A recent meta-analysis, published in JAMA, has suggested an increase in the risk of developing diabetes with high-dose statin therapy compared with moderate-dose therapy. However, the cardiovascular benefits appear to outweigh the risk of diabetes.

The researchers analysed large, randomised controlled, hard end point studies that compared intensive with moderate-dose statin therapy and included more than 1,000 patients followed up for longer than a year.

The trials studied in the meta-analysis were PROVE IT-TIMI 22, A to Z, TNT, IDEAL, and SEARCH. These five trials included 32,752 patients without diabetes mellitus at baseline.

The results showed that 1,449 patients treated with high-dose statin therapy developed diabetes compared with 1,300 patients on moderate-dose statin therapy. This translated into two additional cases of diabetes mellitus per 1,000 patient-years. The odds ratio for new onset diabetes was 1.12 (95% CI: 1.04-1.22).

Furthermore, higher-dose statin therapy was associated with a reduction in cardiovascular morbidity and mortality compared with moderate-dose therapy. Overall, 3,134 patients treated with high-dose statin therapy and 3,550 patients treated with moderate-dose therapy had a cardiovascular event which equates to 6.5 fewer cases per 1,000 patient-years in the high-dose statin arm, a relative reduction of 16%.

Atorvastatin 80 mg and simvastatin 80 mg were both associated with similar risks of diabetes but atorvastatin was significantly better at reducing cardiovascular events (22% vs 5% risk reduction).

To put these results into perspective, the authors report that the number of patients needed to treat with high-dose statin therapy to prevent one cardiovascular event was 155 and the number needed to treat to cause one case of new onset diabetes mellitus was 498.

Therefore, this meta-analysis highlights a potential risk of high-dose statin therapy but the beneficial effect on cardiovascular outcomes clearly outweighs the increased risk of diabetes. The authors also point out that there is no proposed mechanism to account for this increased risk and that despite this the reduction in cardiovascular morbidity and mortality is maintained.

From a practice perspective, I do not think this study should discourage clinicians from using high-dose statins where clinically indicated and such patients are likely to be screened for diabetes on a fairly regular basis in any case.

Dr Peter Savill