TY - JOUR
T1 - Genotype-Phenotype Association and Impact on Outcomes following Guided De-Escalation of Anti-Platelet Treatment in Acute Coronary Syndrome Patients
T2 - The TROPICAL-ACS Genotyping Substudy
AU - Gross, Lisa
AU - Trenk, Dietmar
AU - Jacobshagen, Claudius
AU - Krieg, Anne
AU - Gawaz, Meinrad
AU - Massberg, Steffen
AU - Baylacher, Monika
AU - Aradi, Daniel
AU - Stimpfle, Fabian
AU - Hromek, Julia
AU - Vogelgesang, Anja
AU - Hadamitzky, Martin
AU - Sibbing, Dirk
AU - Geisler, Tobias
N1 - Publisher Copyright:
© 2018 Georg Thieme Verlag KG Stuttgart - New York.
PY - 2018
Y1 - 2018
N2 - Background Phenotype-guided de-escalation (PGDE) of P2Y 12 -inhibitor treatment with an early switch from prasugrel to clopidogrel was identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19 genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients treated with clopidogrel or prasugrel and thus might be useful for guidance of early de-escalation of anti-platelet treatment. Methods and Results A total of 603 ACS consecutive patients were enrolled in four centres (23.1% of the overall TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19∗2, ∗3 and ∗17 alleles was performed. Associations between PR and the primary and secondary endpoints of the TROPICAL-ACS trial and CYP2C19∗2 and CYP2C19∗17 carrier status were evaluated. For the PGDE group, the on-clopidogrel PR significantly differed across CYP2C19∗2 (p < 0.001) and CYP2C19∗17 genotypes (p = 0.05). Control group patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR versus non-high PR patients within the PGDE group, significant differences were observed for the rate of CYP2C19∗2 allele carriers (43% vs. 28%, p = 0.007). Conclusion CYP2C19∗2 and CYP2C19∗17 carrier status correlates with PR in ACS patients treated with clopidogrel and thus might be useful for pre-selecting patients who will and who may not be suitable for PGDE of anti-platelet treatment. Regarding phenotype-guided treatment, we did not observe added benefit of genotyping to predict ischaemic and bleeding risk in patients who underwent a PGDE approach. Clinical Trial Registration URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.
AB - Background Phenotype-guided de-escalation (PGDE) of P2Y 12 -inhibitor treatment with an early switch from prasugrel to clopidogrel was identified as an effective alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19 genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients treated with clopidogrel or prasugrel and thus might be useful for guidance of early de-escalation of anti-platelet treatment. Methods and Results A total of 603 ACS consecutive patients were enrolled in four centres (23.1% of the overall TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19∗2, ∗3 and ∗17 alleles was performed. Associations between PR and the primary and secondary endpoints of the TROPICAL-ACS trial and CYP2C19∗2 and CYP2C19∗17 carrier status were evaluated. For the PGDE group, the on-clopidogrel PR significantly differed across CYP2C19∗2 (p < 0.001) and CYP2C19∗17 genotypes (p = 0.05). Control group patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR versus non-high PR patients within the PGDE group, significant differences were observed for the rate of CYP2C19∗2 allele carriers (43% vs. 28%, p = 0.007). Conclusion CYP2C19∗2 and CYP2C19∗17 carrier status correlates with PR in ACS patients treated with clopidogrel and thus might be useful for pre-selecting patients who will and who may not be suitable for PGDE of anti-platelet treatment. Regarding phenotype-guided treatment, we did not observe added benefit of genotyping to predict ischaemic and bleeding risk in patients who underwent a PGDE approach. Clinical Trial Registration URL: https//www.clinicaltrials.gov. Unique Identifier: NCT: 01959451.
KW - acute coronary syndrome
KW - bleeding
KW - cytochrome P450 (CYP) 2C19
KW - genotyping
KW - platelets
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85053371066&partnerID=8YFLogxK
U2 - 10.1055/s-0038-1667337
DO - 10.1055/s-0038-1667337
M3 - Article
C2 - 30103241
AN - SCOPUS:85053371066
SN - 0340-6245
VL - 118
SP - 1656
EP - 1667
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 9
ER -