These findings are published in the August 11, 2012 issue of Lancet.
“Our data indicate that the risk of developing diabetes while on statin therapy was limited almost entirely to people who had at least one major risk factor for diabetes prior to initiating statin therapy,” said Paul M Ridker, MD, director for the Center for Cardiovascular Disease Prevention at BWH and lead author of the new study. “Yet even in this high risk group, the benefits of treatment in terms of life-threatening cardiac events avoided greatly outweighed the diabetes hazard.”
“What matters for optimal patient care is the balance of risk and benefit,” Ridker said. “The new data will inform physician-patient discussion and ease concern about risks associated with statin therapy when these drugs are appropriately prescribed for cardiovascular risk reduction in addition to dietary discretion, increased exercise, and smoking cessation.”
The researchers evaluated data from the contemporary JUPITER trial, a multinational, randomized, double-blind study in which 17603 men and women with no previous cardiovascular disease or diabetes received either a statin (rosuvastatin 20 mg daily) or a placebo and were followed for up to five years. Researchers tracked the number of people who developed diabetes while on treatment as well as the number of people who experienced a heart attack, stroke, invasive cardiac revascularization procedure, deep vein thrombosis, pulmonary embolism, or death from any cause. For the analysis, researchers categorized study participants into those at low or high risk for developing diabetes, the latter defined as having at least one major diabetes risk factor such as impaired fasting glucose, metabolic syndrome, severe obesity, or elevated HbA1c (a marker for abnormal glucose metabolism).
Dr. Ridker and his colleagues report that in patients without a risk factor for diabetes, rosuvastatin was associated with a 52 percent reduction in major cardiovascular events (such as heart attack, stroke, coronary revascularizations, or cardiovascular death) and no increase in diabetes. In these individuals, 86 vascular events or deaths were avoided with zero cases of diabetes diagnosed.
In patients with a major risk factor for diabetes, rosuvastatin was associated with a 39 percent reduction in heart attack, stroke, coronary revascularizations, and cardiovascular death; in these participants at high risk for diabetes, a total of 134 vascular events or deaths were avoided for every 54 new cases of diabetes diagnosed.
Overall, among those randomly allocated to statin treatment instead of placebo, the time to diagnosis of diabetes increased by 5.4 weeks. In current practice guidelines, most diabetic patients are already considered to be candidates for statin therapy.
“Whether there is a microvascular risk associated with this extra 40 days of treatment remains unknown” Ridker said. “We know with certainty, however, that large vessel events like heart attack and stroke are clearly reduced with early and more aggressive therapy.”
The researchers note that a limitation of their study is that all patients involved had an elevated high-sensitivity C-reactive protein (hsCRP) level, which is an inflammatory risk factor for the development of both type 2 diabetes and cardiovascular events.
Dr. Ridker and his colleagues encourage additional research that focuses on the unknown biological mechanisms that underlay the association between statin use and diabetes risk. Dr. Ridker also emphasized that exercise and dietary discretion remain the most important issues for preventing both diabetes and heart disease, and that no drug treatment is a substitute for these critical lifestyle issues.
Led by Dr. Ridker, JUPITER was a randomized, double-blind, placebo-controlled trial conducted by investigators in 26 countries and overseen by a fully independent Data and Safety Monitoring Board. The academic study statistician was Professor Robert Glynn, also of BWH and Harvard Medical School. The trial was funded by AstraZeneca, US who played no role in analysis or interpretation of the study data nor in manuscript preparation. Dr. Ridker is listed as a co-inventor on patents held by BWH that relate to the use of inflammatory biomarkers in cardiovascular disease that have been licensed to AstraZeneca and Siemens Healthcare Diagnostics in the therapeutic and diagnostics field respectively.
Brigham and Women’s Hospital