Dual antiplatelet therapy, which consists of aspirin and a P2Y12 receptor inhibitor, is recommended for patients with acute coronary syndrome and for those undergoing coronary artery stent implantation to prevent cardiac events related to blood clot formation. Clopidogrel is the most frequently used P2Y12 inhibitor. However, unlike ticagrelor, which is immediately active upon administration, both prasugrel and clopidogrel require metabolic activation to inhibit platelet aggregation effectively. This metabolic process is dependent on several hepatic enzymes, including CYP2C19, CYP3A4/5, CYP2B6, CYP2C9, and CYP1A2. Notably, mutations in the CYP2C19 gene can lead to a loss of enzymatic function, thereby reducing the metabolism of clopidogrel. This reduction in metabolism can result in decreased effectiveness of clopidogrel in inhibiting platelet aggregation, which may be associated with adverse cardiovascular outcomes, including stent thrombosis. CYP2C19 is identified as the critical enzyme in the metabolism of clopidogrel1. Furthermore, a high prevalence of mutations in this enzyme has been reported in the Asian population, affecting up to 60% of individuals2. This diminished platelet inhibition manifests as high platelet reactivity (HPR) in platelet function tests. On the contrary, low platelet reactivity (LPR) or an excessive response to antiplatelet therapy increases the risk of bleeding complications. Therefore, optimizing platelet reactivity is crucial within the therapeutic window. To address this, we conducted research to assess platelet reactivity in Vietnamese patients with coronary artery disease who were receiving dual antiplatelet therapy with aspirin and clopidogrel.

Figure 1

Abbreviations: CAD: coronary artery disease; PCI: percutaneous coronary intervention; CABG: coronary artery bypass graft

The inclusion criteria targeted patients receiving treatment within the Interventional Cardiology Department at Cho Ray Hospital for coronary artery disease that required dual antiplatelet therapy. This therapy consisted of Aspirin at a minimum dosage of 162 mg at least 3 hours prior to testing or 81 mg for at least 5 days before testing, coupled with Clopidogrel administered at a minimum dosage of 300 mg at least 3 hours prior to testing or 75 mg for at least 5 days before testing. The exclusion criteria eliminated patients with a history of myocardial infarction (MI) or prior coronary artery interventions, patients who experienced bleeding events or mortality, and those not consenting to participate in the study.

Prior to undergoing cardiac catheterization and percutaneous coronary intervention, 4ml of the patient's blood was collected into anticoagulant tubes. These tubes were then incubated at room temperature for 10 minutes before undergoing platelet reactivity testing utilizing an aspirin-specific (ARU test) and a clopidogrel-specific (PRU test) kit. Results from the platelet reactivity tests were documented for each participant.

Considered variables include Age, Gender, BMI, Hypertension (HTN), Smoking status (SM), Diabetes Mellitus (DM), Dyslipidemia (DL), Heart failure, and platelet reactivity to Aspirin (ARU) and Clopidogrel (PRU), with cutoff points established at 550 for high aspirin platelet reactivity and 208 for high clopidogrel platelet reactivity. The cutoff for low clopidogrel platelet reactivity is set at 95.

Data analysis was executed using SPSS 20 software, with results presented as mean values (± standard deviation) or median (interquartile range), and as percentages (%).

Table 1

Characteristics	Frequency (Percentage)
Age (Mean ± SD)	65.7 (±9.9)
Gender Male	34 (62%)
Weight (Mean ± SD)	60.6 (±1.3)
Hypertension	49 (89%)
Diabetes Mellitus	10 (18%)
Smoking	36 (65%)
Dyslipidemia	53 (96%)
Heart Failure	12 (22%)
Clinical Presentation
Unstable Angina	17 (31%)
Non-ST Elevation MI	3 (5%)
ST Elevation MI	16 (29%)
Non-Fatal MI	19 (35%)

Table 2

	Sample	Male	Female	p
	(mean ± SD)
Age	65.7 ± 9.91	63.5 ± 8.7	69.1 ± 11	0.039

Table 3

	Sample	Male	Female	p
	(mean ± SD)
BMI (kg/m2)	23.2 ± 2.9	23.6 ± 3.2	22.4 ± 2.2	0.13

Figure 2

Abbreviation: PRU: platelet reactivity unit

In terms of platelet reactivity, measured by platelet reactivity unit (PRU) and aspirin reaction unit (ARU), the PRU levels varied between 7 and 282, with a median of 167, whereas ARU levels ranged from 350 to 650, with a median of 465 (Table 4). Clopidogrel response categorization using predefined cutoffs showed that 25.5% of the patients exhibited high PRU levels (≥ 208), 58.2% were within the therapeutic range (95-208), and 16.4% had low PRU levels (< 95) (Table 5 ). For aspirin, based on the cutoffs for classifying PRU levels, high (>550) and within therapeutic range (< 550), the distributions were 7.2% and 92.9%, respectively.

An analysis of the clinical characteristics among patients exhibiting high PRU levels on clopidogrel, indicative of suboptimal drug response, revealed a significantly lower mean age (p < 0.001) and an increased prevalence of type 2 diabetes mellitus (p = 0.048) in comparison with patients achieving therapeutic PRU levels (Table 6).

ARU: Aspirin Reaction Unit, COMMIT: ClOpidogrel and Metoprolol in Myocardial Infarction Trial, CYP1A2: Designations for specific cytochrome P450 enzyme involved in drug metabolism, CYP2B6: Designations for specific cytochrome P450 enzyme involved in drug metabolism, CYP2C19: Designations for specific cytochrome P450 enzyme involved in drug metabolism, CYP2C9: Designations for specific cytochrome P450 enzyme involved in drug metabolism, CYP3A4/5: Designations for specific cytochrome P450 enzymes involved in drug metabolism, DAPT: Dual Antiplatelet Therapy, DL: Dyslipidemia, DM: Diabetes Mellitus, HFpEF: Heart Failure with Preserved Ejection Fraction, HTN: Hypertension, LTA: Light Transmission Aggregometry, MI: Myocardial Infarction, NCEP (ATP III): National Cholesterol Education Program (Adult Treatment Panel III), PR: Platelet Reactivity, PRU: P2Y12 Reaction Unit, SM: Smoking, SPSS: Statistical Package for the Social Sciences

Phan Thi Bach Tuyet, RN (Cho Ray hospital) was involved in performing the tests.

Nghia T N, MD: Conceptualization; Writing - original draft; Critical Review. My H T N, MD: Formal analysis; Writing - original draft; Manuscrift editing; Critical Review. All authors read and approved the final manuscript.

None.

Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

This study was conducted in accordance with the amended Declaration of Helsinki. The institutional review board approved the study, and all participants provided written informed consent.

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The authors declare that they have no competing interests.