SAN DIEGO — Patients with normal lipid levels but elevated C-reactive protein showed a 48% reduction in the risk of stroke when taking rosuvastatin, according to a study presented at the International Stroke Conference.
These results came from a planned additional analysis of JUPITER (Justification for Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin). Investigators presented the main results of this trial, demonstrating a reduction in overall cardiovascular mortality, at the American Heart Association meeting last fall (INTERNAL MEDICINE NEWS, Dec. 1, 2008, p. 1). The AHA also sponsored the stroke conference.
The JUPITER investigators randomized 17,802 patients to receive either 20 mg/day rosuvastatin or placebo, and they followed the patients for up to 4.5 years. During that time, 33 patients in the rosuvastatin group and 64 patients in the placebo group experienced a stroke, corresponding to a statistically significant reduction of 48% in relative risk.
The Kaplan-Meier survival analysis reported based on the additional analysis revealed that stroke risk in the placebo and rosuvastatin groups began diverging within the first year of the trial. By 4.5 years, about 2% of in the placebo group and about 1% of the rosuvastatin patients had a stroke, for a 1% absolute difference in those patients who were followed for that long.
This difference in absolute risk implies that about 100 patients would have to be treated with rosuvastatin in order to prevent one stroke.
“This wouldn't be very large if the focus was only on preventing stroke,” Robert J. Glynn, Ph.D., Sc.D., said at a press briefing.
“But look at the composite primary outcome. The really striking result here is that the benefit for stroke is almost spot on the benefit for myocardial infarction. And the number needed to treat overall in the population is 25 to prevent a primary vascular event. So I don't think you can view stroke in isolation when making a treatment decision,” said Dr. Glynn, who is a biostatistician at the Harvard School of Public Health, Boston, and one of the coauthors of the study.
Subgroup analyses showed significant reductions in the relative risk of stroke for men but not for women, for patients with a BMI of 29.9 kg/m
The investigators also found significant risk reductions among patients whose C-reactive protein levels were 5 mg/L or above, for patients with LDL cholesterol above 100 mg/dL, for those with low HDL cholesterol, and for those with triglyceride levels below 150 mg/dL.
In commenting on the results, Dr. Cheryl Bushnell of Wake Forest University, Winston-Salem, N.C., noted that “C-reactive protein is elevated generally in people who are obese and do not exercise. The question is, are we going to tell these people to do anything differently based on elevated C-reactive protein? If so, we would be treating a lot of extra people with this therapy that we may not have otherwise treated,” he observed.
“There's a really important discussion that has to happen in terms of the risks and benefits of treatment, and the cost of giving C-reactive protein tests as well,” said Dr. Bushnell, who was not affiliated with the study.
Dr. Glynn received grant support for this investigation from AstraZeneca, which manufactures rosuvastatin under the brand name Crestor.