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DRUG INFORMATION ROUNDS

Use of Combination Therapy with a β-Blocker and Milrinone in Patients with Advanced Heart Failure

Clinical Pharmacy Specialist, Department of Pharmacy, Henry Ford Hospital, Detroit, MI

Melissa L Thompson

PharmD student, South Carolina College of Pharmacy–Medical University of South Carolina campus, Charleston, SC

Reprints: Dr. Jennings, Department of Pharmacy, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48201, fax 313/916-1302, djennin1{at}hfhs.org

OBJECTIVE: To review the literature evaluating the clinical effects of combination therapy with a β-blocker and milrinone in patients with severe heart failure (HF).

DATA SOURCES: Literature was accessed through MEDLINE (1950–June 2009), PubMed (1966–June 2009), and International Pharmaceutical Abstracts (1970–June 2009), with combinations of the following terms: positive inotrope, milrinone, dobutamine, and β-receptor blocker. In addition, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: All articles that examined the effect of combination therapy with a β-blocker and milrinone on clinical endpoints in patients with advanced HF were assessed.

DATA SYNTHESIS: A search of the literature revealed 4 studies examining the clinical effects of combination therapy with a β-blocker and milrinone. Three of these studies were retrospective reviews, while one was a post hoc subgroup analysis from the OPTIME-CHF study. Concomitant therapy with milrinone and a β-blocker was well tolerated, with no significant increase in adverse events or deterioration in clinical status in any study. Tolerability rates for combination therapy ranged from 88% to 92%. In 2 of the studies, roughly 50% of the patients in the combination arm were able to be weaned off milrinone. One study suggested a mortality reduction in favor of combination therapy over milrinone alone, while another study suggested no difference in mortality with combination therapy versus milrinone monotherapy. One study suggested a potential increase in mortality when β-blocker therapy was withdrawn in patients who were started on milrinone. None of the studies demonstrated any significant differences in hospitalization rates. All of the studies were limited by their retrospective nature and small sample size.

CONCLUSIONS: Data are insufficient to make firm conclusions on the clinical benefit of combination therapy with a β-blocker and milrinone in patients with advanced HF, although it appears that this regimen is well tolerated and may allow weaning of inotropic support.

Key Words: β-adrenergic blocker, carvedilol, metoprolol, milrinone, positive inotrope

Published Online, September 29, 2009. www.theannals.com, DOI 10.1345/aph.1M357