ArticlesCardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial
Introduction
Statin therapy effectively reduces cardiovascular events. Yet, trial data1 and meta-analyses2, 3, 4 suggest that statins also confer increased risk of development of diabetes. In particular, recent overviews show that all statin agents are associated with a small increase in risk of incident type 2 diabetes (hazard ratio [HR] 1·09, 95% CI 1·02–1·17),3 and that intensive doses might be associated with higher risk than are lower doses (HR 1·12, 95% CI 1·04–1·22).4 For these reasons, on March 1, 2012, the US Food and Drug Administration added a warning about diabetes risk to the labels of all statin agents,5 and similar concern has been raised by European drug authorities. These regulatory changes have engendered controversy in the lay and medical press as to whether the cardiovascular benefit of treatment with statins exceeds the diabetes risk, particularly in primary prevention, a setting in which these agents have seen increasing use. The JUPITER (Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin)1 trial provided a contemporary opportunity to address this issue directly.
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Participants and procedures
JUPITER was a randomised, double-blind, placebo-controlled trial designed to investigate whether rosuvastatin 20 mg daily compared with placebo would decrease the rate of first-ever cardiovascular events in 17 802 apparently healthy men and women with LDL cholesterol lower than 3·37 mmol/L (130 mg/dL) and high-sensitivity C-reactive protein (hsCRP) 2 mg/L or higher.1, 6 An important prespecified secondary aim of the trial was to address the effects of rosuvastatin on incident type 2 diabetes;
Results
Of 17 802 JUPITER trial participants, 121 (1%) were missing data for at least one risk factor for diabetes and 78 (<1%) were found at randomisation to have fasting glucose 6·99 mmol/L or greater or clinical diabetes. The remaining 17 603 trial participants (99%) had complete data and were included in this analysis. By comparison with trial participants with no major diabetes risk factors (n=6095), those with one or more major diabetes risk factor (n=11 508) were more likely to be female, have
Discussion
Although JUPITER was the first placebo-controlled statin trial to formally report an increased risk of developing diabetes,1 post-hoc evaluations of previously completed trials showed that this small increase in risk is present for all statins and might relate to drug potency (panel).2, 3, 4 In secondary prevention in high-risk patients with established coronary artery disease, the diabetes risk associated with statin therapy is low in absolute terms when compared with the reduction in
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