Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials

Abstract

on behalf of the investigators of the AVID, CASH and CIDS studies Aims Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia. Methods and ResultsIndividual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect metaanalysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0·306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0·72 (95% confidence interval 0·60, 0·87; P=0·0006). For the outcome of arrhythmic death, the hazard ratio was 0·50 (95% confidence interval 0·37, 0·67; P<0·0001). Survival was extended by a mean of 4·4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction c35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the nonthoracotomy era. ConclusionResults from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.

Long-Term Comparison of the Implantable Cardioverter Defibrillator Versus Amiodarone

“…Several randomized clinical trials [1][2][3][4] provided evidence of increased survival in patients with resuscitated VT/VF who received an ICD compared with those who were treated with amiodarone. However, only the AVID study demonstrated a statistically significant mortality benefit of the ICD over amiodarone.…”

“…For example, patients with an ejection fraction Ͼ35% in subgroup analysis appear to derive little or no benefit from the ICD over amiodarone in these trials. [1][2][3][4] In CIDS, younger patients with better NYHA functional class also appear to derive less benefit (over the time frame studied) from the ICD. 6 At the conclusion of CIDS, the steering committee made no formal recommendations regarding ongoing management of the patients assigned to amiodarone.…”

Implantable Cardioverter‐Defibrillators for Secondary Prevention of Sudden Cardiac Death: A Review

“…For example, patients with advanced NYHA Class symptoms are associated with higher risk of death related to progressive heart failure, which potentially reduces the impact of ICD therapy. As noted previously, in a meta‐analysis of the secondary prevention RCTs, patients with LVEF ≥35% had significantly less benefit compared with those whose LVEF was severely reduced 36. Two such groups of patients who require special consideration are the elderly and those with chronic kidney disease.…”

“…The first found significant reductions in deaths from all causes (HR 0.72; 95%CI 0.60‐0.87) and arrhythmia (HR 0.50; 95%CI 0.36‐0.67) with the ICD vs amiodarone 36, 37. There was no significant difference in nonarrhythmic death (HR 0.93; 95%CI 0.73‐1.17).…”

Multistate 5‐Year Initiative to Improve Care for Out‐of‐Hospital Cardiac Arrest: Primary Results From the HeartRescue Project

“…Similarly, implantable‐cardioverter defibrillator implantation in the Utstein subgroup remained stable over time. Although revascularization is recommended for OHCA patients with ST‐segment–elevation myocardial infarction and predischarge implantable‐cardioverter defibrillator implantation is recommended in clinically appropriate patients, the present data set does not permit the adjudication of the appropriateness of these procedures 31, 32, 33…”