JUPITER Analysis to Assess Diabetes Risk with Statins in Primary Prevention

27 Aug, 12

Cardiovascular Benefits of Statin Therapy for Primary Prevention Outweigh Diabetes Risk An Analysis from JUPITER Trial

Background

In primary prevention in low-risk patients, for whom statin therapy is increasingly used for vascular prevention, there has been some controversy as to whether the absolute benefit of statin treatment outweighs the diabetes risk.

Objective

To perform an analysis of JUPITER trial in order to address the balance of vascular benefits and diabetes hazard of statin use in primary prevention, taking into account the risk factors for diabetes.

Study Design

Randomised, double-blind, placebo-controlled study
Individuals were randomized to receive rosuvastatin 20 mg once-daily or placebo for 5 years

Study Participants

Patients with LDL-C< 130 mg/dL and hs-CRP ≥2 mg/dL (n=17, 603) were stratified into two groups:

Patients with 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 haemoglobin A_1C >6%; n= 11, 508)
Patients without any risk factors (n = 6095)

Study Endpoints

Primary endpoint included occurrence of first cardiovascular event (myocardial infarction, stroke, admission to hospital for unstable angina, arterial revascularization or cardiovascular death)
Secondary endpoints were venous thromboembolism, physician-reported diabetes and all-cause mortality

Results

Patients with one or more major diabetes risk factors had an increased risk of developing diabetes during trial follow-up, with an incidence rate of 1.88 per 100 person-years, compared with 0.18 per 100 person-years in those with no risk factors.
In patients with one or more risk factors, statin therapy was associated with a significant 39%, 36% and 17% reduction in primary endpoint, venous thromboembolism and total mortality, respectively. However, it was associated with a significant 28% increase in diabetes. Thus, a total of 134 vascular events or deaths were avoided for every new 54 new cases of diabetes diagnosed in this group.
In patients with no major risk factors, statin allocation was associated with a significant 52% reduction in primary endpoint, a 53% reduction in venous thromboembolism, a 22% reduction in total mortality and no increase in diabetes risk. Thus, in this group, a total of 86 vascular events or deaths were avoided with no excess new cases of diabetes diagnosed.
Risk of diabetes associated with rosuvastatin allocation did not change substantially as the number of major diabetes risk factors increased.

Conclusion

The risk of developing diabetes with statin therapy is limited to patients already at a high risk for developing diabetes. However, in these high-risk patients, as well as in the entire study cohort, the benefits of statin therapy exceeded the risk of diabetes.
This data should provide a reassurance for physicians about the use of statins for primary prevention.

These findings reaffirm the net value of statins in the primary prevention of cardiovascular disease, but intuitively caution that the diabetogenic effect of these drugs is highest in individuals with risk factors for diabetes, including raised CRP. Conversely, in their absence, the risk of diabetes is negligible.

- Gerald F Watts and Esther M Ooi, University of Western Australia, Perth (In an accompanying editorial)

A major take-home message for the clinician involved in either primary or secondary prevention of cardiovascular disease is that all individuals on a statin who have major risk factors for diabetes, particularly impaired fasting glucose, need to be informed about the risk, monitored regularly for hyperglycaemia and advised to lose weight and take regular exercise to mitigate the emergence of diabetes.

- Gerald F Watts and Esther M Ooi, University of Western Australia, Perth (In an accompanying editorial)

Lancet 2012;380:565-71
Lancet 2012;380:541-543