High dose statin reduces cardiac events in patients with high CRP

Clinical question In patients with normal LDL cholesterol but elevated Creactive protein (CRP), is a high-dose statin effective for primary cardiovascular prevention?

Bottom line In this study of patients with normal LDL and elevated CRP, use of a high-dose statin reduced the risk of death over a 2-year period (number needed to treat [NNT] = 180). At a cost of approximately $1,200/y for rosuvastatin, the cost per life saved is about $216,000. This study raises many questions. What is the long term safety of lowering LDL cholesterol to 55 mg/dL in otherwise healthy persons? What is the impact of the apparent increase in diabetes on the long-term benefit of this drug? Can less expensive statin drugs, perhaps at lower doses, provide a similar benefit with less risk? (Level of evidence = 1a)

Synopsis The Air Force/Texas Coronary Atherosclerosis Prevention Study found that statins may be effective in patients with normal cholesterol but elevated levels of CRP, a measure of inflammation. In this study, the authors identified adults with LDL cholesterol less than 130 mg/dL and CRP higher than 2.0 mg/L. Nearly 90,000 men over age 50 years and women over age 60 years were screened for enrollment in the trial, and the vast majority were excluded because of an elevated LDL (37,611), low CRP (25,993), withdrawal of consent (3,948), diabetes (957), hypothyroidism (349), or other reasons. Patients with preexisting heart disease or who had ever taken a statin or hormone replacement therapy were ineligible, as were patients with elevated creatine kinase, creatinine, or hepatic transaminases at baseline. The remaining 19,323 patients took placebos for 4 weeks to assess their compliance, and those taking less than 80% of the study drug were excluded. This of course has the effect of making the study drug look more effective than it is in the real world of clinical practice. The remaining 17,802 patients (62% male, 75% white, mean age 66 years) were randomized to rosuvastatin (Crestor), 20 mg once daily, or matching placebo. At each of the annual follow-up visits, the LDL in the rosuvastatin group was approximately half that of the placebo group (55 vs 110 mg/dL) and the CRP was also significantly lower (~2.0 vs 3.5 mg/L). The study was terminated early after 1.9 years of median follow-up. At that time, all cause mortality was lower in the rosuvastatin group (1.0 vs 1.25 per 100 patient years, P = .02). There was a consistent pattern of fewer cardiovascular events for patients taking rosuvastatin, including fewer MI (0.17 vs 0.37 per 100 patient years, P = .0002) and fewer strokes (0.18 vs 0.34 per 100 patient years, P = .002). Patients taking rosuvastatin were more likely to be diagnosed with diabetes mellitus (270 vs 216 cases, P = .01). There was only one reported case of rhabdomyolysis, which occurred in a patient taking rosuvastatin.