DataSheet1_Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study.pdf

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.

研究目的：旨在评估CYP3A4*22和CYP3A5表达状态在替格瑞洛治疗患者中的临床疗效、不良事件及呼吸困难副作用。研究方法与结果：POPular Genetics随机对照试验中的替格瑞洛治疗患者接受了CYP3A4*22和CYP3A5*3等位基因的分型。患者根据其基因型进行分组。共纳入了1,281名ST段抬高型心肌梗死（STEMI）患者。结果显示，CYP3A4*22携带者（n = 152）与CYP3A4*22非携带者状态（n = 1,129）在主要血栓终点（心血管死亡、心肌梗死、确定性的支架血栓形成和中风）[1.3% vs. 2.5%，调整后的风险比1.81（95%置信区间0.43–7.62）p = 0.42]或主要出血终点（PLATO主要和轻微出血）[13.2% vs. 11.3%，调整后的风险比0.93（95%置信区间0.58–1.50）p = 0.77]方面并无显著相关性。在CYP3A4*1/*1患者中，CYP3A5表达者（n = 196）与非表达者（n = 926）在主要血栓终点[2.6% vs. 2.5%，调整后的风险比1.03（95%置信区间0.39–2.71）p = 0.95]或主要出血终点[12.8% vs. 10.9%，调整后的风险比1.13（95%置信区间0.73–1.76）p = 0.58]方面亦未发现显著差异。至于呼吸困难，CYP3A4*22携带者与CYP3A4*22非携带者之间[44.0% vs. 45.0%，比值比1.04（95%置信区间0.45–2.42）p = 0.93]，或CYP3A4*1/*1组中CYP3A5表达者与CYP3A5非表达者之间[35.3% vs. 47.8%，比值比0.60（95%置信区间0.27–1.30）p = 0.20]，均未观察到显著差异。结论：在替格瑞洛治疗STEMI患者中，CYP3A4*22携带者状态和CYP3A5表达状态均未对血栓和出血事件发生率以及呼吸困难产生统计学上的显著影响。临床试验注册：ClinicalTrials.gov，注册号NCT01761786。