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Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic
Jaapjan D Snoep1, Marcel M C Hovens, Jeroen C J Eikenboom
1Department of General Internal Medicine and Endocrinology, Vascular Medicine Unit, Leiden University Medical Center, Leiden, The Netherlands. j.d.snoep@lumc.nl
Insights
Approximately 21% of patients undergoing percutaneous coronary intervention (PCI) show clopidogrel nonresponsiveness, increasing their risk of adverse cardiovascular events. A higher 600-mg loading dose may mitigate these risks.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Research
Background:
- Patients undergoing percutaneous coronary intervention (PCI) with stenting face risks of recurrent coronary events despite clopidogrel therapy.
- Clopidogrel nonresponsiveness, defined as reduced platelet inhibition ex vivo, may explain these recurrent events.
- The prevalence and clinical impact of clopidogrel nonresponsiveness in PCI patients remain unclear.
Purpose of the Study:
- To systematically review the prevalence of laboratory clopidogrel nonresponsiveness in patients undergoing PCI.
- To assess the clinical consequences and associated cardiovascular risks of clopidogrel nonresponsiveness.
Main Methods:
- Systematic review of electronic databases using predefined search strategies.
- Inclusion criteria: PCI patients on clopidogrel, clear method for clopidogrel effect assessment, reporting of nonresponsiveness prevalence or event incidence.
- Prevalence analyzed with linear mixed models; clinical consequences pooled using random-effects models.
Main Results:
- 25 studies including 3688 patients were identified.
- Mean prevalence of clopidogrel nonresponsiveness was 21% (95% CI, 17%-25%).
- Pooled odds ratio for cardiovascular outcome in nonresponsive patients was 8.0 (95% CI, 3.4-19.0).
Conclusions:
- Laboratory clopidogrel nonresponsiveness affects approximately 1 in 5 PCI patients.
- Patients identified as nonresponsive in laboratory settings face significantly higher risks of adverse cardiovascular outcomes.
- A 600-mg clopidogrel loading dose may reduce these risks, warranting confirmation in prospective studies.
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.
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