Cleland, John (United Kingdom)
see Discussant report
List of Authors:
John GF Cleland, Nick Freemantle, Erland Erdmann, Daniel Gras, Lukas Kappenberger, Luigi Tavazzi, Jean-Claude Daubert
Introduction: The CARE-HF trial, first presented in 2005, established that cardiac resynchronisation therapy (CRT) exerted a striking reduction in mortality in patients with heart failure who had features of dyssynchrony. There are very few long-term followup data in patients with CRT. This is a report on the long-term outcome of patients in the trial. Methods: Enrolment began at the end of 2000 and was complete by March 2003. After reporting the main study results in 2005, investigators were asked to inform patients of the results and implant a CRT device if still appropriate and subsequently asked to consent patients for long-term follow-up until 30th September 2009. Results: Of 813 patients originally enrolled, 343 (42%) died prior to re-consent, 111 patients (14%) were not or could not be contacted, 50 (6%) were alive but declined to participate and 309 (38%) consented to long-term follow-up. Of patients originally assigned to control, most survivors had received CRT by the time of re-consent. From the time of randomization, 222 patients originally assigned to pharmacological therapy and 192 originally assigned to CRT were known to have died. The hazard ratio for mortality in patients originally assigned to CRT compared to those originally assigned to the control group was 0.768 (95% CI 0.633 to 0.931; P = 0.007). No subgroup interactions were observed. Conclusion: The effect of CRT on mortality observed in the randomised phase of CARE-HF persisted during long-term follow-up. Implantation of CRT devices after study completion may have prevented further divergence of the survival curves. The benefit of CRT was observed in patients above and below the median age of 66 years. In patients aged <66 years with moderate to severe heart failure and evidence of cardiac dyssynchrony, CRT would be expected to increase median survival from about 5 years to >8 years. Survival might have been even greater in this group had CRT-defbrillators, rather than CRT-only devices, been used.
Breithardt, Ole A (Germany)
see Presenter abstract
Introduction: Several randomized controlled clinical trials have well established the important role of cardiac resynchronisation therapy (CRT) for selected symptomatic patients with advanced systolic heart failure with cardiac dyssynchrony identified by the presence of a widened QRS complex, typically a left bundle branch block. However, the available information of the key clinical trials is limited to a follow-up duration between one to two years. Thus, it was so far unclear whether the clinical benefit of CRT would persist for a longer period. Small single centre studies have analysed the long-term clinical outcome and patient survival for longer periods, but without a control group for comparison. The CARE-HF study is unique among the major CRT trials as the patients in the active treatment arm received only CRT pacemakers (CRT-P) without defibrillator backup. Furthermore, the CARE-HF trial reported results from a comparatively long average follow-up of 29 months in the main trial and 37 months in the “extension trial”. After termination of the main study, the investigators initiated the CARE-HF Long-Term Follow-Up study (CARE-HF LTFU) and obtained further data on patient survival and device status with an even longer follow-up duration between 6.5 to 9 years. These results were presented by J.G.F. Cleland during the Clinical Trial Update Session. It is important to note that CARE-HF LTFU is not a true randomized trial, but a follow-up registry of patients previously implanted within a randomized trial. After the main study demonstrated a clear survival benefit for the active treatment group (with a CRT-P device), more than 90% of patients from the initially medically treated control group crossed over and had received a CRT device at the time of re-consent for CARE-HF LTFU. Thus, the presented study results do not show the complete survival benefit of CRT in such a typical heart failure population, but rather the effect of delayed CRT implantation. This might be appreciated in the presented survival curves which clearly diverge early during the course of the randomized main study – showing the clear survival benefit for patients with a CRT device. Between 3-6 years, after termination of the main study, most control patients received a CRT device and the curves run parallel. Finally, the survival curves seem to converge again slightly towards the end of the LTFU, possible showing the beneficial effects of delayed CRT implantation. There is no information about the percentage of implanted CRT defibrillators (CRT-D) in the original control group and it can only be speculated that a significant proportion of control patients received a CRT-D device, which might provide some additional survival benefit. Conclusion: A clear conclusion from CARE-HF LTFU is that delayed CRT implantation is associated with a persistent reduction in overall survival. Based on this information, delaying CRT implantation in eligible patients - based on the inclusion criteria of the CARE-HF main study - can not be justified. The median survival of more than 7 years for patients with advanced heart failure, dyssynchrony and an age of less than 66 years treated with a CRT-P device without defibrillator backup is remarkable.
711003 - 711004
Clinical Trial Update III
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