The review concluded that implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death did not reduce all-cause mortality in women with advanced heart failure. Some methodological limitations of the review should be taken into account when interpreting the authors' conclusions, but their recommendation for further research in women appears reasonable.

To assess the effectiveness of implantable cardioverter-defibrillators as primary prevention to reduce mortality in women with advanced heart failure.

MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to 2008 with no language restrictions. Search terms were reported. The National Institutes of Health ClinicalTrials.gov and the Food and Drug Administration websites were also searched. Scientific meetings of the American College of Cardiology, the American Heart Association, the European Society of Cardiology, and the North American Society of Pacing and Electrophysiology/Heart Rhythm Society were scanned between 1994 and 2008. Bibliographies of recent narrative reviews were handsearched.

Randomised controlled trials (RCTs) assessing implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death in patients with heart failure and reduced left ventricular ejection fraction, were eligible for inclusion. Eligible trials were required to report all-cause mortality in the female population as the primary or secondary outcome.

Included trials compared implantable cardioverter-defibrillators with pharmacologic therapy, amiodarone hydrochloride or placebo. The mean age of patients ranged from 58.3 to 66.5 years. Between 13.2% and 30.0% of patients were identified as New York Heart Association class III/IV. Some patients had non ischaemic cardiomyopathy and the majority of patients were receiving medication at baseline. The mean duration of congestive heart failure ranged from less than 30 days up to 2.8 years.

The authors did not state how the papers were screened for inclusion.

Two independent reviewers assessed the quality of the included trials using the 5 point Jadad scale, including items on follow-up, crossover, withdrawals/dropouts and intention-to-treat analyses. Disagreements were resolved through referral to a third reviewer.

Two independent reviewers extracted outcome data to calculate hazard ratios and their 95% confidence intervals. Disagreements were resolved through referral to a third reviewer.

Hazard ratios were pooled using a fixed-effect model, or a random-effects model where statistical heterogeneity was evident, weighted by the inverse of the variance. Statistical heterogeneity was assessed using Cochran's Q and the I² test. Sensitivity analyses were carried out by excluding each trial in turn. Publication bias was assessed using the Begg test and funnel plots.

Five randomised controlled trials (RCTs) were included in the review (n=4,744 patients; n=934 women). Sample sizes ranged between 458 and 1,676 patients. All RCTs scored 4 according to the Jadad scale. Between 0% and 13% of patients were crossed over to implantable cardioverter-defibrillators, and between 1.7% and 19.5% were crossed over to pharmacologic therapy. All RCTs received some funding from the device manufacturer.

There were no significant differences in mortality rates between women receiving implantable cardioverter-defibrillators versus medical therapy. There was no evidence of significant statistical heterogeneity; sensitivity analyses did not significantly alter the results. By comparison, mortality rates were significantly reduced in males receiving implantable cardioverter-defibrillators compared with those receiving medical therapy, hazard ratio 0.78 (95% confidence interval: 0.70 to 0.87).

There was no evidence of significant publication bias.

Implantable cardioverter-defibrillators for the primary prevention of sudden cardiac death did not reduce all-cause mortality in women. However, further research is needed to identify the population of women who may benefit the most from this intervention.

The review answered a clearly defined question and was supported by appropriate inclusion criteria. A comprehensive literature search was undertaken with no language restrictions, which reduces the potential for language bias. Unpublished data were not sought, which means that relevant papers may have been missed. However, publication bias was assessed and no evidence of bias was found. Validity was assessed using a reliable tool, and all included trials were comparable in quality. Steps were taken to reduce reviewer error and bias during validity assessment and data extraction through duplication. The same was not true for study selection, which means that reviewer error and bias cannot be ruled out completely. Appropriate methods appear to have been used to combine the trials and assess statistical heterogeneity. However, it was not possible to identify potential differences in baseline characteristics of the women, so it was unclear whether the female population was comparable. These considerations should be taken into account when interpreting the authors' conclusions, but their recommendation for further research in women appears reasonable.

Practice: The authors stated that implantable cardioverter-defibrillators can affect mortality by preventing deaths caused by malignant arrhythmias. However, arrhythmic death was not the main end-point for women in many of the included studies.

Research: The authors stated that a larger clinical trial, preferably using individual patient data, is required to target women with heart failure. Further research is also warranted to investigate whether implantable cardioverter-defibrillators reduce arrhythmic death among women with heart failure. Future research should also take into account economic and social factors to determine the cost-effectiveness of this therapy in women.

Not stated.

Hernandez AF, Fonarow GC, Liang L, et al. Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure. JAMA. 2007;298:1525-32.

Curtis LH, Al-Khatib SM, et al. Sex differences in the use of implantable cardioverter-defibrillators for primary and secondary prevention of sudden cardiac death. JAMA. 2007;298:1517-24.

Redberg RF. Disparities in use of implantable cardioverter-defibrillators: moving beyond process measures to outcomes data. JAMA. 2007;298:1564-6.

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.