The Impact of High On-Treatment Platelet Reactivity on Cardiovascular Outcomes Following Percutaneous Coronary Intervention: A Review of the Evidence on Clopidogrel Response

Abstract

Introduction: The prevention of thrombotic complications after percutaneous coronary intervention (PCI) with stenting relies on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Despite this standard of care, a subset of patients experiences recurrent ischemic events, suggesting a significant variability in individual response to therapy.

Literature Review: A review of the pivotal literature establishes the clinical importance of high on-treatment platelet reactivity (HTPR), a phenomenon often termed "clopidogrel resistance." A large body of prospective observational studies consistently and powerfully demonstrated that patients exhibiting HTPR, as measured by various platelet function assays, have a significantly higher risk of major adverse cardiovascular events, most notably the catastrophic complication of stent thrombosis. The primary mechanism underlying this variability was elucidated through landmark pharmacogenomic research. These studies identified that common loss-of-function genetic variants in the hepatic enzyme CYP2C19, which is essential for metabolizing clopidogrel into its active form, are a major determinant of HTPR and are strongly associated with an increased risk of adverse clinical outcomes.

Conclusion: The evidence reviewed confirms that HTPR is a critical, independent predictor of adverse ischemic events following PCI. This research established a clear phenotypic and genotypic basis for the variable efficacy of clopidogrel and created the foundational rationale for a personalized approach to antiplatelet therapy to overcome treatment resistance.