Impact of carvedilol and metoprolol on inappropriate implantable cardioverter-defibrillator therapy: the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy)

Abstract

Objectives: The goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study.

Background: The impact of carvedilol and metoprolol on inappropriate therapy in heart failure patients with devices has not yet been investigated.

Methods: All patients in the MADIT-CRT study who received a device (N = 1,790) were identified. Using time-dependent Cox regression analysis, we compared patients treated with different types of beta-blockers or no beta-blockers on the primary endpoint of inappropriate therapy, delivered as antitachycardia pacing (ATP) or shock therapy. Secondary endpoints were inappropriate therapy due to atrial fibrillation and atrial tachyarrhythmias, also evaluated as ATP or shock therapy.

Results: Inappropriate therapy occurred in 253 (14%) of 1,790 patients during a follow-up period of 3.4 ± 1.1 years. Treatment with carvedilol was associated with a significantly decreased risk of inappropriate therapy compared with metoprolol (hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.48 to 0.85]; p = 0.002). The reduction in risk was consistent for inappropriate ATP (HR: 0.66 [95% CI: 0.48 to 0.90]; p = 0.009) and inappropriate shock therapy (HR: 0.54 [95% CI: 0.36 to 0.80]; p = 0.002). The risk of inappropriate therapy caused by atrial fibrillation was also reduced in patients receiving carvedilol compared with metoprolol (HR: 0.50 [95% CI: 0.32 to 0.81]; p = 0.004). General use of beta-blockers (93%) and adherence in this study was high.

Conclusions: In heart failure patients undergoing either cardiac resynchronization therapy with a defibrillator or with an implantable cardioverter-defibrillator device, carvedilol was associated with a 36% lower rate of inappropriate ATP and shock therapy compared with metoprolol. Inappropriate therapy due to atrial fibrillation was associated with a 50% lower rate in patients receiving carvedilol compared with those receiving metoprolol. (MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy; NCT00180271).

Keywords: ATP; CI; CRT-D; HR; ICD; antitachycardia pacing; beta-blockers; cardiac resynchronization therapy with defibrillator; confidence interval; defibrillator; hazard ratio; heart failure; implantable cardioverter-defibrillator; inappropriate therapy.