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High-sensitivity C-reactive protein and clopidogrel treatment in patients at high risk of cardiovascular events: a substudy from the CHARISMA trial
  1. Michael Weber1,
  2. Deepak L Bhatt2,
  3. Danielle M Brennan3,
  4. Graeme J Hankey4,
  5. Steven R Steinhubl5,
  6. S Claiborne Johnston6,
  7. Gilles Montalescot7,
  8. Koon-Hou Mak8,
  9. Keith AA Fox9,
  10. Donald J Easton10,
  11. Eric J Topol11,
  12. Christian W Hamm1,
  13. for the CHARISMA Investigators
  1. 1Kerckhoff Heart Center, Department of Cardiology, Bad Nauheim, Germany
  2. 2Brigham and Women's Hospital, Boston, Massachusetts, USA
  3. 3Cleveland Clinic, Cleveland, Ohio, USA
  4. 4Department of Neurology, University of Western Australia, Perth, Australia
  5. 5The Medicines Company, Zurich, Switzerland
  6. 6Department of Neurology, University of California, San Francisco, California, USA
  7. 7Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France
  8. 8Mak Heart Clinic and Yong Loo Lin School of Medicine, Singapore, China
  9. 9University and Royal Infirmary, Edinburgh, UK
  10. 10Department of Neurology, Rhode Island Hospital and Brown University, Providence, Rhode Island, USA
  11. 11The Scripps Research Institute and Scripps Clinic, La Jolla, California, USA
  1. Correspondence to Dr Michael Weber, Kreisklinik Gross-Umstadt, Department of Cardiology, Krankenhaus Strasse 11, 64823 Gross-Umstadt, Germany; m.weber{at}kreiskliniken-dadi.de

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.

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Footnotes

  • Funding Funding for the CHARISMA trial was provided by Sanofi-Aventis and Bristol-Myers Squibb.

  • Competing interests DLB has received research grants (directly to the institution) from Bristol Myers Squibb, Sanofi Aventis; honoraria (currently donated to non-profits) from Astra Zeneca, Bristol Myers Squibb, Sanofi Aventis; speaker's bureau (not current, over 2 years ago) for Bristol Myers Squibb, Sanofi Aventis; consultant/advisory board (currently donated to non-profits) for Astra Zeneca, Bristol Myers Squibb, Sanofi Aventis; expert testimony regarding clopidogrel (the compensation was donated to a non-profit organisation). GJH has received consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, Bayer and Boehringer Ingelheim and lecture fees from Sanofi-Aventis, Bristol-Myers Squibb, Bayer and Boehringer Ingelheim. SRS has received consulting fees from Sanofi-Aventis, AstraZeneca, Eli Lilly and the Medicines Company. GM has received consulting and lecture fees from Sanofi-Aventis and Bristol-Myers Squibb. KAAF has received consulting fees from Sanofi-Aventis, lecture fees from Sanofi-Aventis and Bristol-Myers Squibb and grant support from Sanofi-Aventis. JDE has received consulting fees from Sanofi-Aventis and Bristol-Myers Squibb. EJT has served as a consultant to and has received lecture fees from Sanofi-Aventis and Bristol-Myers Squibb before 2005. CWH has received consulting and lecture fees from Sanofi-Aventis. MW, DMB, SCJ and K-HM declare no conflicts of interest.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the institutional ethics committee of each participating institution as well as the appropriate national ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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