained hypotension (10.7% vs. 3.2%, p<0.001) and new atrial fibrillation or flutter (4.6% vs. 1.5%, p=0.004) were more common for milrinone than placebo subjects, while heart failure progression and heart failure symptom scores were not different.


Routine use of IV milrinone for decompensated heart failure was not associated with a reduction in hospital-based resource utilization at 60 days and was associated with increased risk of hypotension and atrial arrhythmias.


Cuffe MS, Califf RM, Adams KF Jr, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 2002;287:1541-7.

Keywords: Milrinone, Follow-Up Studies, Hypotension, Heart Failure, Systolic, Cardiotonic Agents, Length of Stay

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