Abstract 815: Comparative Atorvastatin Pleiotropic effects (CAP) study
Background: The beneficial effects of statins in reducing coronary events have been attributed to reductions in LDL-C and inflammatory markers. There is no information on the effects of statins on CRP levels in stable CAD patients with normal range lipoprotein profiles and evidence of chronic low grade inflammation. The aim of CAP was to compare the effect of low and high dose atorvastatin on CRP in such a population, and to determine the relationship between changes in LDL-C and CRP.
Methods: CAP was a 26-week, prospective, multicenter, randomized, double-blind, double-dummy study which enrolled 339 subjects with stable CAD, LDL-C > 50 mg/dL but = 150 mg/dL, hsCRP = 1.5 mg/L but < 15 mg/L, and TG = 400 mg/dL. After a 6-week washout period, subjects were randomized to atorvastatin 10 or 80 mg. Blood samples were obtained at baseline and after 5, 13 and 26 weeks of treatment. The primary endpoint was the change from baseline in hsCRP after 26 weeks.
Results: After 5 weeks, LDL-C decreased by 35.9% in the 10 mg group and by 52.7% in the 80 mg group (p<0.001) and remained stable thereafter. Overall, 77% and 92% of subjects reached LDL-C target of < 100 mg/dL in the 10 and 80mg groups, respectively. Mean baseline hs-CRP concentration was 3.13 (95%CI: 2.84, 3.45) and 3.56 (95%CI: 3.22, 3.94) mg/L in the atorvastatin 10 mg and 80 mg groups, respectively. In the 10 mg group, mean hsCRP decreased by 25% at 5 weeks and remained stable thereafter. In the 80 mg group, hsCRP decreased by 36.4% at 5 weeks, but in contrast to the 10 mg group hsCRP continued to decrease progressively over the 26-week study period (−57.1% vs. baseline at 26 weeks; p<0.0001 vs. week 5). The decrease in hsCRP was largely independent of baseline LDL-C (r2=0.017, p=0.01) and change in LDL-C (r2=0.078, p<0.0001), and totally independent of changes in HDL-C (NS) and TG (NS), regardless of dose. Treatment was well tolerated in both study groups.
Conclusion: In patients with stable CAD, low grade inflammation and normal range lipid profiles, the effect of atorvastatin on changes in hsCRP is dose-dependent. High-dose atorvastatin induced a marked and progressive decline in hsCRP independently of changes in LDL-C.