NEW YORK (Reuters Health) – In older patients with normal lipids but high C-reactive protein, primary prevention therapy with rosuvastatin (Crestor) does not lower mortality, but it does reduce major cardiovascular events.
Furthermore, the absolute benefit of rosuvastatin on this endpoint was greater in older vs younger subjects. These findings, reported April 20th in the Annals of Internal Medicine, are from a post-hoc analysis of data from the randomized JUPITER trial.
“The magnitude of cardiovascular event reduction associated with rosuvastatin was impressive in older persons,” independent researchers wrote in an editorial published with the study.
JUPITER, first reported in 2008, included more than 17,000 apparently healthy subjects with LDL cholesterol levels less than 130 mg/dL but with high-sensitivity C-reactive protein levels of 2.0 mg/L or more. Men in the study were at least 50 years old; women were at least 60. Subjects received rosuvastatin, 20 mg/day, or placebo. Although the study was to have gone on for 5 years, the research team stopped it early (at a median follow-up of 2 years) when it became clear that treatment reduced cardiovascular morbidity and mortality. (See Reuters Health story, November 10, 2008.)
The original trial design did not stratify randomization by age. For the exploratory analysis, Dr. Robert J. Glynn, from Brigham and Women’s Hospital, Boston, and colleagues examined outcomes for all participants older than age 70 at baseline, including 2878 who took rosuvastatin and 2817 who took placebo.
The researchers set the age cutoff at 70 “because previous primary prevention trials included few persons in this age group and use of statins for primary prevention in older persons is controversial,” according to their article.
The authors could not show any improvement in all-cause mortality with rosuvastatin in the older subjects. The rate per 100 person-years of follow-up was 1.63 with rosuvastatin and 2.04 with placebo (p = 0.09).
The article also notes that although median achieved levels of lipids and C-reactive protein were similar in the older and younger groups during the study, the older subjects sustained 194 (49%) of the 393 primary end points, that is, any first cardiovascular event (a myocardial infarction, stroke, hospitalization for unstable angina, an arterial revascularization procedure, or death of cardiovascular causes).
But rosuvastatin did lower the incidence of first cardiovascular events for the older individuals. Per 100 person years of follow-up, the incidence was 1.22 with rosuvastatin and 1.99 with placebo (hazard ratio 0.61, p < 0.001).
In contrast, among the 12,107 younger trial participants (ages 50 to 69), the incidence of a first cardiovascular event per 100 person-years was 0.54 with rosuvastatin and 1.06 in with placebo (HR 0.51, p < 0.001). Therefore, the absolute reduction in the incidence of primary endpoints was 48% larger in the older age group: 0.77 vs 0.52 events per 100 person-years.
The researchers estimate that with 4 years of treatment, the number needed to treat to prevent one case of the primary endpoint is 24 among older individuals and 36 among younger subjects. They add that when the primary endpoint is expanded to include any death or venous thromboembolism, the number needed to treat drops to 17 in older subjects and 27 in the younger group.
In their editorial, Dr. Susan J. Zieman and Dr. Pamela Ouyang, both affiliated with Johns Hopkins University in Baltimore, try to narrow down the criteria for identifying older patients who might benefit from primary prevention with statins.
Among these, they say, is a Framingham risk score above 20%. Also, they point out, because 75% of the older subjects were no more than 77 years old, “these data apply best to the young-old persons but leave uncertainty about the old-old.”
Finally, the editorialists said, “although the investigators do not provide specific baseline high-sensitivity C-reactive protein levels in this subanalysis, persons with levels less than 5 mg/L had a statistically significant reduction in the primary outcome, whereas those with levels of 5 mg/L or greater did not.” This means, they add, that high-sensitivity C-reactive protein levels can’t really be used as a risk-stratifying tool in older adults.
What’s needed now, the editorial concludes, are more accurate risk-prediction tools for people over age 80, “a rapidly growing and resource-consuming segment of the population.”
The study was funded by Astra Zeneca.
Ann Intern Med 2010;152:488-496,528-530.