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23.06.2018 | Original Research Article | Ausgabe 7/2018 Open Access

Drugs & Aging 7/2018

Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel

Zeitschrift:
Drugs & Aging > Ausgabe 7/2018
Autoren:
Roberta Galeazzi, Fabiola Olivieri, Liana Spazzafumo, Giuseppina Rose, Alberto Montesanto, Simona Giovagnetti, Sara Cecchini, Gelsomina Malatesta, Raffaele Di Pillo, Roberto Antonicelli
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s40266-018-0555-1) contains supplementary material, which is available to authorized users.
Roberta Galeazzi, Fabiola Olivieri and Liana Spazzafumo contributed equally.

Abstract

Objective

The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants.

Methods

Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes.

Results

The poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099–1.45; χ2 = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033–1.67; χ2 = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers.

Conclusions

Our findings suggest that ACS patients classified as ‘poor or ultra-rapid’ metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.

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Zusatzmaterial
Supplementary Table 1 Phenotype metaboliser status according to CYP2C19 and ABCB1 genotypes (DOCX 18 kb)
40266_2018_555_MOESM1_ESM.docx
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