Abstract
Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4. However, CYP2C19 genetic polymorphism, prominent in Malaysians, could influence target clopi-H4 plasma concentrations for clinical efficacy. This study addresses how inter-ethnicity variability within the Malaysian population impacts the attainment of clopi-H4 target plasma concentration under different CYP2C19 polymorphisms through pharmacokinetic (PK) modelling. We illustrated a statistically significant difference (P < 0.001) in the clopi-H4 Cmax between the extensive metabolisers (EM) and poor metabolisers (PM) phenotypes with either Malay or Malaysian Chinese population groups. Furthermore, the number of PM individuals with peak clopi-H4 concentrations below the minimum therapeutic level was partially recovered using a high-dose strategy (600 mg loading dose followed by a 150 mg maintenance dose), which resulted in an approximate 50% increase in subjects attaining the minimum clopi-H4 plasma concentration for a therapeutic effect.
Highlights
Malaysia is a multi-ethnic society with a population of over 32 million that is comprised of three predominant ethic groups, namely Malays (50.1%), Chinese (20.8%) and Indians (6.2%) [1]
The three largest population groups were selected for analysis and identified as Malay, Chinese and Indian, with Malay comprising the largest ethnic group contained within the National Cardiovascular Disease (NCVD) database (Table 1)
Given the unique ethnic diversity of the Malaysian population group, evidence-based approaches should account for the individual characteristics of patients rather than focusing on an average patient from a carefully selected patient population
Summary
Malaysia is a multi-ethnic society with a population of over 32 million that is comprised of three predominant ethic groups, namely Malays (50.1%), Chinese (20.8%) and Indians (6.2%) [1]. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for 22.6% and 26.4% of all hospital deaths annually in Ministry of Health Malaysia hospitals and Malaysian private hospitals, respectively [6]. Among those deaths, ischaemic heart disease accounts for the majority of all reported cardiovascular mortality, followed by acute myocardial infarction.
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