Effect of Bruton's tyrosine kinase inhibitors on platelet aggregation in patients with acute myocardial infarction
| Autor: | Maria Bhatti, Tobias Geisler, Nicholas D. Gollop, Stuart A. Rushworth, Kristian M. Bowles, Alisdair Ryding, Marcus Flather, Olga Michail, Sarah Ayton |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Platelet Aggregation medicine.drug_class Myocardial Infarction 030204 cardiovascular system & hematology Pharmacology Tyrosine-kinase inhibitor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine P2Y12 Humans Medicine Bruton's tyrosine kinase Prospective Studies Myocardial infarction Protein Kinase Inhibitors Aspirin biology business.industry Hematology Middle Aged medicine.disease Clopidogrel chemistry 030220 oncology & carcinogenesis Ibrutinib Acute Disease biology.protein Female business Ticagrelor Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Thrombosis Research. 179:64-68 |
| ISSN: | 0049-3848 |
| Popis: | Aims: Despite widespread use of dual antiplatelet therapy in acute myocardial infarction, there remains a residual risk of morbidity and mortality. Bruton's Tyrosine Kinase inhibitors have been found to inhibit platelet aggregation through the Glycoprotein VI collagen-mediated pathway. The Bruton's Tyrosine Kinase inhibitor, Ibrutinib is used in the management of haematological malignancies and another Bruton's Tyrosine Kinase inhibitor, ONO-4059 (also known as tirabrutinib), is in clinical development. This is an observational study to evaluate the effects of Ibrutinib and ONO-4059 on platelet aggregation after acute myocardial infarction. Methods and results: Twenty patients with a confirmed diagnosis of acute myocardial infarction were enrolled and blood samples obtained within 48 h of hospital admission. All patients were on dual antiplatelet therapy; aspirin plus a P2Y12 inhibitor (clopidogrel or ticagrelor). Blood samples were treated ex vivo with increasing concentrations of Ibrutinib (0, 0.5, 1, 2 μM) and ONO-4059 (0, 0.2, 0.5, 1 μM). Platelet aggregation was measured in response to collagen using a Multiplate analyser to estimate the area under the curve, with lower values indicating lower platelet aggregation. The median age was 63 years and 80% were male. The median area under the curve values for Ibrutinib concentrations 0 (control), 0.5, 1 and 2 mmol/l were 18.5, 8 (P = 0.0004), 4.5 (P |
| Databáze: | OpenAIRE |
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