According to the results of a systematic review and meta-analysis published early online in the British Medical Journal (BMJ), findings from placebo-controlled statin trials do not support the hypothesis that statins reduce the risk of infections.
The authors note that statins are known to have anti-inflammatory and immunomodulatory properties, in addition to their cholesterol-lowering effects; these may be beneficial in the management of infection. Although population-based studies over the past few years have reported associations between statin use and a reduced risk of infectious outcomes, there are potential biases and confounders at play and the association is therefore inconclusive.
The purpose of the current study was to determine whether the beneficial association between statins and infections seen in observational studies is causal. The authors hypothesised that if such an effect exists, it would be possible to detect it in the results of large randomised, placebo-controlled studies. They therefore carried out a systematic review of the literature (Medline in PubMed, Embase, and the Cochrane central register of controlled trials; to March 2011) to identify such studies, and included those enrolling a minimum of 100 participants, with follow-up for at least one year, that reported infection or infection related death and were published in English. After screening, a total of 11 studies (n=30,947; 45.6% received statin therapy and 54.4% received placebo) were included in the analysis, with an average follow-up of 3.3 (range 1-5.1) years.
The authors report that 4,655 of the study participants (2,368 randomised to statins and 2,287 to placebo) reported an infection during treatment. Meta-analysis showed no effect of statins on the risk of infections (relative risk 1.00, 95% CI 0.96 to 1.05; p=0.93) or on infection related mortality (0.97, 0.83 to 1.13; p=0.71). The included studies showed low heterogeneity and the exclusion of data from one study that lacked double-blinding did not significantly alter the results.
The authors compare their results with those from other studies and note some of the limitations of their analysis, for example the inclusion of only 11 studies precluded the conduct of subgroup analyses for statin dose, type, patient characteristics and type of infection. There was also no information on the validity of the infectious outcomes, although the authors say that they would expect these events to be noticed and reported.
The authors conclude that their analysis provides no evidence to support the hypothesis that statin use decreases the risk of infections. They say this weakens any argument for conducting a randomised controlled trial of statins for infection prevention, and suggest that a better approach would be to push reporting of infectious outcomes in detail whenever statin trials are undertaken - this could identify potential subgroups in whom such testing may be more worthwhile.