On March 1, 2012, after experts revealed that statin therapy may increase the risk for diabetes, the FDA added a warning to all statin labels. However, new data from the JUPITER trial suggest that the benefits of statin therapy outweigh the risk for diabetes.
The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was a randomized, double-blind, placebo-controlled study of 17,603 men and women without previous cardiovascular disease (CVD) or diabetes.
Paul M. Ridker, MD, MPH, the Eugene Braunwald professor of medicine at the Harvard Medical School and director of the Center for Cardiovascular Disease Prevention, a translational research unit at the Brigham and Women’s Hospital, and colleagues sought to determine whether rosuvastatin 20 mg (Crestor, AstraZeneca) compared with placebo could decrease the rate of first-ever cardiovascular events in patients with LDL ,130 mg/dL and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. Focus was also emphasized on the effects of rosuvastatin on incident type 2 diabetes.
Patients were randomly assigned to rosuvastatin 20 mg or placebo and were followed for up to 5 years for the primary endpoint (MI, stroke, admission to hospital for unstable angina, arterial revascularisation or cardiovascular death), in addition to the protocol-prespecified secondary endpoints of venous thromboembolism, all-cause mortality and incident physician-reported diabetes.
According to data, patients with one or more major diabetes risk factors (n=11,508) were more likely to be female, have higher baseline BP, HbA1c, glucose, and triglycerides and lower baseline HDL cholesterol compared with those who did not have diabetes risk factors (n=6,095).
“As expected, trial participants with one or more major diabetes risk factor had an increased risk of developing diabetes during trial follow-up,” researchers wrote.
They found that, overall, incident diabetes was more apparent in the rosuvastatin group (270 reports of diabetes vs. 216 in the placebo group; HR=1.25; 95% CI, 1.05-1.49). Additional data showed that for individuals with one or more risk factors, rosuvastatin was linked to a 39% reduction in the primary endpoint (P=.0001), a 36% reduction in venous thromboembolism (P=0.15) and a 28% increase in diabetes (P=.01).
In patients with diabetes risk factors, 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed, researchers wrote. Those without risk factors accounted for 86 vascular events or deaths and no new cases of diabetes were diagnosed, they added.
Among patients assigned to rosuvastatin, CV benefits came with the risk for new-onset diabetes approximately 5 to 6 weeks earlier compared with those in the placebo group, researchers said. It is for this reason that Ridker and colleagues suggest further research.
In an accompanying editorial by Gerald F. Watts, DSc, PhD, DM, FRACP, FRCP, and Esther M. Ooi, PhD, from the Cardiometabolic Research Centre and Clinical Services of Royal Perth Hospital School of Medicine and Pharmacology at the University of Western Australia, said the study was intuitive and based on new evidence. However, Watts and Ooi suggest that independent data from other studies are needed to strengthen a recommendation to the FDA.
“Additionally, the question of whether or not long-term use of statins impairs glycemic control in established diabetes merits investigation, as do the precise macrovascular and microvascular consequences of statin-induced diabetes. Only robust, longer-term cohort data can address these questions,” Watts and Ooi wrote.
Disclosures: The JUPITER trial was funded by AstraZeneca. Dr. Ridker has served as a consultant for various entities, receives additional research grant support from Novartis, and holds patents held by the Brigham and Women’s Hospital which have been licensed to Siemens and AstraZeneca. Several researchers received grant support from AstraZeneca. Dr. Libby was an unpaid consultant involved in clinical trials for various pharmaceutical companies and is a member on several advisory boards. Dr. Watts has received honoraria or lecture fees from AstraZeneca and other pharmaceutical companies. All other researchers report no relevant financial disclosures.
For more information:
- Ridker PM. Lancet. 2012; 380:565-571.
- Watts GF, Ooi EM. Lancet. 2012; 380:541-543.
- ClinicalTrials.gov, NCT00239681.