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Fulltext Aspirin resistance in patients with acute coronary events: risk factors and prevalence as determined by whole blood multiple electrode aggregometry

Ibrahim O, Maskon O, Darinah N, Raymond AA, Rahman MM

Pak J Med Sci, 2013 Nov;29(6):1319-22.
PMID: 24550945

OBJECTIVES: To determine the prevalence of aspirin resistance and associated risk factors based on biochemical parameters using whole blood multiple electrode aggregometry.
METHODS: The study was conducted at the outpatients cardiology clinic of the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from August 2011 to February 2012. Subjects on aspirin therapy were divided into two groups; first-ever coronary event and recurrent coronary event. Aspirin resistance was measured by a Multiplate(®) platelet analyser.
RESULTS: A total of 74 patients (63 male, 11 female), with a mean age of 57.93 ± 74.1years were enrolled in the study. The patients were divided into two groups -first-ever coronary event group (n=52) and recurrent coronary event group (n=22). Aspirin resistance was observed in 12 out of 74 (16%) of the study patients, which consisted of 11 patients from the first-ever coronary event group and one patient from the recurrent coronary event group. There were significant correlations between aspirin resistance and age (r = -0.627; p = 0.029), total cholesterol (r = 0.608; p = 0.036) and LDL (r = 0.694; p = 0.012). LDL was the main predictor for area under the curve (AUC) for aspirin resistance. However, there was no association between aspirin resistance and cardiovascular events in both groups in this study.
CONCLUSIONS: Aspirin resistance was observed in 16% of the study population. LDL was the major predictor of aspirin resistance. No association was found in the study between aspirin resistance with recurrent coronary events.
KEYWORDS: Aspirin resistance; Multiplate® platelet analyser; aspirin responsiveness; first-ever coronary event; recurrent coronary event
The Implication of the Polymorphisms of COX-1, UGT1A6, and CYP2C9 among Cardiovascular Disease (CVD) Patients Treated with Aspirin

Jalil NJ, Bannur Z, Derahman A, Maskon O, Darinah N, Hamidi H, et al.

J Pharm Pharm Sci, 2015;18(3):474-83.
PMID: 26517138

PURPOSE: Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated.
METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR).
RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033).
CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

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