Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile

Summary

Several studies have shown that pharmacodynamic (PD) response varies between patients treated with clopidogrel and that individuals with reduced response have an increased risk of recurrent ischemic events, particularly in patients undergoing percutaneous coronary intervention. This is due to several factors influencing the response to clopidogrel, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. Loss of function (LOF) carriers of the CYP2C19 gene are associated with the decreased generation of the active metabolite clopidogrel and decreased platelet inhibition, which translates to an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Thus, drug regulatory authorities have cautioned about the decreased efficacy of clopidogrel among individuals with CYP2C19 LOF carriers and suggested using alternative therapies to inhibit p2Y12. Ticagrelor is a new generation P2Y12 receptor inhibitor with greater efficacy for PD and reduced rates of ischemic events compared with clopidogrel and are not affected by the CYP2C19 LOF polymorphism. However, in clinical practice, the genotype-guided selection strategy for the oral P2Y12 inhibitor has been limited despite intensive research efforts. This is due to the interaction of cardiovascular risk factors and molecular and biochemical complications that lead to poor response to platelet inhibitor therapy, which impedes physicians' ability to prescribe a more effective and personalized antiplatelet therapy. Therefore, we must move away from traditional approaches and use integrated systems biology study designs and disciplines to bridge the gap between genotype, phenotype, disease manifestation and/or recurrence. Pharmacometabolomics is a rapidly developing field that takes advantage of a systems pharmacology approach to probe the molecular pathways involved in drug response variability to understand metabolic changes and identify novel biomarkers that can be used to predict response more comprehensively. Using profiles of changes in metabolites can help establish drug exposure fingerprints and clarify the determinants of drug response. This study aims to investigate the Impact of pharmacogenetics-guided clopidogrel and ticagrelor treatment on platelet function test and its association with metabolomics in Coronary Artery Disease (CAD) patients undergoing PCI in Malaysia

Conditions

• Coronary Artery Disease (CAD)

Interventions

DRUG

Clopidogrel

Comparison of platelet reactivity between clopidogrel and ticagrelor

DRUG

Ticagrelor

Comparison of platelet reactivity between clopidogrel and ticagrelor

Sponsors & Collaborators

• Universiti Sains Malaysia

  lead OTHER

Principal Investigators

• Baharudin Ibrahim · Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Federal Territory Malaysia

• Nur Aizati Athirah Daud · School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia

• Mohammed Ahmed Akkaif · School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang 11800, Malaysia

• Muhammed Ali Sk Abdul Kader · Department of Cardiology, Penang General Hospital, Penang 10990, Malaysia

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-09-01

Primary Completion

2022-08-22

Completion

2022-08-22

FDA Drug

Yes

Countries

• Malaysia

Study Locations