Poor response to clopidogrel: current and future options for its management

Abstract

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes and/or undergoing percutaneous coronary interventions (PCI). Clopidogrel, a thienopyridine antiplatelet agent, has been used to prevent vascular complication in atherothrombotic patients, to prevent stent thrombosis in patients undergoing PCI, and in long term prevention of cardiovascular and cerebrovascular events. More than 40 million patients in the world receive clopidogrel but unfortunately about 20% of these are either non or poor responders. Several methods have been used to assess clopidogrel-induced antiplatelet effects. However, none of these tests have been fully standardized or fully agreed upon to measure clopidogrel responsiveness. Nevertheless, many studies using different techniques, platelet agonists and definitions, showed that patients with a poor response to clopidogrel have an increased risk of death, reinfarction and stent thrombosis. The mechanisms leading to poor responsiveness are not fully clarified and are likely multifactorial: genetic factors, accelerated platelet turnover, up-regulation of the P2Y(12) pathways, high baseline platelet reactivity, poor compliance, under-dosing and drug-drug interactions. The management of these patients is very difficult, but some evidence showed that a strategy of higher maintenance dose or switch to different thienopyridine (e.g. ticlopidine or prasugrel) or use of glycoprotein IIb/IIIa inhibitors during PCI may be helpful to overcome poor responsiveness and improve the long-term clinical outcome. This paper reviews the impact of clopidogrel poor responsiveness on clinical outcomes, the mechanisms leading to poor effect and the different assays to assess it. Finally, current and future options for its management is discussed.

Validation of a New ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay to Assess Platelet Reactivity Index in a Chinese Population

“…1 In order to assess the efficacy of antiplatelet therapy and guide the application of antiplatelet drugs, a variety of platelet function tests have been developed and are widely used in clinical practice. 2,3 Vasodilator-stimulated phosphoprotein (VASP) measurement is the most specific approach to evaluate the extent to which P2Y12 receptors are functionally blocked by a P2Y12 antagonist. 4 Vasodilator-stimulated phosphoprotein is independent of all other factors that interfere with platelet reactivity (PR), particularly glycoprotein GPIIb/IIIa inhibitors that block the final pathway of platelet aggregation.…”

Prediction of high risk of non-adherence to antiplatelet treatment

“…DISCUSSION Antiplatelet therapy is the cornerstone of treatment for patients with ACS and/or those undergoing PCI. The pharmacodynamic response to clopidogrel shows substantial inter-patient variability, and patients with coronary disease and lesser platelet inhibition in response to clopidogrel appear to be at increased risk of cardiovascular events [3,11]. Genetic factors, accelerated platelet turnover, up-regulation of the P2Y12 pathways, high baseline platelet reactivity, poor adherence to medication, under-dosing, and drug-drug interactions play important roles in the antiplatelet effect of clopidogrel [12,21,22].…”

“…Premature discontinuation of clopidogrel, shown to be associated with an increased risk of myocardial infarction (MI) or death, and greater health care expenditure [3][4][5], remains one of the concerns regarding this therapy. Patients identified to have a high risk of non-adherence to clopidogrel may benefit from additional educational interventions aimed at improvement of adherence to clopidogrel instead of instan-taneous switching to newer P2Y12 inhibitors.…”

Antiplatelet Therapy Control: Credibility Gap or Search for New Decisions?

“…Недавние исследования продемонстрировали, что не-достаточный уровень подавления тромбоцитов при лечении аспирином и клопидогрелом, определяемый вы-сокой реактивностью тромбоцитов, также является фак-тором риска возникновения тромбоза стента [12,13]. Вы-сокая реактивность тромбоцитов, несмотря на прием кло-пидогрела, обнаружена у 30% популяции западноев-ропейских стран и США и зависит от различных клини-ческих, фармакологических и генетических факторов [4,[13][14].…”

“…Вы-сокая реактивность тромбоцитов, несмотря на прием кло-пидогрела, обнаружена у 30% популяции западноев-ропейских стран и США и зависит от различных клини-ческих, фармакологических и генетических факторов [4,[13][14]. Пациентам, перенесшим тромбоз стента, а так-же пациентам с высоким риском атеротромботических событий, включая повторный тромбоз стента, обыкно-венно назначается двойная антитромбоцитарная тера-пия аспирином и клопидогрелом.…”