Implantable cardioverter-defibrillators reduced mortality in patients resuscitated from ventricular arrhythmias
ACP J Club. 1998 May-June;128:60. doi:10.7326/ACPJC-1998-128-3-060
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Antiarrhythmics Versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997 Nov 27;337:1576-83.
To compare the efficacy of an implantable cardioverter-defibrillator (ICD) with antiarrhythmic drug therapy for all-cause mortality in patients resuscitated from near-fatal ventricular fibrillation or who had symptomatic, sustained ventricular tachycardia (VT) with hemodynamic compromise.
Randomized trial with a mean follow-up of 18 months and scheduled interim analyses (Antiarrhythmics Versus Implantable Defibrillators [AVID] study).
56 U.S. and Canadian clinical centers.
1016 patients (mean age 65 y, 79% men, 86% white, 56% with VT, and 45% with ventricular fibrillation at randomization) who were resuscitated from near-fatal ventricular fibrillation, had sustained VT with syncope, or had sustained VT with an ejection fraction of ≤ 0.40 and hemodynamic compromise caused by the arrhythmia. All patients had to be eligible for treatment with amiodarone. Patients who had had revascularization were eligible if their ejection fraction was ≤ 0.40. Follow-up was 99.7%.
507 patients were allocated to an ICD and 509 to antiarrhythmic drug therapy. In the drug therapy group, 356 patients were given amiodarone immediately and the 153 patients who were also eligible for sotalol were randomly allocated to amiodarone (n = 79) or to sotalol (n = 74).
Main outcome measure
Analysis was by intention to treat. The study was stopped early because improved survival in the ICD group was found during a scheduled interim analysis. The ICD group had lower all-cause mortality than the drug therapy group (P < 0.02) (Table) and a lower risk for hospitalization (P = 0.04). Adjustment for baseline risk factors did not change the results. Serious side effects were rare in both groups.
An implantable cardioverter-defibrillator resulted in lower mortality than antiarrhythmic drug therapy among patients resuscitated from ventricular fibrillation or symptomatic, sustained ventricular tachycardia with hemodynamic compromise.
Source of funding: National Heart, Lung, and Blood Institute.
For article reprint: The AVID Clinical Trial Center, 1107 N.E. 45th Street, Room 505, Seattle, WA 98105, USA. FAX 403-283-5594.
Table. Cardioverter-defibrillator vs antiarrhythmic drug therapy*
|Outcome||Defibrillator EER||Drug CER||RRR (95% CI)||ARR |EER-CER|||NNT (CI)|
|All-cause mortality||16%||24%||34% (15 to 49)||8%||13 (8 to 30)|
*Abbreviations defined in Glossary; RRR, ARR, NNT, and CI calculated from data in article.
The AVID study provides the first published results of a randomized clinical trial comparing ICD with the best available anti-arrhythmic drug therapy for patients who had ventricular fibrillation or symptomatic sustained VT. All-cause mortality was 39% less at 1 year, and the benefit persisted at 2 and 3 years. Minor reservations about the validity of the results may be raised because the ICD group had a lower prevalence of congestive heart failure at baseline and used more β-blockers, but adjusted analyses did not significantly change the outcomes. No standard loading regimen was set for amiodarone, and the dose at 2 and 3 years is rather conservative for such a high-risk population. Nevertheless, the evidence for reduced mortality with the ICD was strong. Serious side effects were relatively rare with both ICD (occurring mainly in association with implantation) and amiodarone. Very few patients were randomly allocated to sotalol.
Among patients who have had life-threatening arrhythmias, the ICD seems to provide longer survival than empiric amiodarone. Is ICD therapy affordable? Cost-effectiveness studies are rare, but early studies indicate costs in the range of U.S. $115 000/life-year saved (1)—a range considered to be problematic even for a wealthy society. However, only relatively short follow-up is available in the AVID study and the survival curves do not seem to be converging. With improving technology, longer battery life, and decreasing costs, the cost-benefit analysis may eventually become more favorable.
The CABG Patch Trial compared the ICD with a no-defibrillator control in a population of patients who were having CABG, who had depressed ejection fraction, and who had an abnormal electrocardiogram, placing them at substantial risk for arrhythmic death. After a mean follow-up of 32 months, all-cause mortality rates in the 2 groups were virtually identical and were unchanged by adjustment for prespecified covariants. The use of cardiac drugs, including antiarrhythmic drugs and β-blockers, was similar in the 2 groups.
The Multicenter Automatic Defibrillator Implantation Trial (MADIT) (2) enrolled patients with nonsustained VT, low ejection fraction, and nonsuppressible VT on electrophysiologic testing. The patients had a surprisingly high mortality rate that was greatly reduced by the ICD.
For the CABG Patch Trial, it seems that the deaths of the persons were less able to be prevented by the ICD than were those of patients in the AVID trial and MADIT. Although the revascularization may have decreased the risk for ischemia-predicted arrhythmias, the rate of ICD discharge was relatively high and similar to that in MADIT, an observation that is difficult to explain if fewer potentially lethal arrhythmias were present. Data on the cause of death and from the stored electrocardiograms (available only in the latter part of the study) may help to clarify this possibility.
For now, which patients should receive an ICD? Those who have had ventricular fibrillation or sustained symptomatic VT (the AVID population) should receive an ICD, provided that arrhythmias do not recur frequently and that patients are free of severe uncontrolled ischemic heart disease or congestive heart failure and other illnesses associated with a high risk for short-term mortality. Every effort should be made to optimize medical therapy, especially the management of myocardial ischemia and congestive heart failure. Although the cost per life-year saved is high, the therapy is substantially more effective than optimal antiarrhythmic drug therapy and the cost is likely to decrease. Although the MADIT patients with nonsustained VT, nonsuppressible VT, and low ejection fraction benefited from the ICD, using this treatment is likely to be very costly. In addition, the results of a single small trial are, in my opinion, insufficient to justify this approach over medical therapies for now. Further data from studies, such as MADIT II, may provide clearer therapeutic directions. Patients with a low ejection fraction and other predictors of risk for life-threatening arrhythmias but no VT or symptomatic ventricular arrhythmia do not seem to benefit from ICD implantation.
John A. Cairns, MD
University of British ColumbiaVancouver, British Columbia, Canada
John A. Cairns, MD
University of British Columbia
Vancouver, British Columbia, Canada
1. Larsen GC, McAulty JH, Hallstrom A, et al. Hospitalization changes in the antiarrhythmics versus implantable defibrillators (AVID) trial: the AVID economic analysis study [Abstr]. Circulation. 1997;96:1-77.