Aims: Clopidogrel is prescribed for the prevention of atherothrombotic events. While investigations have identified genetic determinants of inter-individual variability in on-treatment platelet inhibition (e.g. CYP2C19*2), evidence that these variants have clinical utility to predict major adverse cardiovascular events (CVEs) remains controversial.
Methods And Results: We assessed the impact of 31 candidate gene polymorphisms on adenosine diphosphate (ADP)-stimulated platelet reactivity in 3391 clopidogrel-treated coronary artery disease patients of the International Clopidogrel Pharmacogenomics Consortium (ICPC). The influence of these polymorphisms on CVEs was tested in 2134 ICPC patients (N = 129 events) in whom clinical event data were available. Several variants were associated with on-treatment ADP-stimulated platelet reactivity (CYP2C19*2, P = 8.8 × 10-54; CES1 G143E, P = 1.3 × 10-16; CYP2C19*17, P = 9.5 × 10-10; CYP2B6 1294 + 53 C > T, P = 3.0 × 10-4; CYP2B6 516 G > T, P = 1.0 × 10-3; CYP2C9*2, P = 1.2 × 10-3; and CYP2C9*3, P = 1.5 × 10-3). While no individual variant was associated with CVEs, generation of a pharmacogenomic polygenic response score (PgxRS) revealed that patients who carried a greater number of alleles that associated with increased on-treatment platelet reactivity were more likely to experience CVEs (β = 0.17, SE 0.06, P = 0.01) and cardiovascular-related death (β = 0.43, SE 0.16, P = 0.007). Patients who carried eight or more risk alleles were significantly more likely to experience CVEs [odds ratio (OR) = 1.78, 95% confidence interval (CI) 1.14-2.76, P = 0.01] and cardiovascular death (OR = 4.39, 95% CI 1.35-14.27, P = 0.01) compared to patients who carried six or fewer of these alleles.
Conclusion: Several polymorphisms impact clopidogrel response and PgxRS is a predictor of cardiovascular outcomes. Additional investigations that identify novel determinants of clopidogrel response and validating polygenic models may facilitate future precision medicine strategies.
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http://dx.doi.org/10.1093/ehjcvp/pvz045 | DOI Listing |
Cureus
December 2024
General Surgery, Sri Devaraj Urs Medical College, Kolar, IND.
Introduction Acute appendicitis is a common surgical emergency that requires a timely and accurate diagnosis to prevent complications. Several laboratory markers have been assessed to improve the diagnostic accuracy of acute appendicitis, including C-reactive protein (CRP), white blood cell (WBC) count, and cytokines like interleukins and tumor necrosis factor-alpha. One less commonly used but potentially valuable marker is the mean platelet volume (MPV), which indicates the size of circulating platelets and has the potential to serve as a biomarker for inflammatory conditions.
View Article and Find Full Text PDFFront Pediatr
December 2024
Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background: () is one of the most common pathogens of community-acquired pneumonia (CAP) in children. Although pneumonia (MPP) is considered a self-limiting disease, severe MPP (SMPP) occurs in some cases. This study aims to analyze clinical features of MPP and to explore predictive indicators in the early stage of infection.
View Article and Find Full Text PDFKawasaki disease (KD) is a leading cause of acquired heart disease in children, often resulting in coronary artery complications such as dilation, aneurysms, and stenosis. While intravenous immunoglobulin (IVIG) is effective in reducing immunologic inflammation, 10-15% of patients do not respond to initial therapy, and some show resistance even after two consecutive treatments. Predicting which patients will not respond to these two IVIG treatments is crucial for guiding treatment strategies and improving outcomes.
View Article and Find Full Text PDFCurr Eye Res
January 2025
Centre for Ophthalmology, Eberhard-Karls University, Tübingen, Germany.
Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.
Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.
ESMO Open
January 2025
Department of Medicine and DRCI, Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France.
Background: Paraneoplastic inflammatory syndrome (PIS) with fever and biological inflammation is a rare but severe condition often caused by the systemic production of interleukin 6 (IL-6) by cancer cells. We report on the efficacy of tocilizumab, an anti-IL-6 receptor antibody, in 35 patients with severe PIS.
Patients And Methods: All 35 patients with solid cancers (sarcomas, lung carcinoma, and breast carcinoma) diagnosed with a PIS from 2019 to 2024 treated with tocilizumab were analyzed in this single-center study (health authorities' approval R201-004-478).
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