SAN DIEGO—Apparently healthy people without hyperlipidemia but with elevated levels of high-sensitivity C-reactive protein (hsCRP) had their stroke risk reduced by about half after treatment with rosuvastatin, according to findings from a study presented by Robert J. Glynn, PhD, ScD, and colleagues at the 2009 International Stroke Conference.
JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) was a primary prevention study enrolling 17,802 adults (men 50 and older and women 60 and older) without cardiovascular disease or diabetes at baseline. To be eligible for inclusion, participants had to have an LDL cholesterol level of less than 130 mg/dL and an hsCRP level of 2 mg/dL or greater. Patients were randomized to treatment with either rosuvastatin (20 mg/day) or placebo.
Stroke Risk Cut By Half With Statin Therapy
After a mean of 1.9 years, treatment with rosuvastatin was associated with a 44% reduction in the primary end point (a composite of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes), compared with placebo treatment.
The rosuvastatin group experienced a 48% reduction in the relative risk of any stroke, compared with the placebo group. With regard to stroke subtype, rosuvastatin was associated with a 51% reduction in the risk of ischemic stroke and a nonsignificant 33% reduction in the risk of hemorrhagic stroke, although only 15 hemorrhagic strokes occurred in the study overall.
The reduction in the occurrence of stroke with rosuvastatin treatment occurred soon after randomization, and the difference in stroke rates between the rosuvastatin and placebo groups expanded over time, said Dr. Glynn, Associate Professor of Medicine at Harvard Medical School and Associate Professor of Biostatistics at Harvard School of Public Health in Boston.
The benefits of treatment were consistent across all subgroups examined, including high-risk groups such as individuals older than 65, those with hypertension, and those with a Framingham risk score greater than 10.
This benefit of rosuvastatin for stroke prevention was greater than that achieved with statin therapy in other randomized clinical trials, said Dr. Glynn. In previous trials, the risk of stroke was reduced by 19% to 48% with statin therapy, but patients enrolled in these trials had established vascular disease or diabetes, placing them at higher risk of subsequent vascular events.
Benefits Beyond Stroke Prevention
Critics point out that although the magnitude of the relative reduction in stroke risk was large, the absolute reduction in risk amounted to about 1%. Subjects enrolled in the trial were at low risk at baseline, and this low risk accounted for the small reduction in absolute risk. In addition, finding eligible participants for the JUPITER trial was difficult, as almost 90,000 patients had to be screened to find those who met the enrollment criteria. However, more than half of the ineligible patients had cholesterol levels that were too high, and the investigators hesitated to assign these patients to a possible placebo treatment.
According to Dr. Glynn, 100 persons who fit the inclusion criteria for the JUPITER trial would have to be treated for four to five years to prevent one stroke. The cost-effectiveness of such an approach has thus been questioned, but he pointed out that the benefits of treatment with rosuvastatin in this population extended beyond stroke prevention. “The [number needed to treat] for the overall population was 25 to prevent a primary vascular event, so I don’t think you can use stroke in isolation when making a treatment decision,” he said.
Dr. Glynn estimated that about 250,000 primary cardiovascular end points could be prevented over a period of five years if all people in the US who met the trial’s eligibility criteria took rosuvastatin.
—Wayne Kuznar