Implantable Cardioverter-Defibrillators in Trials of Drug Therapy for Heart Failure: A Systematic Review and Meta-Analysis

Abstract

BACKGROUND Medical therapy for heart failure with reduced ejection fraction evolved since trials validated the use of implantable cardioverter-defibrillators (ICDs). We sought to evaluate the performance of ICDs in reducing mortality in the era of modern medical therapy by means of a systematic review and meta-analysis of contemporary randomized clinical trials of drug therapy for heart failure with reduced ejection fraction. METHODS AND RESULTS We systematically identified randomized clinical trials that evaluated drug therapy in patients with heart failure with reduced ejection fraction that reported mortality. Studies that enrolled <1000 patients, patients with left ventricular ejection fraction >40%, or patients in the acute phase of heart failure and study treatment with devices were excluded. We identified 8 randomized clinical trials, including 31 701 patients of whom 3631 (11.5%) had an ICD. ICDs were associated with a lower risk of all-cause mortality (relative risk [RR], 0.85; 95% CI, 0.78-0.94) and sudden cardiac death (RR, 0.49; 95% CI, 0.40-0.61). Results were consistent among studies published before and after 2010. In meta-regression analysis, the proportion of nonischemic etiology did not affect the associated benefit of ICD. CONCLUSIONS In our meta-analysis of contemporary randomized trials of drug therapy for heart failure with reduced ejection fraction, the rate of ICD use was low and associated with a decreased risk in both all-cause mortality and sudden cardiac death. This benefit was still present in trials with new medical therapy.

Keywords: all‐cause mortality; heart failure with reduced ejection fraction; implantable cardioverter–defibrillators; sudden cardiac death.

Figure 1. Flowchart diagram illustrating studies selection methodology.

ICD indicates implantable cardioverter–defibrillator; and RCT, randomized clinical trial.

Figure 2. Forest plots comparing patients with ICD vs without ICD for the outcome all‐cause death.

Pooled estimates were calculated by random effects. ATMOSPHERE indicates Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure; BEST, Beta‐Blocker Evaluation of Survival Trial; CHARM‐Added, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Added Trial; CHARM‐Alt, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Alternative Trial; CORONA, Controlled Rosuvastatin Multinational Trial in Heart Failure; EMPHASIS‐HF, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure; ICD, implantable cardioverter–defibrillator; M–H, Mantel‐Haenszel methods; PARADIGM‐HF, Prospective Comparison of ARNI (Angiotensin Receptor‐Neprilysin Inhibitor) with ACEI (Angiotensin‐Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial; and WARCEF, Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction.

Figure 3. Forest plots comparing patients with ICD vs without ICD for the outcome sudden cardiac death.

Pooled estimates were calculated by random effects. CHARM‐Added indicates Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Added Trial; CHARM‐Alt, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity ‐ Alternative Trial; CORONA, Controlled Rosuvastatin Multinational Trial in Heart Failure; EMPHASIS‐HF, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure; ICD, implantable cardioverter–defibrillator; M–H, Mantel‐Haenszel methods; PARADIGM‐HF, Prospective Comparison of ARNI (Angiotensin Receptor‐Neprilysin Inhibitor) with ACEI (Angiotensin‐Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial; and WARCEF, Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction.