Persistent Tic Disorders Are Associated With 17q12 Duplications.

Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are childhood-onset neuropsychiatric conditions with high heritability. Due to current sample size limitations, identifying TS/PTD risk genes has been challenging. This study addressed this issue by conducting a meta-analysis of microarray copy number variant (CNV) studies from three TS/PTD genomics consortia, supplemented with new data from 3,291 cases.

Impact of Race on Profiles of Platelet Reactivity and Clinical Outcomes in Clopidogrel-Treated Participants.

Black individuals undergoing percutaneous coronary intervention (PCI) experience higher rates of major adverse cardiovascular events (MACE) than non-Black individuals. This study assessed the racial differences in platelet reactivity and clinical outcomes among clopidogrel-treated participants. Two cohorts were analyzed.

Severe tirofiban-induced thrombocytopenia following percutaneous coronary intervention.

Unlabelled: Tirofiban is an intravenous glycoprotein IIb/IIIa inhibitor (GPI) that can be used as a bailout strategy in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with high thrombus burden. A rare complication of this agent is severe thrombocytopenia, with an incidence ranging from 0.1 % to 0.

Phenotype, P2Y Inhibitor Selection, and Clinical Outcomes in Patients on Maintenance Clopidogrel Therapy.

Background: Use of genotyping to guide antiplatelet therapy is associated with improved clinical outcomes in patients naïve to P2Y inhibitors undergoing percutaneous coronary intervention. The relationship between genotype and clinical outcomes in patients on maintenance clopidogrel at the time of percutaneous coronary intervention is unknown.

Methods: This was a retrospective, multicenter cohort study.

Switching Platelet P2Y Receptor Inhibiting Therapies.

Antiplatelet therapy involving aspirin and a P2Y receptor inhibitor is fundamental in managing patients with atherothrombotic disease. Switching between P2Y inhibitors is frequently observed in clinical settings for various reasons, such as safety, efficacy, patient adherence, or cost concerns. Although it occurs often, the optimal method for switching remains a concern owing to potential drug interactions, which can result in either inadequate platelet inhibition and subsequent thrombotic events or low platelet reactivity and increased bleeding risks due to therapy overlap.

International Consensus Statement on Platelet Function and Genetic Testing in Percutaneous Coronary Intervention: 2024 Update.

Current evidence indicates that dual antiplatelet therapy with aspirin plus a P2Y inhibitor is essential for the prevention of thrombotic events after percutaneous coronary interventions. However, dual antiplatelet therapy is associated with increased bleeding which may outweigh the benefits. This has set the foundations for customizing antiplatelet treatments to the individual patient.

Clopidogrel-Mediated P2Y Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD.

This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite.

Precision Antiplatelet Therapy after Percutaneous Coronary Intervention (Precision PCI) Registry - Informing optimal antiplatelet strategies.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) is indicated after percutaneous coronary intervention (PCI) to reduce the risk of atherothrombotic events. Approximately 30% of the US population has a CYP2C19 no-function allele that reduces the effectiveness of clopidogrel, but not prasugrel or ticagrelor, after PCI. We have shown improved outcomes with the integration of CYP2C19 genotyping into clinical care to guide the selection of prasugrel or ticagrelor in CYP2C19 no-function allele carriers.

Evaluating the Effect of Estimating Renal Function With the CKD-EPI 2021 Equation on the ABCD-GENE Score for Clopidogrel Response Prediction.

The ABCD-GENE score was developed to predict poor response to clopidogrel and includes Age, Body mass index, Chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m), Diabetes, and CYP2C19 GENE variants; a score ≥ 10 is predictive of reduced clopidogrel effectiveness after percutaneous coronary intervention (PCI). Estimation of GFR without a race variable via the CKD-EPI Scr 2021 equation is now recommended.

Genotype Is Associated With Adverse Cardiovascular Outcomes in Black Patients Treated With Clopidogrel Undergoing Percutaneous Coronary Intervention.

Background: Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.

Comparative effects of different antiplatelet strategies in carriers of CYP2C19 loss-of-function alleles: a network meta-analysis.

Background: Carriers of cytochrome 2C19 (CYP2C19) loss-of-function (LoF) alleles treated with clopidogrel have impaired drug metabolism, resulting in reduced active metabolite levels, high platelet reactivity (HPR), and an increased risk of thrombotic events. Several alternative antiplatelet therapies have been proposed to overcome HPR in these patients, but their comparative effects remain poorly explored.

Methods: Randomized controlled trials (RCTs) comparing different oral antiplatelet therapies in carriers of CYP2C19 LoF alleles undergoing percutaneous coronary interventions (PCI) were included.

Effectiveness of Clopidogrel vs Alternative P2Y Inhibitors Based on the ABCD-GENE Score.

Background: An ABCD-GENE (age, body mass index, chronic kidney disease, diabetes, and CYP2C19 genetic variants) score ≥10 predicts reduced clopidogrel effectiveness, but its association with response to alternative therapy remains unclear.

Objectives: The aim of this study was to evaluate the association between ABCD-GENE score and the effectiveness of clopidogrel vs alternative P2Y inhibitor (prasugrel or ticagrelor) therapy after percutaneous coronary intervention (PCI).

Methods: A total of 4,335 patients who underwent PCI, CYP2C19 genotyping, and P2Y inhibitor treatment were included.

P2Y Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

Background: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel.

Objectives: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score.

Bivalirudin in acute coronary syndromes.

Introduction: Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

Areas Covered: Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients.

Effect of lipid-lowering therapy on platelet reactivity in patients treated with and without antiplatelet therapy.

Circulating lipoproteins may interact with platelets, increasing platelet sensitivity to aggregating agonists and their tendency towards activation and thrombus formation. In particular, patients with hypercholesterolemia exhibit a higher degree of platelet reactivity compared to normolipidemic. Moreover, accruing evidence report that lipid-lowering therapies can reduce thrombus formation, particularly in the absence of concomitant antiplatelet therapy.

Switching From Cangrelor to Prasugrel in Patients Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet-6 (SWAP-6) Study.

Background: A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y inhibition with cangrelor to oral P2Y inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI).

Objectives: This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients.

Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial.

Background: Thrombo-inflammation is central to COVID-19-associated coagulopathy. TF (tissue factor), a driver of disordered coagulation and inflammation in viral infections, may be a therapeutic target in COVID-19. The safety and efficacy of the novel TF inhibitor rNAPc2 (recombinant nematode anticoagulation protein c2) in COVID-19 are unknown.