The authors concluded that women enrolled in primary prevention implantable cardioverter-defibrillator (ICD) trials had the same mortality as men while experiencing significantly less appropriate ICD intervention. Evidence appeared to support the authors’ conclusions, but lack of reporting of review methods and study quality made it difficult to assess the reliability.

To evaluate the benefits of primary prevention implantable cardioverter-defibrillator (ICD) in women with left ventricular dysfunction.

PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), BioMed Central, Cardiosource, ClinicalTrials.gov and Web of Science were searched for published studies up to October 2009. No language restrictions were applied. Search terms were reported. Proceedings from the last five years of annual conferences of five specified relevant societies were screened and three relevant specified websites were examined for oral presentations and/or expert slide presentations.

Randomised controlled trials (RCTs) were eligible if they compared ICD therapy with placebo in patients with dilated cardiomyopathy and who had no history of major arrhythmic events and presented risks of specified outcomes for women compared to men. Studies had to adjust risk statistics for all possible baseline confounders or covariates. Review outcomes were total mortality, appropriate ICD intervention (defined as intervention on rapid sustained ventricular tachycardia or fibrillation) and survival of ICD compared to placebo.

Most patients had dilated cardiomyopathy of ischaemic aetiology. Some studies only included patients with nonischaemic cardiomyopathy. Most studies included patients with a previous myocardial infarction. The proportion of women was 24%. Mean left ventricular ejaculation fraction was 24% and in most studies this was similar for men and women. Seventy-four per cent of patients had cardiomyopathy of an ischaemic aetiology. Where reported, the percentage of patients with New York Heart Association functional class greater than II ranged from 20% to 70% and tended to be higher among women than men.

Two reviewers independently conducted searches; no other details of the study selection process were reported.

The authors stated that study quality was assessed using the risk of bias (selection, performance, detection and attrition).

The authors did not state how many reviewers assessed validity.

Logarithmic hazard ratios (HR) and standard errors were extracted from each study.

The authors did not state how many reviewers extracted data.

Pooled hazard ratios and 95% confidence intervals (CI) were calculated using a DerSimonian and Laird random-effects model.

For studies that directly compared total mortality and appropriate ICD therapy between men and women, HRs were adjusted for the maximum number of confounders and covariates and entered into multiple Cox regression analysis.

For the analysis of ICD survival benefit where there was no direct comparison between men and women, meta-regression within each gender was used to examine the influence of the potential confounders that were not accounted for in the primary studies: age, aetiology of cardiomyopathy, New York Heart Association functional class, left ventricular ejection fraction, race, baseline drug therapy and length of study follow-up.

Sensitivity analysis was conducted using a fixed-effect model and after excluding: each study in turn; studies that involved only ischaemic dilated cardiomyopathy patients; studies that involved a mix of ischaemic and nonischaemic patients; and the study that involved only nonischaemic patients.

Heterogeneity was assessed using the Cochrane Q statistic and the I² statistic. The possibility of publication bias was explored using a funnel plot and Egger’s test.

Five RCTs were included (n=7,229 patients). Follow-up ranged from 16 to 45 months in tables and 24 to 60 months in the text.

Total mortality: There was no statistically significant difference between men and women in total mortality (four studies). Significant heterogeneity was found (I²=80%). Results were similar for the fixed-effect model and sensitivity analyses. There was no evidence of publication bias from the funnel plot or Egger’s test.

Appropriate ICD intervention: The rate of appropriate ICD intervention was significantly lower in women (HR 0.63, 95% CI 0.49 to 0.82; I²=0%). Results were similar after sensitivity analyses. There was no evidence of publication bias from the funnel plot or Egger’s test.

ICD survival benefit: Compared with placebo, prophylactic ICD therapy was associated with a significant reduction in total mortality among men (HR 0.67, 95% CI 0.58 to 0.78; I²=0%) and a smaller non-significant reduction in women (four studies, I²=0%). Results were similar after sensitivity analyses. Meta-regression showed no significant interactions between variables and mortality.

Women enrolled in primary prevention ICD trials had the same mortality as men while experiencing significantly less appropriate ICD intervention. This suggested a smaller impact of sudden cardiac death on overall mortality in women with dilated cardiomyopathy. The findings may explain the smaller ICD survival benefit among women.

The review question was clearly stated and inclusion criteria were appropriately defined. Several relevant sources were searched. Attempts were made to minimise language bias. Potential sources of unpublished studies were searched. No evidence of publication bias was found, but the small number of studies may have limited the value of these tests. The authors stated that they assessed validity, but did not report their results and so these studies and any synthesis from their data may not have been reliable. Methods used to select studies were not completely described and methods used to assess validity and extract data were not described. Therefore, any efforts made to reduce reviewer errors and bias were unknown.

Studies were pooled using meta-analysis. Heterogeneity was assessed. The influence of various potential confounders was examined. Differences between studies were discussed.

Evidence appeared to support the authors’ conclusions, but lack of reporting of review methods and study quality made it difficult to assess the reliability.

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

Research: The authors stated that further research was required to determine the cost-effectiveness of primary prevention ICD therapy in women.

Not stated.

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.