Tolerability of β‐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 β‐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 β‐blocker; the remaining four patients who did not receive β‐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 β‐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 β‐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 β‐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 β‐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 β‐blockers in addition to diuretics and vasodilators for the 6‐month observation period. β‐Blocker dosages were titrated, and three patients achieved the target β‐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.