INFORMAÇÃO MÉDICA...(Actualização)

LIPID/METABOLIC
High-dose statin therapy increases the risk of diabetes: Meta-analysis
JUNE 21, 2011 | Michael O'Riordan
London, UK - A meta-analysis of some of the more high-profile statin trials testing the effectiveness of high-dose therapy has revealed a significant increase in the risk of diabetes mellitus associated with statin use in high doses [1]. Compared with moderate-dose therapy across five statin trials, investigators report that treatment with high-dose statins increased the risk of diabetes by 12%.

Senior investigator Dr Kausik Ray (St George's University of London, UK) said that while there might be consequences from the raised blood glucose levels, researchers do not yet know what these long-term effects mean. The net benefit of high-dose statin therapy "is definitely in favor" of using the drugs, he said.

"One thing we do know is that there does appear to be a dose effect with statin therapy, with the risk of diabetes mellitus increasing with higher doses," Ray told heartwire. "Statins have multiple effects and cause a number of changes. What we're seeing is probably an off-target effect, and right now we have no obvious mechanisms. However, lowering LDL-cholesterol levels is probably more important than the increase in blood-sugar levels."

In their analysis, the number of patients needed to treat with high-dose statin therapy to prevent one cardiovascular event was 155, whereas the number needed to treat to cause one case of new-onset diabetes mellitus was 498. Overall, high-dose statin therapy reduced the risk of cardiovascular events in their meta-analysis by 16% compared with low- or moderate-dose statin therapy.

The results of the study are published in the June 22, 2011 issue of the Journal of the American Medical Association.


Previous observed diabetes risk

Speaking with heartwire, Ray said that the idea for the meta-analysis began two years ago, when the signal for diabetes risk was observed in Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER). The group later performed an analysis of some of the early statin trials comparing the lipid-lowering drugs with placebo in 90 000 individuals and observed a significant 9% increase in the risk of diabetes mellitus. That study was reported in the Lancet in 2010 [2].

In this newest analysis, the researchers included large, randomized, controlled, hard-end-point studies that compared intensive-dose statin therapy with moderate-dose statin therapy followed for more than one year. The trials included in the meta-analysis were PROVE-IT, A to Z, TNT, IDEAL, and SEARCH, five trials that together included 32 752 patients without diabetes mellitus at baseline.

"We wanted to look at the different studies comparing the intensity of statin treatment," said Ray. "If the diabetes finding was a real finding, we would expect to see it in the statin trials that tested different intensities of treatment in about 33 000 subjects. The trials all ranged from two to five years in duration, and we had information from five trials comparing high versus low/moderate treatment doses. Our results support our initial findings. We observed a 12% increase in risk for those patients treated with high-dose statin therapy."

In total, 1449 patients treated with high-dose statin therapy developed diabetes compared with 1300 patients assigned to moderate-dose statin therapy. This translated into two additional cases of diabetes mellitus per 1000 patient-years. The odds ratio for new-onset diabetes was 1.12 (95% CI 1.04-1.22). Regarding benefit, 3134 patients treated with high-dose statin therapy and 3550 patients treated with moderate-dose therapy had a cardiovascular event, translating into 6.5 fewer outcomes per 1000 patient-years in the high-dose statin arm, or a relative reduction of 16%.

The investigators did observe differential effects with the different drugs. Whereas atorvastatin 80 mg and simvastatin 80 mg were both associated with similar risks of diabetes mellitus, the benefit differed significantly, with evidence in favor of atorvastatin (22% vs 5% risk reduction for cardiovascular events). The data, said Ray, support the recent Food and Drug Administration (FDA) decision to warn physicians to not start new patients on simvastatin 80 mg and to be vigilant to the risks of muscle toxicity caused by the drug in those who are still taking it.