Clinical Geriatrics

Rosuvastatin in Patients with Normal Cholesterol Levels and Elevated C-Reactive Protein Levels

New Orleans—Rosuvastatin reduced the relative risk of heart attacks, strokes, the need for revascularization, and all-cause mortality in apparently healthy people with normal cholesterol levels but elevated levels of high sensitivity C-reactive protein (hsCRP), a marker of inflammation. These were the main findings of the large randomized, placebo-controlled, double-blind JUPITER trial reported by Paul M. Ridker, MD, lead author of the trial, Director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, Boston, Massachusetts.

“The relative benefits of rosuvastatin were consistent in all subgroups regardless of age, sex, ethnicity, or other baseline characteristics, including persons with elevated hsCRP and no other major cardiovascular risk factor. A reduction in all-cause mortality was seen within 2 years, which should be reassuring for payers. The data are extremely reassuring for statins as a drug class,” Dr. Ridker stated.

JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin), the 26-country, multinational trial was designed to test the hypothesis that statin therapy would be effective among patients with low low-density lipoprotein (LDL) cholesterol levels (<130 mg/dL) and high hsCRP (>2.0 mg/L). This hypothesis stems from the observation in the AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study) trial that vascular event rates were similarly high in apparently healthy individuals with low LDL cholesterol levels and high CRP levels compared with individuals with overt hyperlipidemia (n=1428).

JUPITER randomized 8901 individuals to treatment with rosuvastatin 20 mg and 8901 to receive placebo. The study population had normal LDL cholesterol levels and elevated hsCRP levels and included men over age 50 and women over age 60 with no history of cardiovascular disease or diabetes. However, study participants could have had other cardiovascular risk factors, such as hypertension, obesity, current smoking, abnormal glucose tolerance, and/or the metabolic syndrome, and/or a family history of premature cardiovascular disease. The primary end point was myocardial infarction (MI), stroke, unstable angina/revascularization, and cardiovascular death.

Rosuvastatin reduced the risk of the primary composite end point of the trial by 44% compared with placebo, a difference that was highly statistically significant (P<.00001). There were 142 major cardiovascular events in the rosuvastatin group versus 251 events in the placebo group. The number of patients needed to treat (NNT) with rosuvastatin for 4 years to prevent one cardiovascular event is 31, and NNT to prevent one cardiovascular event over 5 years is 25. This is an acceptable level compared to other statin trials showing NNT between 45 and 60, he said.

Looking at separate components of end points, rosuvastatin reduced the risk of MI by 64% (P=.0002), the risk of any stroke by 48% (P=.02), and the risk of MI/stroke/confirmed CV death by 47% (P<.00001). Rosuvastatin also reduced the risk of arterial revascularization or hospitalization for unstable angina by 47% (P<.0001). Rosuvastatin reduced the relative risk of the secondary end point of all-cause mortality by 20%, with 198 deaths in the rosuvastatin group versus 247 in the placebo group (P=.02).

Subgroup analysis showed that rosuvastatin was effective in men and women, patients under the age of 65 years and age 65 or over, smokers and nonsmokers, and Caucasians and non-Caucasians. However, the absolute benefit among subgroups was not presented.