European Heart Journal Advance Access published online on June 16, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl099
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1 Academic Unit of Cardiology, Department of Cardiology, Castle Hill Hospital, University of Hull, Castle Road, Cottingham, Kingston upon Hull, East Yorkshire, UK
* To whom correspondence should be addressed. Aims The Cardiac Resynchronization-Heart Failure study randomized patients with left ventricular ejection fraction Methods and 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). Conclusion 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.
Received January 23, 2006
Revised May 24, 2006
Accepted May 26, 2006
Clinical research
Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the Cardiac Resynchronization-Heart Failure (CARE-HF) trial extension phase]
John G.F. Cleland 1 *,
Jean-Claude Daubert 2,
Erland Erdmann 3,
Nick Freemantle 4,
Daniel Gras 5,
Lukas Kappenberger 6,
Luigi Tavazzi 7,
on behalf of The CARE-HF Study Investigators
2 Département de Cardiologie, Hôpital Pontchaillou, Rennes, France
3 Klinik III für Innere Medizin der Universität zu Köln, Cologne, Germany
4 University of Birmingham, Edgbaston, UK
5 Nouvelles Cliniques Nantaises, Nantes, France
6 Division of Cardiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
7 IRCCS Policlinico S. Matteo, Pavia, Italy
John G.F. Cleland, E-mail: j.g.cleland{at}hull.ac.uk
Abstract 
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.
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