Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis

Snoep, Jaapjan D.; Hovens, Marcel M.C.; Eikenboom, Jeroen C.J.; van der Bom, Johanna G.; Jukema, J. Wouter; Huisman, Menno V.

doi:10.1016/j.ahj.2007.04.014

« Previous Next »American Heart Journal
Volume 154, Issue 2 , Pages 221-231, August 2007

Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: A systematic review and meta-analysis

Jaapjan D. Snoep, MSc
- Department of General Internal Medicine and Endocrinology, Vascular Medicine Unit, Leiden University Medical Center, Leiden, The Netherlands
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
- Reprint requests: Jaapjan D. Snoep, MSc, Department of General Internal Medicine, Leiden University Medical Center, Vascular Medicine Unit, C-04-70, PO Box 9600, 2300 RC Leiden, The Netherlands.
Marcel M.C. Hovens, MD
- Department of General Internal Medicine and Endocrinology, Vascular Medicine Unit, Leiden University Medical Center, Leiden, The Netherlands
Jeroen C.J. Eikenboom, MD, PhD
- Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
Johanna G. van der Bom, MD, PhD
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
J. Wouter Jukema, MD, PhD
- Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Menno V. Huisman, MD, PhD
- Department of General Internal Medicine and Endocrinology, Vascular Medicine Unit, Leiden University Medical Center, Leiden, The Netherlands

Received 28 November 2006; accepted 4 April 2007. published online 23 May 2007.

Background

Despite clopidogrel therapy, patients undergoing percutaneous coronary intervention (PCI) with stenting are at risk of recurrent coronary events. This could be partly explained by a reduced efficacy of clopidogrel to inhibit platelet aggregation, an ex vivo defined phenomenon called clopidogrel nonresponsiveness or resistance. However, both prevalence and associated cardiovascular risks remain unclear. We systematically reviewed evidence on prevalence and clinical consequences of laboratory clopidogrel nonresponsiveness in patients undergoing PCI.

Methods

Using predefined strategies, we searched electronic databases. To be included, articles should report on PCI patients treated with clopidogrel, contain a clear description of the method used to establish the effects of clopidogrel, and report the prevalence of clopidogrel nonresponsiveness or incidence of cardiovascular events. We analyzed prevalences with a linear mixed model that accounts for study covariates and we pooled odds ratios of clinical consequences with a random-effects model.

Results

We identified 25 eligible studies that included a total of 3688 patients. Mean prevalence of clopidogrel nonresponsiveness was 21% (95% CI, 17%-25%) and was inversely correlated with time between clopidogrel loading and determination of nonresponsiveness and used loading dose. The pooled odds ratio of cardiovascular outcome was 8.0 (95% CI, 3.4-19.0).

Conclusions

Laboratory clopidogrel nonresponsiveness can be found in approximately 1 in 5 patients undergoing PCI. Patients ex vivo labeled nonresponsive are likely to be also “clinically nonresponsive,” as they exhibit increased risks of worsened cardiovascular outcomes. Our results indicate that use of a 600-mg clopidogrel loading dose will reduce these risks, which needs to be confirmed in large prospective studies.