High-sensitivity C-reactive protein and clopidogrel treatment in patients at high risk of cardiovascular events: a substudy from the CHARISMA trial

CHARISMA Investigators, Michael Weber, Deepak L. Bhatt, Danielle M. Brennan, Graeme J. Hankey, Steven R. Steinhubl, S. Claiborne Johnston, Gilles Montalescot, Koon-Hou Mak, Keith A. A. Fox, Donald J. Easton, Eric J. Topol, Christian W. Hamm

Research output: Contribution to journalArticlepeer-review

Abstract

Aims This study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are at high risk of atherothrombotic events. The predictive value of hsCRP levels for a treatment benefit of clopidogrel was also explored.

Methods The study included 8021 patients with established atherosclerotic disease or multiple cardiovascular risk factors enrolled in the CHARISMA trial. Patients were randomly assigned either to clopidogrel plus aspirin or placebo plus aspirin. HsCRP was measured at study entry and at study termination (median 28 months). The predefined primary composite endpoint was myocardial infarction, stroke, or death from cardiovascular causes.

Results There was a stepwise increase in the event rate of the combined primary endpoint with increasing quartiles of hsCRP at baseline (4.0%, 6.1%, 7.4% and 8.7% for the highest quartile). In both treatment groups the changes in hsCRP levels over time were identical. In patients with low hsCRP levels (< 3 mg/l) clopidogrel treatment was associated with a lower event rate compared with placebo (4.0% vs 6.0%, log rank p=0.005). In contrast no treatment effect was observed in patients with high hsCRP levels (8.1% vs 8.0%, ns).

Conclusions In this broad population, hsCRP is a powerful predictor of ischaemic events. Compared with placebo, clopidogrel was without effect on inflammatory markers. The reduction in cardiovascular events by antiplatelet treatment with clopidogrel was isolated to patients with low levels of hsCRP.

Original languageEnglish
Pages (from-to)626-631
Number of pages6
JournalHeart
Volume97
Issue number8
DOIs
Publication statusPublished - Apr 2011

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