Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study

Jaouad Azzahhafi*, Thomas O. Bergmeijer, Wout W.A. van den Broek, Dean R.P.P. Chan Pin Yin, Senna Rayhi, Joyce Peper, Willem L. Bor, Daniel M.F. Claassens, Ron H.N. van Schaik, Jurriën M. ten Berg

*Corresponding author for this work

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Abstract

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients. Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43–7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58–1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39–2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73–1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45–2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27–1.30) p = 0.20]. Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01761786.

Original languageEnglish
Article number1032995
JournalFrontiers in Pharmacology
Volume13
DOIs
Publication statusPublished - 5 Dec 2022

Bibliographical note

Funding
This work was supported by grants from the Netherlands Organization for Health Research and Development (ZonMW).
The authors are solely responsible for designing and conducting this study, conducting all study analyses, and drafting and editing
the manuscript and its final contents.

Publisher Copyright:
Copyright © 2022 Azzahhafi, Bergmeijer, van den Broek, Chan Pin Yin, Rayhi, Peper, Bor, Claassens, van Schaik and ten Berg.

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