Tolerability of beta-blockers in outpatients with refractory heart failure who were receiving continuous milrinone

STUDY 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. DESIGN: Retrospective review. SETTING: University-based, tertiary care heart failure and transplant center. PATIENTS: 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. MEASUREMENTS AND MAIN 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. CONCLUSION: 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.