Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial

Background As statin therapy increases risks of diabetes, the balance of benefit and risk in primary prevention for these agents has become controversial. We undertook an analysis of participants from the JUPITER trial to address the balance of vascular benefits and diabetes hazard of statin use. Methods In the randomized, double-blind JUPITER trial, 17,603 men and women without prior cardiovascular disease or diabetes were randomly allocated to rosuvastatin 20 mg or placebo and followed for up to 5 years for the trial primary endpoint (myocardial infarction, stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death) and the protocol pre-specified secondary endpoints of venous thromboembolism (VTE), all-cause mortality, and incident diabetes. To address balance of vascular benefits and diabetes hazard, participants were stratified on the basis of having none or at least one of the following major risk factors for developing diabetes: metabolic syndrome, impaired fasting glucose, body mass index >30 kg/m2, or HbA1c > 6 percent. Findings Trial participants with one or more major diabetes risk factor (N=11,508) were at higher risk of developing diabetes; for such individuals, statin allocation was associated with a 39 percent reduction in the primary endpoint (P=0.0001), a 36 percent reduction in VTE (P=0.08), a 17 percent reduction in total mortality (P=0.15) and a 28 percent increase in diabetes (P=0.01). Thus, for those with diabetes risk factors, 93 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed. For trial participants with no major diabetes risk factor (N=6,095), statin allocation was associated with a 52 percent reduction in the primary endpoint (P=0.0001), a 53 percent reduction in VTE (P=0.05), a 22 percent reduction in total mortality (P=0.08) and no increase in diabetes (HR 0.99, 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 group, P=0.01), the point estimate of cardiovascular risk reduction associated with statin therapy (hazard ratio 0.63) was consistent with that observed for the trial as a whole (hazard ratio 0.56). As compared to placebo, statin allocation accelerated the average time to diagnosis of diabetes by 5.4 weeks. Interpretation In the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including among those at higher risk for developing diabetes