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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1032995

DOI=10.3389/fphar.2022.1032995

ISSN=1663-9812

ABSTRACT=<p><bold>Aims:</bold> To determine the clinical efficacy, adverse events and side-effect dyspnea of <italic>CYP3A4*22</italic> and CYP3A5 expressor status in ticagrelor treated patients.</p><p><bold>Methods and results:</bold> Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for <italic>CYP3A4*22</italic> and <italic>CYP3A5*3</italic> alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. <italic>CYP3A4*22</italic> carriers (<italic>n</italic> = 152) <italic>versus CYP3A4*22</italic> non-carrier status (<italic>n</italic> = 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) <italic>p = 0.42</italic>], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58–1.50) <italic>p = 0.77</italic>]. Among the <italic>CYP3A4*1/*1</italic> patients, CYP3A5 expressors (<italic>n</italic> = 196) <italic>versus</italic> non-expressors (<italic>n</italic> = 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) <italic>p = 0.95</italic>], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73–1.76) <italic>p = 0.58</italic>]. With respect to dyspnea, no significant difference was observed between <italic>CYP3A4*22</italic> carriers <italic>versus CYP3A4*22</italic> non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45–2.42) <italic>p = 0.93</italic>], or in the <italic>CYP3A4*1/*1</italic> group, CYP3A5 expressors <italic>versus</italic> CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27–1.30) <italic>p = 0.20</italic>].</p><p><bold>Conclusion:</bold> In STEMI patients treated with ticagrelor, neither the <italic>CYP3A4*22</italic> carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, identifier NCT01761786.</p>