Tolerability of beta-blockers in outpatients with refractory heart failure who were receiving continuous milrinone.
OBJECTIVE
To investigate the dosing, tolerability, and outcomes associated with the use of concomitant beta-blockers and inotropic therapy in patients with refractory heart failure during the first 6 months of their therapy.


METHODS
Retrospective review.


METHODS
University-based, tertiary care heart failure and transplant center.


METHODS
Sixteen inotrope-dependent outpatients with end-stage refractory heart failure who were receiving continuous intravenous milrinone. Of these patients, 12 also received an oral beta-blocker; the remaining four patients who did not receive beta-blockers served as the comparator group.


RESULTS
For each patient, the initial and final study drug doses of continuous intravenous milrinone and oral beta-blocker treatment, when applicable, were recorded over the 6-month period. Mean heart rate, blood pressure, ejection fraction, and oxygen consumption were measured, and 95% confidence intervals were calculated. Serum sodium and creatinine concentrations, as well as the creatinine clearance, were measured. In the 12 patients who received concomitant milrinone and beta-blockers, the mean baseline ejection fraction was approximately 18%, and they received milrinone for 18.6 weeks. Seven patients received carvedilol for 16.1 weeks, and five received metoprolol tartrate for 17.6 weeks. Dosages of the beta-blockers were titrated. Final daily doses were carvedilol 42.8 mg (95% confidence interval 20.3-65.4) and metoprolol 42.5 mg (95% confidence interval 28.0-57.2). Patients continued to receive other standard oral drug therapy for heart failure. One patient discontinued metoprolol and one discontinued carvedilol because of hypotension and/or worsening heart failure. Cardiac adverse events in the concomitant milrinone plus beta-blocker group were heart failure requiring hospitalization in 10 patients and ventricular arrhythmias in one.


CONCLUSIONS
Inotrope-dependent patients with refractory end-stage heart failure tolerated continuous intravenous milrinone plus beta-blockers in addition to diuretics and vasodilators for the 6-month observation period. Beta-blocker dosages were titrated, and three patients achieved the target beta-blocker dosage established for stage A-C heart failure. Additional studies are needed to determine the optimal selection and dosing of drug combinations in this population.
Earl
Grace L
GL
Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, Pennsylvania 19104, USA. g.earl@usip.edu
Verbos-Kazanas
Marybeth A
MA
Fitzpatrick
Jane M
JM
Narula
Jagat
J
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000188:drug therapy*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D000077261:Carvedilol; D003404:Creatinine / Q000097:blood / Q000652:urine; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006785:Hospitals, University; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D020105:Milrinone / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012964:Sodium / Q000097:blood; D014665:Vasodilator Agents / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002316:Cardiotonic Agents; D004232:Diuretics; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D012964:Sodium; D003404:Creatinine; D008790:Metoprolol; D020105:Milrinone