Genomewide Association Study of Platelet Reactivity and Cardiovascular Response in Patients Treated With Clopidogrel: A Study by the International Clopidogrel Pharmacogenomics Consortium.

Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response.

Derivation, Validation, and Prognostic Utility of a Prediction Rule for Nonresponse to Clopidogrel: The ABCD-GENE Score.

Objectives: The aim of this study was to develop a risk score integrating cytochrome P450 2C19 loss-of-function genotypes with clinical risk factors influencing clopidogrel response that would allow the identification with more precision of subjects at risk for high platelet reactivity (HPR) and adverse clinical outcomes.

Background: Clopidogrel is the most broadly used platelet P2Y inhibitor. However, a considerable number of patients achieve inadequate platelet inhibition, with persistent HPR, an established marker of increased thrombotic risk, underscoring the need for tools to help identify these subjects.

Updated Expert Consensus Statement on Platelet Function and Genetic Testing for Guiding P2Y Receptor Inhibitor Treatment in Percutaneous Coronary Intervention.

Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor is the standard treatment for patients undergoing percutaneous coronary intervention. The availability of different P2Y receptor inhibitors (clopidogrel, prasugrel, ticagrelor) with varying levels of potency has enabled physicians to contemplate individualized treatment regimens, which may include escalation or de-escalation of P2Y-inhibiting therapy. Indeed, individualized and alternative DAPT strategies may be chosen according to the clinical setting (stable coronary artery disease vs.

Perioperative management of antiplatelet treatment in patients undergoing isolated coronary artery bypass grafting in Dutch cardiothoracic centres.

Background: International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG).

Methods: A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014.

How Long Does It Take for Clopidogrel and Ticagrelor to Inhibit Platelets in Patients Undergoing Primary Percutaneous Coronary Intervention? A Detailed Pharmacodynamic Analysis: Time Course of Platelet Reactivity in STEMI (TOPS).

Antiplatelet therapy plays a pivotal role in patients with an ST-segment elevation myocardial infarction (STEMI) to prevent further atherothrombotic events, such as stent thrombosis. Although the risk of stent thrombosis is highest in the first hours after primary percutaneous coronary intervention (pPCI), little is known about when an adequate level of platelet inhibition is achieved following a clopidogrel or ticagrelor loading dose in STEMI patients. Patients presenting with STEMI in whom pPCI was performed and who were loaded with 600 mg clopidogrel or 180 mg ticagrelor were eligible for enrolment in this nonrandomized, open label, single-center study.

Effect of Tailored Antiplatelet Therapy to Reduce Recurrent Stent Thrombosis and Cardiac Death After a First Episode of Stent Thrombosis.

The recurrence rate of coronary stent thrombosis (ST) is high. Patients with ST often demonstrate high on-treatment platelet reactivity (HPR). It is suggested that patients at high risk of atherothrombotic events, that is patients with ST, could benefit from tailored antiplatelet therapy (APT).

Does percutaneous coronary stent implantation increase platelet reactivity?

High platelet reactivity (PR) values on treatment with clopidogrel are associated with an increased rate of thrombotic events after a percutaneous coronary intervention (PCI). However, we do not know the optimal timing of the performance of the PR measurements. Platelets might be activated during a PCI, which means that the timing of PR measurements, before or after PCI, could influence the outcome.

The effect of correcting VerifyNow P2Y12 assay results for hematocrit in patients undergoing percutaneous coronary interventions.

Unlabelled: Essentials Platelet reactivity is correlated with thrombotic risk after percutaneous coronary intervention (PCI). Hematocrit (HCT) is associated with platelet reactivity as measured with the VerifyNow P2Y assay. We tested a formula proposed to correct VerifyNow measurements for HCT in 978 PCI patients.

Fibrin clot formation and fibrinolysis in patients with a history of coronary stent thrombosis.

Introduction: Coronary stent thrombosis is a devastating complication of percutaneous coronary intervention (PCI). Multiple factors underlie the pathophysiological mechanisms of stent thrombosis. Previous studies demonstrated that patients with stent thrombosis, compared to control PCI patients, formed denser fibrin clots in vitro which were more resistant to fibrinolysis, suggesting that altered fibrin clot properties may contribute to the pathophysiology of stent thrombosis.

