For certain subsets of patients—those at an “intermediate risk” for cardiovascular (CV) disease and who have low LDL cholesterol levels and elevated high-sensitivity C-reactive proteins (hsCRP)—the use of rosuvastatin (Crestor, AstraZeneca) significantly decreases CV risk, according to the results of a substudy of the JUPITER trial published in the September edition of Circulation: Cardiovascular Quality Outcomes.
“In 2009, the Canadian Cardiovascular Society (CCS) issued new primary prevention guidelines recommending measurement of hsCRP along with LDL cholesterol and HDL cholesterol among otherwise healthy men and women at ‘intermediate risk,’” the authors wrote. “[H]sCRP has been found useful in reclassifying risk for intermediate risk men and women in several cohorts.”
Because of the guidelines put forth by CCS and to bulk up on previous data, Paul M. Ridker, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues stratified data to better evaluate the vascular risk in the aforementioned patient population by using data from the JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial.
The JUPITER trial compared the effects of rosuvastatin to placebo in 17,802 patients with LDL cholesterol rates of less than 130 mg/dL and hsCRP that was greater or equal to 2 mg/L. Results showed that use of 20 mg dose of rosuvastatin led to a 44 percent decrease in an occurrence of a first vascular event.
For the current substudy, Ridker and colleagues classified patients according to 10-year global risk estimates using the Framingham risk score and the Reynolds risk score, which estimates 10-year CV risk using hsCRP, among other factors.
The researchers identified 6,091 patients—2,525 women and 3,566 men—that had estimated 10-year Framingham risks of 5 to 10 percent. Additionally 7,340 patients—1,404 women and 5,936 men—had Framingham risks between 11 and 20 percent.
“Because the JUPITER population was selected on the basis of having LDL cholesterol of less than 130 mg/dL, none would have qualified for statin therapy according to guidelines in effect at study entry in 2003,” the authors wrote.
Ridker and colleagues reported that patients with higher 10-year global risk estimates were older, more likely had hypertension and metabolic syndrome and less likely had elevated HDL cholesterol.
The researchers said that patients within the JUPITER trial had median 10-year risks of almost 10 percent, while use of the Framingham risk score or Reynolds risk score reclassified patients into lower and higher 10-year risk categories of less than 5 percent and greater than 20 percent.
With Framingham risk adjustment, patients saw similar levels of risk reductions with rosuvastatin compared to the results of the JUPITER trial.
For patients at an intermediate risk, hazard ratios compared with placebo for the trial endpoints were 0.55 for patients with a 5 to 10 percent risk and 0.51 for those with an 11 to 20 percent risk.
These hazard ratios when the Reynolds risk score was used were reported to be 0.45 and 0.65, respectively.
The authors also evaluated absolute risk reductions when assessed by either the Framingham risk score or the Reynolds risk score. Results showed that absolute risk reductions increased with an increased level of global risk from either of the assessments. This suggested that “this group—currently outside treatment guidelines and with mean entry LDL cholesterol of only 104 mg/dL—might be well considered candidates for statin therapy,” the authors wrote.
“Within the JUPITER trial, we found no evidence that the safety profile of rosuvastatin differed significantly according to baseline level of global risk estimated by either the Framingham risk score or the Reynolds risk score,” the authors wrote.
Additionally, the researchers said that the current research backs the 2009 CCS guidelines that statin therapy for men over 50 and woman over 60 with Framingham risk scores of over 10 percent and hsCRP levels of 2 mg/L or greater is acceptable and reduces risk.
“As in any analysis of a completed trial, caution must be used when interpreting subgroups,” the authors cautioned.
“In sum, in primary prevention patients with low LDL cholesterol and elevated hsCRP who are at 5 percent to 10 percent or 10 percent to 20 percent 10-year risk using either Framingham or Reynolds risk scores, rosuvastatin 20 mg significantly reduces the risk of future