The authors concluded that the potential role for statin therapy in the prevention of haematological malignancies was not supported with the meta-analysis. Despite some minor limitations, this conclusion appears to reflect the evidence presented and is likely to be reliable.

To determine whether statin therapy may prevent haematological malignancies.

MEDLINE and Web of Science were searched from inception to December 2006. Search terms were reported. References from relevant articles were also checked.

Randomised controlled trials (RCTs) and observational studies (case control and cohort) that evaluated exposure to statins and risk of haematological malignancies were eligible for inclusion in the review. Included RCTs were required to compared statin therapy with placebo or no treatment (and have no other differences in intervention between groups), have a minimum duration of three years, have recruited at least 2000 participants and reported incidence of haematological malignancies during the trial. Statin agents included fluvastatin, lovastatin, pravastatin and simvastatin. Where reported, the mean study duration ranged from 5.1 to eight years. Reported outcomes included incidence of haematological malignancies and incidence of lymphoma, leukaemia, myeloma and non-Hodgkin lymphoma.

The authors did not state how papers were selected for the review or how many reviewers performed the selection.

The quality of the included studies was not assessed.

Risk ratios and their 95% confidence intervals were calculated for each RCT, risk estimates that reflected the greatest degree of control for potential confounders were extracted for observational studies (odds ratio for case-control studies and rate ratio for the cohort study). Intention-to-treat analysis was extracted for all RCTs.

Two reviewers independently extracted data from the primary studies and any disagreements were resolved through consensus.

Studies were combined in a meta-analysis using a random-effects model, grouped by study design. Different measures of risk (risk ratios and odds ratios) were considered equivalent in this instance due to the low incidence rate and thus pooled. The summary estimates (relative risks) from the two meta-analyses were compared with a test of interaction (i.e. RCTs versus observational studies). Statistical heterogeneity was assessed using the Cochran's Q test and the I² statistic. Publication bias was assessed using the Begg and Mazumdar adjusted rank correlation test and the Egger regression asymmetry test.

Fourteen studies were included in the review (n=412,053 patients); six randomised, double-blind, placebo-controlled trials (RCTs, n=46,852patients), seven case-control studies (n=30,447 patients), and one cohort study (n=334,754 patients). All the observational studies controlled for potential confounding factors but age was the only variable that all the included studies accounted for). The number of haematological malignancies ranged from 18 to 116 in the RCTs, from 24 to 2,362 in the case-control studies, and was 1,626 in the cohort study.

All studies: Overall, no significant between group difference was found for risk of haematological malignancies (relative risk 0.85%, 95% CI: 0.64 to 1.12); significant statistical heterogeneity was found (χ² test, p<0.001 and I²=71%). No statistically significant difference between the estimates of statin therapy on incidence of haematological malignancies was found for RCTs and observational studies (z=0.3, p=0.7).

RCTs: When only RCTs were considered, no statistically significant difference between statin therapy and controls was found for risk of haematological malignancies (relative risk 0.92%, 95% CI: 0.72 to 1.16). No evidence of significant statistical heterogeneity was found. Stratifying for type of statin (lipophilic and lipophobic statins) did not significantly alter the results.

Observational studies: When only the observational studies were considered, no statistically significant difference was found between statin therapy and controls (risk ratio 0.83%, 95% CI: 0.53 to 1.29). Evidence of significant statistical heterogeneity was found (χ² test, p<0.001 and I²=82%). Exclusion of the cohort study did not significantly alter the summary effect size or reduce evidence of heterogeneity.

No evidence of publication bias was found using the Begg's test or Egger's test.

A potential role for statin therapy in the prevention of haematological malignancies was not supported with the meta-analysis.

The review question was supported by clear inclusion criteria. The literature search included only two databases. It is not known whether this search was restricted by language, but the authors did assess the likelihood of publication bias. Methods for data extraction were likely to minimise the possibility of reviewer error or bias, but the authors did not report whether similar methods were used for study selection. Whilst the quality of the included studies was not formally assessed, limiting interpretation of the results, only randomised, double-blind placebo controlled trials were included in the RCT group analysis. Greater reported study detail (population and intervention) might have been useful in order to better assess generalisability of the results. Standard meta-analytic methods were used and some attempt was made to investigate potential sources of heterogeneity. Overall, despite some limitations, the authors' conclusion appears to reflect the evidence presented and is likely to be reliable.

Practice: The authors stated that physicians need to be vigilant in ensuring that the use of statins remains restricted to the approved indications.

Research: The authors recommended extended follow-up of statin use to provide further data on long-term effects.

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.