Long-Term Extrapolation of Clinical Benefits Among Patients With Mild Heart Failure Receiving Cardiac Resynchronization Therapy: Analysis of the 5-Year Follow-Up From the REVERSE Study.
OBJECTIVE
This study sought to assess the lifelong extrapolated patient outcomes with cardiac resynchronization therapy (CRT) in mild heart failure (HF), beyond the follow-up of randomized clinical trials (RCTs).


BACKGROUND
RCTs have demonstrated short-term survival and HF hospitalization benefits of CRT in mild HF. We used data from the 5-year follow-up of the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) study to extrapolate survival and HF hospitalizations. We compared CRT-ON versus CRT-OFF and CRT defibrillators (CRT-D) versus CRT pacemakers (CRT-P).


METHODS
Multivariate regression models were used to estimate treatment-specific all-cause mortality, disease progression, and HF-related hospitalization rates. Rank-preserving structural failure time (RPSFT) models were used to adjust for protocol-mandated crossover in the survival analysis.


RESULTS
CRT-ON was predicted to increase survival by 22.8% (CRT-ON 52.5% vs. CRT-OFF 29.7%; hazard ratio [HR]: 0.45; p = 0.21), leading to an expected survival of 9.76 years (CRT-ON) versus 7.5 years (CRT-OFF). CRT-D showed a significant improvement in survival compared with CRT-P (HR: 0.47; 95% confidence interval [CI]: 0.25 to 0.88; p = 0.02) and were predicted to offer 2.77 additional life-years. New York Heart Association (NYHA) functional class II patients had a 30.6% higher HF hospitalization risk than class I (I vs. II incident rate ratio [IRR]: 0.69; 95% CI: 0.57 to 0.85; p < 0.001) and 3 times lower rate compared with class III (III vs.
2.98; 95% CI: 2.29 to 3.87; p < 0.001).


CONCLUSIONS
RPSFT estimates yielded results demonstrating clinically important long-term benefit of CRT in mild HF. CRT was predicted to reduce mortality, with CRT-D prolonging life more than CRT-P. NYHA functional class I/II patients were shown to have a significantly reduced risk of HF hospitalization compared with class III, leading to CRT reducing HF hospitalization rates.
Division of Cardiology, Medical University of South Carolina, Charleston, South Carolina. Electronic address: goldmr@musc.edu.
Michael R
MR
Gold
Health Economics and Epidemiology, ICON/Oxford Outcomes, Oxford, United Kingdom.
Amie
A
Padhiar
Health Economics and Epidemiology, ICON/Oxford Outcomes, Oxford, United Kingdom.
Stuart
S
Mealing
Health Economics and Epidemiology, ICON/Oxford Outcomes, Morristown, New Jersey.
Manpreet K
MK
Sidhu
Global Economics, Reimbursement and Evidence, Medtronic Global CRHF Headquarters, Mounds View, Minnesota.
Stelios I
SI
Tsintzos
Division of Cardiovascular Medicine, Ohio State University, Columbus, Ohio.
William T
WT
Abraham
D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*
cardiac resynchronization therapy; health economics; health policy; heart failure; rank-preserving structural failure time