Does pravastatin promote cancer in elderly patients ?

[HMG–CoA] reductase inhibitors) are widely used in the treatment of lipid disorders, especially hypercholesterolemia. Clinical trials have shown that statins are beneficial in both primary and secondary prevention of coronary and cerebrovascular disease events. Statins reduce cholesterol levels by inhibiting HMG–CoA reductase, the enzyme responsible for converting HMG–CoA to mevalonate (a cholesterol precursor). In addition, statins improve endothelial function, stabilize plaques, reduce free radical formation and attenuate the extent of endothelial inflammation, thus providing other potential benefits for patients regardless of their cholesterol level. However, in 2002 the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial reported an increase in cancer rates among study participants assigned to hydrophilic pravastatin. This trial, which is the only randomized placebocontrolled trial to evaluate pravastatin in a unique population of elderly patients, showed that the reduced number of deaths from coronary artery disease was associated with an increased number of cancer-related deaths. The authors suggested that the increased cancer rate was most likely due to chance. However, a significant increase in cancer rates among elderly patients assigned to pravastatin therapy was also reported in a subgroup analysis of the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial. In contrast, several randomized controlled trials of lipophilic statin therapy have not reported an increased risk of cancer. The aim of our study was to assess the effect of pravastatin therapy on cancer risk and to examine whether the effect varies according to age by conducting a detailed metaanalysis and meta-regression analysis of randomized controlled trials published in the peer-reviewed literature.