TY - JOUR
T1 - Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients
AU - Azzahhafi, Jaouad
AU - van den Broek, Wout W.A.
AU - Chan Pin Yin, Dean R.P.P.
AU - van der Sangen, Niels M.R.
AU - Sivanesan, Shabiga
AU - Bofarid, Salahodin
AU - Peper, Joyce
AU - Claassens, Daniel M.F.
AU - Janssen, Paul W.A.
AU - Harmsze, Ankie M.
AU - Walhout, Ronald J.
AU - Tjon Joe Gin, Melvyn
AU - Nicastia, Deborah M.
AU - Langerveld, Jorina
AU - Vlachojannis, Georgios J.
AU - van Bommel, Rutger J.
AU - Appelman, Yolande
AU - van Schaik, Ron H.N.
AU - Henriques, José P.S.
AU - Kikkert, Wouter J.
AU - ten Berg, Jurriën M.
N1 - Publisher Copyright:
© 2024 American College of Cardiology Foundation
PY - 2024/9/9
Y1 - 2024/9/9
N2 - Background: CYP2C19 genotype–guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). Objectives: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. Methods: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. Results: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). Conclusions: The implementation of a CYP2C19 genotype–guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.
AB - Background: CYP2C19 genotype–guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). Objectives: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. Methods: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. Results: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). Conclusions: The implementation of a CYP2C19 genotype–guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.
KW - acute coronary syndrome(s)
KW - CYP2C19
KW - dual antiplatelet therapy
KW - genotype-guided therapy
UR - http://www.scopus.com/inward/record.url?scp=85204544372&partnerID=8YFLogxK
U2 - 10.1016/j.jcin.2024.06.020
DO - 10.1016/j.jcin.2024.06.020
M3 - Article
C2 - 39217531
AN - SCOPUS:85204544372
SN - 1936-8798
VL - 17
SP - 1996
EP - 2007
JO - JACC: Cardiovascular Interventions
JF - JACC: Cardiovascular Interventions
IS - 17
ER -