Pharmacogenetic Study of Bisoprolol in Egyptian Patients With Acute Coronary Syndrome
Status:
Completed
Trial end date:
2022-08-16
Target enrollment:
Participant gender:
Summary
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.