Monitoring Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Dual antiplatelet therapy with aspirin and thienopyridines is the cornerstone in the treatment of patients with acute coronary syndrome (ACS) and in those undergoing PCI with stent-implantation.However, the magnitude of on-treatment platelet reactivity is not uniform among individuals, due to a multifactorial origin including clinical, pharmacologic and genetic factors. Clopidogrel is a prodrug that requires conversion by hepatic P450 isoenzymes to its active metabolite. Most of the clopidogrel (85%) is hydrolyzed by carboxylase to an inactive carboxylic acid metabolite, whereas the remaining 15% is transformed rapidly into its active metabolite that is able to exert its antiplatelet response by irreversibly inhibiting the binding of adenosinediphosphate (ADP) to the P2Y12 receptor. Recently, paraoxonase-1 (PON1) was identified as the crucial enzyme in clopidogrel bioactivation. Consistent findings across multiple investigations support the association between a lower degree of platelet inhibition, i.e. a high on-treatment platelet reactivity (HPR), and an increased risk for the occurrence of thrombo-ischemic events (Table 1).9-14,14,15,15-27 Multiple factors have been associated with high on-treatment platelet reactivity, among which genetic polymorphisms of cytochrome P450 and of the P2Y12 receptor as well as and drug-drug interactions. Consequently, the monitoring of the magnitude of platelet reactivity has gained widespread attention

Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention

Background: The carriage of CYP2C19*2 and the use of proton-pump inhibitors (PPIs) and calcium-channel blockers (CCBs) has been associated with the diminished efficacy of clopidogrel. However, previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response. Objectives: The aim of the present study was to investigate the impact of the combined presence of three risk factors for clopidogrel poor response, that is, the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting. Methods: In a prospective, follow-up study, on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. The clinical study endpoint was the composite of all-cause mortality, myocardial infarction, stent thrombosis and stroke at 1year after stenting. Results: Patients with either one or more than one risk factor exhibited increased platelet reactivity (mean relative increase one risk factor: 11% and >1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up (8.8% of the study population). Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint. However, patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a statistically significant increased risk of the composite endpoint [hazard ratio(HR)adj2.2 95% CI, 1.0-5.3, P=0.044 and HRadj3.3 95% CI, 1.1-9.8, P=0.032, respectively]. Conclusions: The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1year after elective coronary stenting. © 2011 International Society on Thrombosis and Haemostasis

Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention: subgroup analysis from the WOEST trial

Item does not contain fulltextAIMS: To investigate the optimal periprocedural antithrombotic strategy in patients on long-term oral anticoagulation (OAC) who require percutaneous coronary intervention with stenting. METHODS AND RESULTS: The WOEST study was a randomised controlled trial which recruited 573 patients on long-term OAC who underwent PCI. The periprocedural treatment strategy was left to the operator's discretion. To assess the safety and feasibility of uninterrupted oral anticoagulation (UAC) and bridging therapy (BT), bleeding complications and MACCE were assessed in patients treated according to UAC (n=241) and BT (n=322) regimen. After 30 days, as well as after one year, there were no significant differences in bleeding complications (HR 1.14, 95% CI: 0.77-1.69, p=0.51, and HR 1.26, 95% CI: 0.94-1.69, p=0.12, respectively) and MACCE. MACCE tended to be less frequent in the UAC group (respectively HR 0.48, 95% CI: 0.15-1.51, p=0.21, and HR 0.72, 95% CI: 0.46-1.14, p=0.16). Additionally, adjustment with a propensity score revealed no significant differences. Periprocedural INR was not associated with bleeding or MACCE. CONCLUSIONS: In the WOEST study, UAC was not associated with an increase of bleeding or MACCE compared to bridging therapy. This is the largest study up to now to support the current guidelines. The WOEST trial is registered with ClinicalTrials.gov, number NCT00769938