The review suggested an association between the use of statins and a reduction in the ventricular tachycardia/ventricular fibrillation occurrence in recipients of implantable cardioverter-defibrillators, mainly in patients with ischaemic cardiomyopathy. The restricted study design reviewed, coupled with significant variation across studies, means the clinical relevance and reliability of the authors' conclusions is uncertain.

To assess whether statin therapy was associated with a decrease in the incidence or recurrence of ventricular tachycardia/ventricular fibrillation in patients with an implantable cardioverter-defibrillator.

MEDLINE and The Cochrane Library were searched from 1980 up to July 2009 for studies in English published in peer-reviewed journals; search terms were reported. Bibliographies of retrieved articles were scanned. Abstracts presented at the American Heart Association, American College of Cardiology, and Heart Rhythm meetings from 2000 to 2008 were also searched.

It appeared that eligible studies had to have a prospective or nested cohort design. To be included, studies had to compare statin treatment with a control group in patients with an implantable cardioverter-defibrillator for primary or secondary prevention. Eligible studies had to recruit at least 50 patients and perform follow-up for at least six months. Studies were required to report the incidence/recurrence of ventricular tachycardia/ventricular fibrillation, confirmed by implantable cardioverter-defibrillator interrogation (the review's primary endpoint), or time to first appropriate shock therapy.

Mean ages of included patients ranged from 59 to 69 years. Over three-quarters of patients were men. In all included studies, the mean ejection fraction was less than 40%. Around two-thirds of patients used beta-blockers and angiotensin-converting enzyme inhibitors.

The authors did not state how many reviewers selected studies.

Study quality was assessed using the Newcastle Ottawa scale; studies that scored 8 or 9 points (out of a maximum score of 9) were considered good quality. Authors were contacted for missing information when necessary.

It appeared that two reviewers independently performed the quality assessment with disagreements resolved by a third reviewer.

Data were extracted to calculate odds ratios (OR) with 95% confidence intervals (CI).

Two reviewers independently extracted data, with disagreements resolved by a third reviewer.

Meta-analyses were performed to calculate pooled odds ratios with 95% confidence intervals. A random-effects model was used when heterogeneity was high (Ι² values higher than 50%), otherwise a fixed-effect model was used.

A subgroup analysis examined results in studies of patients with coronary artery disease but not non-ischaemic cardiomyopathy. A sensitivity analysis explored the effect of using studies that scored at least 8 points on the Newcastle Ottawa Scale. The effect of single study exclusion on results was assessed. Meta-regression analyses were used to explore the effect of study characteristics.

Publication bias was assessed using a funnel plot and the Egger weighted regression test.

Four prospective cohort studies and three nested cohort studies were included in the review (2,778 patients, range 78 to 1,204). One study scored 6 points on the Newcastle Ottawa scale, one scored 7, and five scored 8. The mean follow-up period was 19.7 months (range 10.2 to 31 months).

Patients on statin therapy were associated with a reduction in the risk of developing ventricular tachycardia/ventricular fibrillation compared with patients not taking a statin (OR 0.55, 95% CI 0.34 to 0.90; seven studies; Ι²=81%); the absolute risk reduction was 12.5%. There was no evidence of publication bias.

Meta-regression showed no statistically significant relationship with mean follow-up time, age, ejection fraction or year of publication. In a subgroup analysis, there was a significant risk reduction in patients with ischaemic cardiomyopathy (OR 0.46, 95% CI 0.22 to 0.99; five studies; Ι²=87%). In the sensitivity analysis of studies of higher methodological quality, a significant risk reduction was also seen (OR 0.48, 95% CI 0.27 to 0.86; five studies; Ι²=84%).

The meta-analysis results suggested an association between the use of statins and a reduction in the ventricular tachycardia/ventricular fibrillation occurrence in recipients of implantable cardioverter-defibrillators, mainly in patients with ischaemic cardiomyopathy.

The review addressed a clear question, but the rationale for not including other study designs, including randomised trials, was not made clear. The authors noted in their discussion that one key randomised trial had been conducted in this area; given the authors' first inclusion criterion (analysis comparing statin therapy intervention with a control group), it was unclear why this trial was not included. Attempts to identify relevant studies were undertaken by searching two electronic databases and conference abstracts, although the restriction to included only studies in English published in peer-reviewed journals meant that some relevant studies may have been missed. Suitable methods were employed to reduce the risks of reviewer error and bias during data extraction and quality assessment, although it was unclear whether such methods were used during study selection.

Study quality was assessed and was used in interpreting the results of the review. Basic study details were provided and appropriate methods were used to pool data and assess heterogeneity. Despite conducting sensitivity and subgroup analyses, all the key results highlighted by the authors were still subject to significant statistical heterogeneity.

The authors noted the limitations associated with the observational study designs included in their review, and their conclusions broadly reflected the evidence presented. However, the restricted study design reviewed, coupled with the significant heterogeneity found, means the clinical relevance and reliability of their conclusions is uncertain.

Practice: The authors speculated that statin use might possibly improve the quality of life of implantable cardioverter-defibrillator recipients and at-risk patients who met criteria for device therapy but could not receive implantable cardioverter-defibrillators for other reasons.

Research: The authors stated a need for further trials in high-risk patients and more studies at a molecular level to examine the pleiotropic effects of statins.

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.