Eleven-year follow-up results show advantage of ICDs over amiodarone in CIDS

Shelley Wood

November 19, 2002

Chicago, IL - An 11-year follow-up of the Canadian Implantable Defibrillator Study (CIDS) suggests that that the benefit of ICD therapy over amiodarone appears to increase over time. The follow-up analysis, evaluating the long-term efficacy and tolerance of amiodarone in ventricular tachycardia/fibrillation (VT/VF) survivors, was presented by Dr Paul Dorian (St Michael's Hospital, Toronto, ON) here at the American Heart Association November 2002 meeting.

"This subset of CIDS demonstrates significant benefit of ICDs increasing over time and that amiodarone as first-line monotherapy for the long-term prevention of sudden cardiac death is not useful," Dorian stated.

The original CIDS compared amiodarone and ICDs in 659 patients followed for a mean of 3 years. A benefit of ICD therapy was seen in patients who were at high risk of death at study onset, but otherwise no statistically significant difference was seen overall in terms of mortality between the amiodarone and ICD groups. Dorian explained to heartwire that existing data have led investigators to suspect that the duration of benefit with ICD therapy may not be that long. "There is weak evidence to suggest that the curves separating amiodarone and ICD therapy may converge at 4 or 5 years, but the truth is, we really don't know." These latest, albeit substudy, results from CIDs are some of the first to address ICD efficacy in the long term, he said.

CIDS subanalysis out to 11 years

The CIDS follow-up analysis was conducted in all of the CIDS participants at a single centerSt Michael's Hospitalfrom the multicenter trial who were randomized to receive amiodarone (n=60) or an ICD (n=60), then followed from 1991 to 2002. Dorian reported that the primary end point of the analysis, all-cause mortality, was higher in the amiodarone arm (28 deaths) than in the ICD patients (16 deaths). These deaths translated into an annual mortality rate of 8.4% in the amiodarone patients, compared with 4.8% in the ICD patients, yielding a hazard ratio of 2.01 (p=0.0231) and suggesting that the survival curves separating amiodarone and ICDs actually continue to diverge, at least out to 11 years. Presumed arrhythmic death was the predominant cause of mortality.

An analysis of side effects in the amiodarone patients showed that 82% experienced side effects of some kind, and half had "significant" side effects necessitating a lower dose or cessation of therapy. Kaplan-Meier analyses of the data projected that any patient undergoing amiodarone therapy would experience a significant side effect, arrhythmic event, or death after 8 years on the drug.

Ethical considerations and the medicolegal environment

During the question period, Dr Douglas P Zipes (Krannert Institute of Cardiology, Indianapolis, IN) asked whether Dorian and his colleagues had had any ethical concerns about keeping patients on amiodarone, in light of data that has emerged since CIDS formally ended. In the interim, the AVID, MADIT, and MUSTT trials have all shown a benefit of ICDs over antiarrhythmic drugs for the prevention of sudden death.

Dorian responded that the St Michael's investigators had had "extensive discussions" about their plan to continue the analysis, deciding ultimately to leave the decision in the hands of individual treating physicians. Dorian noted that, at the time, CIDS had shown no advantage to ICDs over amiodarone, so the initial decision to continue follow-up was more straightforward. As an additional factor, resource constraints in Canada make it impossible for all patients with current indications for an ICD to receive one; hence, Dorian et al made the decision to "save" ICDs for patients presenting for the first time with an ICD indication.

To heartwire , Dorian elaborated: "At the time that we were discussing continuing CIDS, the patients on amiodarone appeared to be doing well and we saw no compelling reason to stop or that the benefit of the drug would be lost. It's always easier to keep a patient on an existing therapy than to switch them to a new one."

Canada, Dorian added, has a very different medicolegal climate from the US, as well. "However, it's fair to say now that our approach was incorrect, but at the time it was a considered decision."

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