Key result
In STEMI patients treated with ticagrelor, CYP3A4*22 carrier status did not significantly affect the rate of thrombotic events compared to non-carriers (1.3% vs. 2.5%, adjusted HR 1.81).
Why the study?
The study was conducted to determine the clinical efficacy, adverse events, and side-effect dyspnea associated with CYP3A4*22 and CYP3A5 expressor status in ticagrelor-treated STEMI patients.
Does CYP3A4*22 carrier status or CYP3A5 expressor status affect thrombotic and bleeding event rates or dyspnea in STEMI patients treated with ticagrelor?
Cohort (n=1,281)
Open-label
Yes
Does CYP3A4*22 carrier status or CYP3A5 expressor status affect thrombotic and bleeding event rates or dyspnea in STEMI patients treated with ticagrelor?
Hazard Ratio: 1.81 (95% CI 0.43–7.62)
Absolute Event Rate: 1.3% vs 2.5%
p-value: p=0.42
In STEMI patients treated with ticagrelor, CYP3A4*22 carrier status and CYP3A5 expressor status did not significantly affect the rates of thrombotic events, bleeding, or dyspnea.
No impact of CYP3A4*22 or CYP3A5 status on ticagrelor outcomes or dyspnea; extends null pharmacogenetic findings to STEMI clinical events.
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.
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Azzahhafi et al. (2022) conducted a cohort in ST-segment elevation myocardial infarction (n=1,281). CYP3A4*22 carrier status vs. CYP3A4*22 non-carrier status was evaluated on Combined thrombotic endpoint (cardiovascular death, myocardial infarction, definite stent thrombosis and stroke) (adjusted HR 1.81, 95% CI 0.43-7.62, p=0.42). In STEMI patients treated with ticagrelor, CYP3A4*22 carrier status did not significantly affect the rate of thrombotic events compared to non-carriers (1.3% vs. 2.5%, adjusted HR 1.81).
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