Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase].
OBJECTIVE
The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction < or =35%, markers of cardiac dyssynchrony, and persistent moderate or severe symptoms of heart failure despite pharmacological therapy, to implantation of a cardiac resynchronization therapy (CRT) device or not. The main study observed substantial benefits on morbidity and mortality during a mean follow-up of 29.4 months [median 29.6, interquartile range (IQR) 23.6-34.6]. Prior to study closure, an extension phase lasting a further 8 months (allowing time for data analysis and presentation) was declared during which cross-over was discouraged.


RESULTS
This was an extension of the already reported open-label randomized trial described above. The primary outcome of the extension phase was all-cause mortality from the time of randomization to completion of the extension phase. The secondary outcome was mode of death. The mean follow-up was 37.4 months (median 37.6, IQR 31.5-42.5, range 26.1-52.6 months). There were 154 deaths (38.1%) in 404 patients assigned to medical therapy and 101 deaths (24.7%) in 409 patients assigned to CRT (hazard ratio 0.60, 95% CI 0.47-0.77, P<0.0001) without evidence of heterogeneity in pre-specified subgroups. A reduction in the risk of death due to heart failure (64 vs. 38 deaths; hazard ratio 0.55, 95% CI 0.37-0.82, P=0.003) and sudden death was observed (55 vs. 32; hazard ratio 0.54, 95% CI 0.35-0.84, P=0.005).


CONCLUSIONS
The benefits of CRT observed in the main trial persist or increase with longer follow-up. Reduction in mortality was due to fewer deaths both from worsening heart failure and from sudden death.
Cleland
John G F
JG
Academic Unit of Cardiology, Department of Cardiology, Castle Hill Hospital, University of Hull, Castle Road, Cottingham, Kingston upon Hull, East Yorkshire, UK. j.g.cleland@hull.ac.uk
Daubert
Jean-Claude
JC
Erdmann
Erland
E
Freemantle
Nick
N
Gras
Daniel
D
Kappenberger
Lukas
L
Tavazzi
Luigi
L
D000368:Aged; D002304:Cardiac Pacing, Artificial / Q000401:mortality*; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010138:Pacemaker, Artificial; D016019:Survival Analysis