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


METHODS
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 beta-receptor blocker. In addition, reference citations from publications identified were reviewed.


METHODS
All articles that examined the effect of combination therapy with a beta-blocker and milrinone on clinical endpoints in patients with advanced HF were assessed.


RESULTS
A search of the literature revealed 4 studies examining the clinical effects of combination therapy with a beta-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 beta-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 One study suggested a potential increase in mortality when beta-blocker therapy was withdrawn in patients who were started on milrinone.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 beta-blocker and milrinone in patients with advanced HF, although it appears that this regimen is well tolerated and may allow weaning of inotropic support.
Department of Pharmacy, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48201, USA. djennin1@hfhs.org
Douglas L
DL
Jennings
Melissa L
ML
Thompson
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020105:Milrinone / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D020105:Milrinone