Some previous studies – most noticeably the JUPITER trial – have suggested that the vascular benefits of statin therapy may be greater in the presence of inflammation. C-reactive protein (CRP), a systemic marker of inflammation, has been associated with the risk of ischaemic heart disease, stroke, and vascular mortality, but its ability to act as a biomarker that can be used to guide treatment remains controversial. This study tested the hypothesis that the effects of statin therapy differ according to baseline concentrations of CRP and LDL cholesterol.
Using data from the Heart Protection Study (HPS), the largest randomised trial of statin therapy, the authors studied 20 536 men and women aged 40—80 years who were randomly assigned to simvastatin 40 mg daily versus matching placebo. Patients were categorised into six baseline CRP groups (<1·25, 1·25—1·99, 2·00—2·99, 3·00—4·99, 5·00—7·99, and ≥8·00 mg/L). The primary endpoint used was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation.
Overall, patients taking simvastatin showed a 24% (95% CI 19—28) proportional reduction in the incidence of first major vascular event (2033 [19·8%] vs 2585 [25·2%] ). However, no proportional reduction in the primary endpoint, or its components, was seen in different baseline CRP concentration groups (trend p=0·41, figure). This included patients with a baseline CRP concentration less than 1·25 mg/L, in whom major vascular events were significantly reduced by 29% (p<0·0001). Furthermore, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, p<0·0001).
In this large study of high-risk patients, the vascular benefits of simvastatin were seen regardless of CRP and LDL concentrations at baseline.
- Heart Protection Study Collaborative Group. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study. Lancet. 2011;377:469-476.