Cardiovascular Benefits and Diabetes Risks of Statin Therapy in Primary Prevention: An Analysis From the JUPITER Trial

Study Questions:

What is the balance of vascular benefits and diabetes hazard of statin use?


In the randomized, double-blind JUPITER trial, 17,603 men and women without previous cardiovascular disease or diabetes were randomly assigned to rosuvastatin 20 mg or placebo and followed up for up to 5 years for the primary endpoint (myocardial infarction, stroke, admission to hospital for unstable angina, arterial revascularization, or cardiovascular death) and the protocol-prespecified secondary endpoints of venous thromboembolism, all-cause mortality, and incident physician-reported diabetes. In this analysis, participants were stratified on the basis of having none or at least one of four major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body mass index 30 kg/m2 or higher, or glycated hemoglobin A1c >6%.


Trial participants with one or more major diabetes risk factor (n =11,508) were at higher risk of developing diabetes than were those without a major risk factor (n = 6,095). In individuals with one or more risk factors, statin allocation was associated with a 39% reduction in the primary endpoint (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.47–0.79; p = 0.0001), a 36% reduction in venous thromboembolism (HR, 0.64; 95% CI, 0.39–1.06; p = 0.08), a 17% reduction in total mortality (HR, 0.83; 95% CI, 0.64–1.07; p = 0.15), and a 28% increase in diabetes (HR, 1.28; 95% CI, 1.07–1.54; p = 0.01). Thus, for those with diabetes risk factors, a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factors, statin allocation was associated with a 52% reduction in the primary endpoint (HR, 0.48; 95% CI, 0.33–0.68; p = 0.0001), a 53% reduction in venous thromboembolism (HR, 0.47; 95% CI, 0.21–1.03; p = 0.05), a 22% reduction in total mortality (HR, 0.78; 95% CI, 0.59–1.03; p = 0.08), and no increase in diabetes (HR, 0.99; 95% CI, 0.45–2.21; p = 0.99). For such individuals, a total of 86 vascular events or deaths were avoided with no new cases of diabetes diagnosed. In analysis limited to the 486 participants who developed diabetes during follow-up (270 on rosuvastatin vs. 216 on placebo; HR, 1.25; 95% CI, 1.05–1.49; p = 0.01), the point estimate of cardiovascular risk reduction associated with statin therapy (HR, 0.63; 95% CI, 0.25–1.60) was consistent with that for the trial as a whole (HR, 0.56; 95% CI, 0.46–0.69). By comparison with placebo, statins accelerated the average time to diagnosis of diabetes by 5.4 weeks (84.3 [standard deviation, 47.8] weeks on rosuvastatin vs. 89.7 [50.4] weeks on placebo).


The authors concluded that the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard.


This analysis suggests that the risk of development of diabetes on statin therapy seems limited to people with baseline evidence of impaired fasting glucose, metabolic syndrome, severe obesity, or raised glycated hemoglobin A1c (i.e., a group of patients already at high risk of developing diabetes. Furthermore, the cardiovascular and mortality benefits of statin therapy exceeded the diabetes hazard in the trial population as a whole, as well as in participants at increased risk of developing diabetes. These data should provide reassurance for patients and physicians about the use of lipid lowering as an adjunct to diet, exercise, and smoking cessation in the primary prevention of myocardial infarction, stroke, and cardiovascular death.

Keywords: Fluorobenzenes, Myocardial Infarction, Stroke, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Venous Thromboembolism, Pyrimidines, Glucose, Metabolic Syndrome, Body Mass Index, Obesity, Morbid, Cardiology, Cardiovascular Diseases, Diabetes Mellitus, Fasting, Smoking Cessation, Sulfonamides

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