Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Background: Diabetes and CYP2C19 loss of function (LOF) alleles are associated with variable antiplatelet activity of the prodrug clopidogrel. Objective: We conducted the current observational trial (NCT03613857) to compare the combined and individualized effects of diabetes and CYP2C19 polymorphisms on the recurrence of ACS and anti-platelet activity of clopidogrelvsticagrelor in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Patients and interventions: Patients (948, 1 year follow-up 943) were randomly allocated in a 1:1 ratio to receive either clopidogrel or ticagrelor; following PCI; patients were sub-divided into eight groups according to the diabetes and/or CYP2C19 allele statusOutcome measures: The study 1ryoutcome was the recurrent ACS, whereas high platelet reactivity index (PRI),maximum platelet aggregation (MPA) and incidence of major bleeding events were considered the 2ryoutcomes. Results: Diabetic patients with LOF alleles taking clopidogrel had the highest recurrent ACS rate (6 out of 33 patients) vs all study groups (p<0.05). However, both drugs had equally prevented recurrent ACS in all other groups.Similarly,high PRI/MPA was significantly higher in the diabetic patients having LOF alleles and receiving clopidogrelvs ticagrelor group. Nevertheless, ticagrelor caused higher rates of major bleeding vsclopidogrel (p<0.001), and this necessitates. Indeed, the presence of either diabetes or LOF (+) alone had milder impact on the primary and secondary outcomes,respectively

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