Pharmacodynamic Study of Carvedilol Versus Metoprolol in Heart Failure

• Status: Completed
• Trial end date: 2004-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Metoprolol succinate is a beta1-selective beta-blocker, becoming non-selective at higher doses, while carvedilol is non-selective. We examined whether metoprolol remained beta1-selective compared to carvedilol during dose up-titration in Class C heart failure (HF) Beta-blocker naïve patients.

METHODS: Twenty-five NYHA FC II-III HF patients were randomized to carvedilol or metoprolol. Patients were studied at baseline and after 2 weeks of up-titration (metoprolol at 25, 50, 100, and 200 mg daily; carvedilol IR at 3.125, 6.25, 12.5, 25 mg and 50mg twice daily). Beta2- blockade was determined by an infusion of terbutaline at 6 mg/kg over 1 hour. Glucose and potassium levels were serially measured at baseline, every 15 minutes for the 1st hour and 30 minutes for 2nd hour post-infusion. The median area under the curve (AUC) for glucose and potassium changes were calculated.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Collaborator: GlaxoSmithKline
• Treatments: Carvedilol; Metoprolol; Terbutaline

Criteria

Inclusion Criteria:

• Patients eligible for the study had objective evidence of systolic dysfunction (ejection fraction ≤40%), were >18 years of age, and were on stable optimal medical heart failure therapy excluding the use of beta-blockers within the previous 30 days.

Exclusion Criteria:

• . Patients were excluded for active viral myocarditis; hemodynamically significant valvular heart disease; hypertrophic cardiomyopathy, peripartum cardiomyopathy; contra-indications to beta-blockers (asthma or obstructive airway disease requiring scheduled bronchodilators or inhaled steroids), resting heart rate <55; supine blood pressure <85/50; second or third degree heart block); concomitant use of beta-agonists, beta-antagonists, or anti-arrhythmics; unstable angina; myocardial infarction or bypass surgery within 3 months; or significant renal insufficiency (creatinine >2.5 mg/dL), liver disease (transaminase levels > 3 fold above laboratory normal), or anemia.