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.

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Key information

Conditions

Acute Coronary Syndrome Cardiovascular Diseases Heart Diseases Myocardial Ischemia Vascular Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Damanhour University

Damanhur, Beheira, 22511, Egypt

About this study

Ethical committee approval will be obtained from Ethics committee of Faculty of Pharmacy, Damanhour University.
All participants should agree to take part in this clinical study and will provide informed consent.
Over 100 patients diagnosed with acute coronary syndrome for whom bisoprolol therapy is prescribed , will be recruited from Alexandria university hospital.
whole blood samples will be collected for Analyses of CYP2D6 and CYP3A4 variant alleles.
Blood samples for plasma concentration measurements of bisoprolol will be drawn at steady-state peak levels after 2-4 hours of administration of bisoprolol.
Heart rate and blood pressure of the patients will be measured to assess the clinical effect of bisoprolol.
Echocardiogram will be obtained at baseline and after 1-3 months of therapy with bisoprolol to assess the effect of the drug on ventricular Remodeling.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Patients admitted with chest pain suspected to have ACS (acute coronary syndrome).
Both with ST elevation (STEMI) and without ST elevation (N-STEMI ) and unstable angina.
HR > 50 bpm.
Systolic Blood pressure > 90 mmHg.

Exclusion criteria

Patients with contraindications to Bisoprolol therapy:

Heart rate <60 bpm
Systolic blood pressure <90 mmHg
Moderate or severe left ventricular failure
Shock
heart block
Active asthma/reactive airways disease.

Treatment and study plan

Bisoprolol Fumarate

Drug

antihypertensive medicine prescribed for acute coronary syndrome patients

Other names: concor

Primary outcomes

CYP2D6 gene polymorphism

Time frame: 2 months

CYP2D6 gene polymorphism
CYP3A5 gene polymorphism

Time frame: 2 months

CYP3A5 gene polymorphism

Sponsors and collaborators

Lead sponsor

Damanhour University

Other

Collaborators

Alexandria University

Registry information

Important dates

Study start: 2021
Primary completion: 2022
Study completion: 2022
First posted: Sep 10, 2022
Registry last updated: Jun 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed