Key Trials Proving CRTD Improves Patient Outcomes
The COMPANION and CARE-HF trials definitively proved that cardiac resynchronization therapy devices (CRTD) improve mortality and morbidity in heart failure patients with reduced ejection fraction and ventricular dyssynchrony. 1
Primary Evidence: COMPANION Trial
The COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial was the landmark study that established CRTD efficacy 1:
- Enrolled 1,520 patients with NYHA class III-IV heart failure, LVEF ≤35%, QRS duration ≥120 ms, and sinus rhythm 1
- Three-arm design: optimal medical therapy alone vs. CRT-pacemaker (CRT-P) vs. CRT-defibrillator (CRT-D) 1, 2
- Primary endpoint: Combined all-cause mortality and all-cause hospitalization 2, 3
COMPANION Results - Mortality Benefits:
- CRT-D reduced all-cause mortality by 36% (P = 0.003) 1
- CRT-P reduced mortality by 24% (P = 0.059, nearly significant) 1
- Absolute risk reduction with CRT-D was 8.6% for cardiovascular death or hospitalization, with a number needed to treat of 12 over 16 months 1
COMPANION Results - Morbidity Benefits:
- CRT reduced combined death or hospitalization by 35-40%, primarily driven by a 76% reduction in hospitalization rates 1
- CRT reduced cardiac hospitalizations by 34-37% per patient-year of follow-up 2
- Heart failure hospitalizations decreased by 41-44% per patient-year 2
Primary Evidence: CARE-HF Trial
The CARE-HF (Cardiac Resynchronization in Heart Failure) trial provided complementary evidence 1:
- Enrolled 813 patients with NYHA class III-IV, LVEF ≤35%, QRS ≥120 ms (with additional dyssynchrony criteria if QRS 120-149 ms) 1
- Design: Optimal medical therapy vs. CRT-P only 1, 4
- Mean follow-up: 29.4 months 1
CARE-HF Results:
- CRT-P reduced all-cause mortality by 36% (P < 0.002) 1
- Extension study showed 40% mortality reduction (P < 0.0001), mainly from reduced heart failure deaths 1
- Heart failure hospitalizations reduced by 52% 1
- Absolute risk reduction of 16.6% with number needed to treat of 6 1
Supporting Evidence: Mild-to-Moderate Heart Failure
MADIT-CRT and RAFT trials extended CRTD benefits to less symptomatic patients 1:
MADIT-CRT:
- Enrolled 3,618 patients with NYHA class I (15%) and II (85%), LVEF ≤30%, QRS ≥130 ms 1
- Reduced death or heart failure events by 34% (relative risk reduction) 1
- Mortality alone was not significantly reduced 1
RAFT:
- Enrolled patients with NYHA class II (80%) and III (20%), LVEF ≤30%, QRS ≥120 ms 1
- Reduced death or heart failure hospitalization by 25% 1
- All-cause mortality reduced by 25% (P = 0.003) 1
Additional Benefits Across All Trials
Beyond mortality and hospitalization, these trials consistently demonstrated 1:
- Symptom improvement: NYHA class decreased by 0.5-0.8 points 1
- Exercise capacity: 6-minute walk distance increased by 20%, peak oxygen consumption by 10-15% 1
- Cardiac remodeling: LV end-systolic volume reduced by 18% at 3 months and 26% at 18 months 1
- LVEF improvement: Increased by 3.7% at 3 months and 6.9% at 18 months 1
- Quality of life: Sustained improvements across all trials 1
Important Caveats
QRS duration and morphology matter significantly 1:
- Greatest benefit occurs with QRS ≥150 ms and left bundle branch block (LBBB) morphology 1
- Benefit magnitude declines with shorter QRS duration 1
- Non-LBBB patients show less pronounced benefit compared to LBBB patients 1
Patient selection criteria from trials 1:
- All major trials required sinus rhythm (except RAFT, which included 13% with controlled atrial fibrillation) 1
- Patients needed to be on optimal medical therapy including ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists 1
- Class IV patients needed to be ambulatory with no hospitalizations in the preceding month 1