Statin Prevents Events in Patients With IFG

ORLANDO — Rosuvastatin proved markedly effective for the primary prevention of major cardiovascular events in patients with impaired fasting glucose in a secondary analysis from the JUPITER trial.

This is the first solid proof of a primary prevention benefit for statin therapy in patients with impaired fasting glucose (IFG). Statins are guideline-recommended for nearly all diabetes patients, but until now there has been little supporting evidence of a cardiovascular benefit in otherwise healthy individuals with IFG.

That is, until JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), which included 5,504 participants with baseline IFG, Dr. Aruna Pradhan said at the annual scientific sessions of the American Heart Association.

On the downside, rosuvastatin therapy also was associated with a significantly increased rate of new-onset diabetes compared with placebo. The risk was of similar magnitude in rosuvastatin-treated subjects with baseline IFG and in those with normal fasting glucose. This phenomenon appears to be a statin class effect, as it has also been consistently seen in major placebo-controlled trials involving other statins, said Dr. Pradhan of Brigham and Women's Hospital, Boston.

JUPITER randomized 17,802 men and women with no prior cardiovascular disease or diabetes to 20 mg/day of rosuvastatin (Crestor) or placebo. All participants had a high-sensitivity C-reactive protein level of 2.0 mg/L or more and an LDL cholesterol below 130 mg/dL. The prevalence of metabolic syndrome was 74% among those with baseline IFG and 27% in those with normal fasting glucose.

JUPITER was halted after a median 1.9 years of follow-up, after the data and safety monitoring board determined that rosuvastatin had an “unequivocal benefit” on coronary-related death and disability. At that time, the rosuvastatin-treated subjects with IFG had a 32% reduction in the risk of the primary composite end point, comprised of MI, stroke, hospitalization for unstable angina, coronary revascularization, or cardiovascular death, compared with placebo-treated participants with IFG. This benefit was not significantly different in magnitude from the 49% relative risk reduction seen in rosuvastatin-treated subjects with baseline normal fasting glucose, Dr. Pradhan noted.

There were 182 cases of physician-diagnosed incident diabetes in subjects with IFG on rosuvastatin, compared with 145 arising in those on placebo, a 30% increase in risk. This was statistically similar to the 26% relative risk associated with rosuvastatin in the normal fasting glucose group, although the absolute number of cases of diabetes in subjects with baseline normal fasting glucose was far smaller: 54 cases in rosuvastatin-treated subjects compared with 43 in controls.

Dr. Pradhan noted that this finding of a rosuvastatin-associated increase in new-onset diabetes in JUPITER is consistent with the results of a recent meta-analysis led by investigators at Albert Einstein College of Medicine in New York.

The meta-analysis included nearly 58,000 participants in nine major placebo-controlled randomized statin trials. During a mean follow-up of 3.9 years, more than 2,000 cases of new-onset diabetes occurred. Only the first of the trials—the West of Scotland Coronary Prevention Study (WOSCOPS)—found that statin therapy reduced new-onset diabetes. The next eight studies, including such landmark trials as the Heart Protection Study (HPS) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), as well as JUPITER, collectively showed a significant 13% increase in incident diabetes in statin-treated subjects (Diabetes Care 2009;32:1924-9).

A meeting attendee asked whether diabetes arising in statin-treated patients might behave differently, perhaps with less associated cardiovascular risk. JUPITER is unlikely to provide an answer, Dr. Pradhan replied. Because the trial was halted after a median of 1.9 years, there was not enough time for a large number of cardiovascular events to accrue following the diagnosis of diabetes.