This review investigated the effectiveness of implantable cardioverter defibrillators (ICDs) in patients with increased risk of sudden cardiac death. The authors concluded that ICDs are more beneficial than drug therapy for secondary prevention of sudden cardiac death and for primary prevention in certain high-risk groups. The conclusions are likely to be reliable.

To assess the efficacy of implantable cardioverter defibrillators (ICDs) in individuals with increased risk for sudden cardiac death.

MEDLINE (1980 to 24 September 2002), the Cochrane Controlled Trials Register (Issue 3, 2002), EMBASE (1980 to 2002), Web of Science, NLM Gateway, Cardiosource, a clinical trials registry, ClinicalTrials.gov, CRISP, the National Research Register, the Glaxo-Wellcome Clinical Trials Register, LILACS, OCLC ProceedingsFirst and NHS EED. All databases were searched on 24 September 2002. Bibliographies of relevant papers were handsearched. Experts, manufacturers and primary authors were contacted for additional trials. Relevant conference proceedings were also searched. The search terms were reported and no language restrictions were applied.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) were eligible for inclusion. Studies in which over 50% patients crossed over to the other treatment group were excluded from the review.

Specific interventions included in the review

Studies of ICDs versus placebo or antiarrhythmic therapy were eligible for inclusion. The ICDs used in the included studies were either transthoracic or transvenous. The control treatments were amiodarone, sotalol, metoprolol, propafenone, antiarrhythmic drugs, no antiarrhythmic therapy and usual care.

Participants included in the review

Studies of individuals with increased risk for sudden cardiac death or ventricular arrhythmia who had evidence of heart failure or coronary artery disease (primary prevention), or survivors of sudden cardiac death or unstable ventricular rhythm (secondary prevention), were eligible for inclusion. Studies of patients with inherited arrhythmic disorders were excluded from the review. Those included were either high- or moderate-risk patients and all (except in one study) had ischaemic heart disease. The majority of the patients were men and the mean age ranged from 52 to 66 years.

Outcomes assessed in the review

Studies that reported the outcomes sudden cardiac death and all-cause mortality were eligible for inclusion.

How were decisions on the relevance of primary studies made?

Two investigators independently reviewed titles and abstracts to determine the relevance of studies. Any disagreements were resolved by consensus.

The validity of the included RCTs was assessed on the basis of blinding, randomisation and allocation concealment. The authors did not state how the papers were assessed for validity, or how many reviewers performed the validity assessment.

Two investigators used standardised data forms to review the full papers. Any disagreements were resolved by consensus. Intention-to-treat data were collected in order to calculate the summary relative risks (RRs) for sudden cardiac death and all-cause mortality. Data on total cardiac mortality, total non-cardiac mortality, concomitant medication and adverse events were also recorded. For several trials the authors referred to secondary publications, or contacted study authors, to determine causes of death.

How were the studies combined?

The studies were combined using a random-effects model (DerSimonian and Laird) and a fixed-effect model (Mantel-Haenszel-Peto). Where there was no difference in the results and no statistical heterogeneity, the results of the fixed-effect model were reported. Publication bias was assessed using a funnel plot.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the Cochran Q-test. Sensitivity analyses were also conducted to assess the potential effect on the results of publication year, study quality and allocation concealment. Subgroup analyses were performed for primary and secondary prevention and (for primary prevention) for high- and moderate-risk patients.

Eight RCTs (n=4,909) were included in the review.

Three of the 8 trials were concerned with secondary prevention and the remaining 5 (3 with high-risk and 2 with moderate-risk patients) were primary prevention. The authors reported that randomisation and allocation concealment were adequate in all trials; blinding was not used in any of the trials.

ICDs were effective in preventing sudden cardiac death (RR 0.43, 95% confidence interval, CI: 0.35, 0.53). This was the case for both primary prevention (RR 0.37, 95% CI: 0.27, 0.50) and secondary prevention (RR 0.50, 95% CI: 0.38, 0.66). There was no significant heterogeneity amongst these trials, nor any difference observed in summary effect estimates for the different types of ICD.

There was an overall beneficial effect of ICDs on all-cause mortality (RR 0.74, 95% CI: 0.67, 0.82). This was the case for both primary prevention (RR 0.72, 95% CI: 0.63, 0.84) and secondary prevention (RR 0.76, 95% CI: 0.65, 0.89). There was significant heterogeneity between primary prevention trials of high-risk and moderate-risk patients for total mortality results (P<0.001). No survival benefit with ICD therapy was observed in moderate-risk patients.

In the 5 trials that reported on total cardiac mortality, the RR was 0.81 (95% CI: 0.69, 0.96). No differences were noted for non-cardiac mortality between patients receiving ICDs and medical treatment alone in the 3 trials that reported on this outcome (RR 0.91, 95% CI: 0.60, 1.38).

Complication rates were higher for transthoracic ICD than for newer ICD models. Further details on adverse events were given in the paper.

Funnel plots did not suggest the presence of publication bias.

ICDs are more beneficial than drug therapy for secondary prevention of sudden cardiac death, and for primary prevention in certain high-risk groups. However, further research is needed to develop accurate risk stratification tools, and to determine the economic and quality-of-life impact of ICD therapy in different patient subgroups.

This review was supported by a clear question and the inclusion criteria were explicit. A comprehensive database search was complemented by a variety of other sources to identify relevant studies, and no language restrictions were applied. Attempts were made to identify unpublished studies. Publication bias was assessed, as were potential sources of heterogeneity between the studies. The meta-analysis for the synthesis of studies measuring sudden cardiac death appeared appropriate and subgroup analyses were reported in detail. Adequate steps were taken to minimise possible biases in most of the review process. The authors' conclusions are likely to be reliable.

Practice: The authors did not state any implications for practice.

Research: The authors stated that further research is needed to develop accurate risk stratification tools, and to determine the economic and quality-of-life impact of ICD therapy in different patient subgroups. More specifically, they recommended a meta-analysis of individual patient data from existing studies and ongoing trials with mortality end points.

This additional published commentary may also be of interest. Newman D. Review: implantable cardioverter defibrillators reduce sudden cardiac death, all-cause mortality, and cardiac mortality. ACP J Club 2003;139:31.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.