European Heart Journal Advance Access originally published online on June 16, 2006
European Heart Journal 2006 27(16):1928-1932; doi:10.1093/eurheartj/ehl099
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Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial extension phase]
1 Academic Unit of Cardiology, Department of Cardiology, Castle Hill Hospital, University of Hull, Castle Road, Cottingham, Kingston upon Hull, East Yorkshire, UK
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
Received 23 January 2006; revised 24 May 2006; accepted 26 May 2006; online publish-ahead-of-print 16 June 2006.
* Corresponding author. Tel: +44 1482 624 084; fax: +44 1482 624 085. E-mail address: j.g.cleland{at}hull.ac.uk
See page 1891 for the editorial comment on this article (doi:10.1093/eurheartj/ehl141)
Aims The CArdiac REsynchronization-Heart Failure study randomized patients with left ventricular ejection fraction 
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.
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.
Key Words: Heart failure • Dyssynchrony • Randomized controlled trial • Resynchronization • Mortality
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