Abstract and Introduction
Abstract
Background: Prophylactic therapy with the implantable cardioverter defibrillator (ICD) reduces the mortality among patients with left ventricular dysfunction; however, life-prolonging device therapy has been shown to be associated with an increased risk for subsequent heart failure (HF) events. There are limited data on the effect of the primary types of HF medications, angiotensin converting enzyme inhibitors (ACE-I), and beta-blockers on HF progression in ICD-treated patients.
Methods: Multivariate Cox proportional hazards regression analysis was used to assess the effect of time-dependent medical therapy with ACE-I and beta-blockers on the development of HF in patients with an ICD in the Multicenter Automatic Defibrillator Trail (MADIT) II.
Results: In multivariate analysis, ICD therapy was associated with a significant 39% increase in the risk of HF as compared with conventional medical therapy. ACE-I and beta-blockers exhibited a graded efficacy for the reduction in the risk of HF events in ICD-treated patients: the greatest risk reduction of HF was seen in patients taking combination therapy (HR = 0.36, P < 0.001), followed by patients using beta-blockers only (HR = 0.51, P = 0.017) and ACE-I only (HR = 0.64, P = 0.071). Beta-blocker subtypes (metoprolol [HR = 0.49, P = 0.001] and carvedilol [HR = 0.58, P = 0.004]) exhibited similar efficacy. Consistent results were demonstrated when the combined endpoint of HF or death was assessed.
Conclusions: ICD-treated patients experience an increased risk for HF events that can be significantly attenuated by medical therapy with beta-blockers and ACE-inhibitors.
Introduction
Prophylactic therapy with the implantable cardioverter defibrillator (ICD) was shown to prolong survival in patients with left ventricular dysfunction. However, a recent analysis from the Multicenter Automatic Defibrillator Implantation Trail (MADIT) II has demonstrated that the reduction in the mortality risk is associated with a significant 39% increase in the risk of subsequent heart failure (HF) hospitalization. There are two possible main strategies for preventing HF in patients with an ICD: resynchronization therapy and optimized adjunctive medical therapy. In the COMPANION trial, resynchronization therapy was shown to decrease the risk of the combined endpoint of death from HF or HF hospitalization among patients with advanced HF and prolonged QRS complex. Beta-blockers and angiotensin converting enzyme inhibitors (ACE-I) have been shown to improve survival of HF patients and are considered class I medical therapies in these patients. However, there are limited data on the efficacy of adjuvant HF medications in the patients with the ICD.
The primary aims of the study were to assess the effect of ACE-I, beta-blockers, or their combination on the risk of the first HF hospitalization and combined endpoint of the first HF hospitalization or death in MADIT II patients. In a secondary analysis we also compared the efficacy of beta-blocker subtypes, and the benefit of ACE-I and angiotensin receptor blockers.