The effect of cardiac resynchronization without a defibrillator on morbidity and mortality: an individual patient data meta-analysis of COMPANION and CARE-HF

Abstract

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality for patients with heart failure, reduced left ventricular ejection fraction, QRS duration >130 ms and in sinus rhythm. The aim of this study was to identify patient characteristics that predict the effect, specifically, of CRT pacemakers (CRT-P) on all-cause mortality or the composite of hospitalization for heart failure or all-cause mortality.

Methods and results: We conducted an individual patient data meta-analysis of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) and Cardiac Resynchronization-Heart Failure (CARE-HF) trials. Only patients assigned to CRT-P or control (n = 1738) were included in order to avoid confounding from concomitant defibrillator therapy. The influence of baseline characteristics on treatment effects was investigated. Median age was 67 (59-73) years, most patients were men (70%), 68% had a QRS duration of 150-199 ms and 80% had left bundle branch block. Patients assigned to CRT-P had lower rates for all-cause mortality (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.56-0.81; p < 0.0001) and the composite outcome (HR 0.67, 95% CI 0.58-0.78; p < 0.0001). No pre-specified characteristic, including sex, aetiology of ventricular dysfunction, QRS duration (within the studied range) or morphology or PR interval significantly influenced the effect of CRT-P on all-cause mortality or the composite outcome. However, CRT-P had a greater effect on the composite outcome for patients with lower body surface area and those prescribed beta-blockers.

Conclusions: Cardiac resynchronization therapy-pacemaker reduces morbidity and mortality in appropriately selected patients with heart failure. Benefits may be greater in smaller patients and in those receiving beta-blockers. Neither QRS duration nor morphology independently predicted the benefit of CRT-P.

Clinical trial registration: COMPANION, NCT00180258; CARE-HF, NCT00170300.

Keywords: Body surface area; Cardiac resynchronization therapy; Heart failure; Individual patient data meta-analysis; Mortality; Sex.

© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1

(A) Effect of cardiac resynchronization therapy pacemaker (CRT‐P) on all‐cause mortality in clinical subgroups. (B) Effect of CRT‐P on heart failure hospitalization or death in clinical subgroups. ACEi, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure; CI, confidence interval; HR, hazard ratio; IHD, ischaemic heart disease; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.

Figure 2

(A) Effect of cardiac resynchronization therapy pacemaker (CRT‐P) on all‐cause mortality stratified by QRS duration. Test for heterogeneity p = 0.104. (B) Effect of CRT‐P on heart failure hospitalization or death stratified by QRS duration. Test for heterogeneity p = 0.269. CI, confidence interval.

Figure 3

(A) Effect of cardiac resynchronization therapy pacemaker (CRT‐P) on all‐cause mortality stratified by QRS morphology. Test for heterogeneity p = 0.506. (B) Effect of CRT‐P on heart failure hospitalization or death stratified by QRS morphology. Test for heterogeneity p = 0.089. CI, confidence interval.

Figure 4

(A) Effect of cardiac resynchronization therapy pacemaker (CRT‐P) on all‐cause mortality stratified by height, weight and body surface area (BSA) tertiles. Tests for heterogeneity p = 0.128, 0.148 and 0.139, respectively. (B) Effect of CRT‐P on heart failure hospitalization or death stratified by height, weight and BSA tertiles. Tests for heterogeneity p = 0.028, 0.039 and 0.027, respectively. CI, confidence interval; HR, hazard ratio.