The use of platelet reactivity testing in patients on antiplatelet therapy for prediction of bleeding events after cardiac surgery.

Many patients are treated with platelet inhibitors such as aspirin and clopidogrel for prevention of thrombotic cardiovascular events. However, the inhibitory effect of antiplatelet therapy is variable between patients; in some, the platelets are hardly inhibited, while in others, the platelets are excessively inhibited. The newer and more potent platelet inhibitors, prasugrel and ticagrelor, often lead to low platelet reactivity, which potentially leads to bleeding events.

The hypercoagulable profile of patients with stent thrombosis.

Objective: Coronary stent thrombosis is a devastating complication after percutaneous coronary intervention (PCI). The mechanisms underlying stent thrombosis are multifactorial. Whether the coagulation system is involved in the pathophysiology of stent thrombosis is unclear.

The use of platelet function testing in PCI and CABG patients.

Antiplatelet drugs are widely used in the treatment of patients with coronary artery disease. Dual anti-platelet therapy with acetylsalicylic acid (ASA) and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) is the recommended strategy for patients undergoing a percutaneous coronary intervention (PCI), while patients that undergo coronary artery bypass grafting (CABG) are treated with ASA monotherapy. However, the response to these drugs as assessed with platelet function tests varies between patients.

Towards personalized medicine based on platelet function testing for stent thrombosis patients.

Stent thrombosis (ST) is a severe and feared complication of coronary stenting. Patients who have suffered from ST are usually treated according to the "one-size-fits-all" dosing regimen of aspirin and clopidogrel. Many ST patients show high on-treatment platelet reactivity (HPR) despite this antiplatelet therapy (APT).

The influence of CYP2C19*2 and *17 on on-treatment platelet reactivity and bleeding events in patients undergoing elective coronary stenting.

Objectives: To investigate the impact of genotypes on the basis of the loss-of-function variant CYP2C19*2 and the gain-of-function variant CYP2C19*17 on on-treatment platelet reactivity and on the occurrence of Thrombolysis in Myocardial Infarction (TIMI) major bleedings in 820 clopidogrel-treated patients who underwent elective coronary stenting.

Methods: On-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. Postdischarge TIMI major bleedings within 1 year after enrollment were recorded.

Effect of gender difference on platelet reactivity.

Background: Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established.

Methods: On-treatment platelet reactivity was determined in 717 men and 234 women on dual antiplatelet therapy, undergoing elective coronary stent implantation.

The relationship between platelet reactivity and infarct-related artery patency in patients presenting with a ST-elevation myocardial infarction.

Both heightened platelet reactivity and an occluded infarct related artery (IRA) on initial angiography and at the time of primary percutaneous coronary intervention (PCI) are associated with a worsened clinical outcome in patients with ST-elevation myocardial infarction (STEMI). However, the relationship between platelet reactivity and IRA patency has not yet been established. Consecutive STEMI-patients were enrolled in this study.

A case-control study on platelet reactivity in patients with coronary stent thrombosis.

Background: The pathophysiology of stent thrombosis (ST) has evolved from the identification of single causative factors to a complex multifactorial model.

Objectives: The aim of the present study was to investigate whether patients with a history of ST exhibit heightened platelet reactivity to clopidogrel and aspirin.

Patients/methods: Pretreatment and on-treatment platelet reactivity to clopidogrel and aspirin, as well as dual antiplatelet therapy resistance, was determined in 84 patients with a history of definite ST (cases: 41 early ST; 43 late ST) and in 103 control patients with a previously implanted coronary stent but no ST after the index procedure.

Monitoring antiplatelet therapy with point-of-care platelet function assays: a review of the evidence.

Multiple studies have demonstrated that subgroups of patients receiving combination therapy with aspirin and clopidogrel fail to produce the anticipated antiplatelet effect, and various terms such as 'aspirin resistance', 'clopidogrel resistance', 'heightened post-treatment platelet reactivity' and 'residual platelet reactivity' have been introduced in the medical literature. Light transmittance aggregometry is generally considered to be the gold standard for determining platelet function, but its relevance to in vivo platelet function is questionable and the logistical demands of the method make it impossible to use in daily practice. The introduction of several point-of-care platelet function assays may be the key to the widespread clinical use of platelet function testing and may identify patients who are at risk for the occurrence of adverse cardiac events.