Pharmacogenetic Study of Bisoprolol in Egyptian Patients With Acute Coronary Syndrome

Acute coronary syndrome (ACS) is any group of clinical symptoms compatible with acute myocardial ischemia and includes unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI). (1). In Egypt, the overall prevalence of coronary heart disease (CHD) is 8.3 % (2). In addition, CHD in Egypt is the principal cause of death, responsible for 21.73% of total mortality (2).

Beta-blockers have shown to reduce the short-term risk of a reinfarction and the long-term risk of all-cause mortality and cardiovascular mortality (3). Beta blockers are used within 24 hours of ACS and given as long-term therapy after discharge (4). The Most frequently used drug in Egypt is bisoprolol.

In patients with myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous betablocker before reperfusion reduced infarct size and increased left ventricular ejection fraction (4). Despite the established benefits of beta blockers in ACS (acute coronary syndrome patients), they showed interindividual variability in patient's' blood pressure and heart rate (5).

pharmacokinetic variability was found in bisoprolol response especially in elderly patients (6). Bisoprolol is eliminated in equal parts by hepatic metabolism by CYP2D6 and CYP3A4 enzymes and by the kidney(7). A possible cause for this variability may be due to CYP450 genetic polymorphism. The CYP450 activity ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs) (8).The proposed research in this application will investigate the correlation between CYP2D6 and CYP3A4 polymorphism and pharmacokinetics of bisoprolol and will investigate the impact of the Genes' polymorphism on the clinical effect of bisoprolol in patients with acute coronary syndrome.