TY - JOUR
T1 - CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients-Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study
AU - Bergmeijer, Thomas O
AU - Janssen, Paul W A
AU - Schipper, Jurjan C
AU - Qaderdan, Khalid
AU - Ishak, Maycel
AU - Ruitenbeek, Rianne S
AU - Asselbergs, Folkert W
AU - van 't Hof, Arnoud W J
AU - Dewilde, Willem J M
AU - Spanó, Fabrizio
AU - Herrman, Jean-Paul R
AU - Kelder, Johannes C
AU - Postma, Maarten J
AU - de Boer, Anthonius
AU - Deneer, Vera H M
AU - ten Berg, Jurriën M
PY - 2014/7
Y1 - 2014/7
N2 - RATIONALE: In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients.STUDY DESIGN: POPular Genetics (NCT01761786) is a randomized, open-label, multicenter trial involving 2,700 STEMI patients who undergo pPCI. Patients are randomized to CYP2C19 genotyping or routine ticagrelor or prasugrel treatment. In the genotyping group, *1/*1 (wild-type) patients receive clopidogrel, and patients carrying 1 or 2 *2 or *3 loss-of-function alleles receive ticagrelor or prasugrel. The primary net clinical benefit end point is the composite of death, (recurrent) myocardial infarction, definite stent thrombosis, stroke, and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding at 1 year. Primary safety end point is the composite of (PLATO) major and minor bleeding. Cost-effectiveness and quality of life will be assessed by calculating quality-adjusted life-years, net costs per life-year, and per quality-adjusted life-year gained.CONCLUSION: The POPular Genetics study is the first large-scale trial comparing CYP2C19 genotype-guided antiplatelet therapy to a nontailored strategy in terms of net clinical benefit, safety, and cost-effectiveness.
AB - RATIONALE: In patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI), the use of dual antiplatelet therapy is essential to prevent atherothrombotic complications. Therefore, patients are treated with acetylsalicylic acid and clopidogrel, prasugrel, or ticagrelor. Clopidogrel, however, shows a major interindividual variation in antiplatelet effect, which is correlated to an increase in atherothrombotic events in patients with high platelet reactivity. This interindividual variation is partly a result of CYP2C19 genetic variants. Ticagrelor and prasugrel reduce atherothrombotic events but increase bleeding rate and drug costs, as compared with clopidogrel. CYP2C19-based tailoring of antiplatelet therapy might be beneficial to STEMI patients.STUDY DESIGN: POPular Genetics (NCT01761786) is a randomized, open-label, multicenter trial involving 2,700 STEMI patients who undergo pPCI. Patients are randomized to CYP2C19 genotyping or routine ticagrelor or prasugrel treatment. In the genotyping group, *1/*1 (wild-type) patients receive clopidogrel, and patients carrying 1 or 2 *2 or *3 loss-of-function alleles receive ticagrelor or prasugrel. The primary net clinical benefit end point is the composite of death, (recurrent) myocardial infarction, definite stent thrombosis, stroke, and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding at 1 year. Primary safety end point is the composite of (PLATO) major and minor bleeding. Cost-effectiveness and quality of life will be assessed by calculating quality-adjusted life-years, net costs per life-year, and per quality-adjusted life-year gained.CONCLUSION: The POPular Genetics study is the first large-scale trial comparing CYP2C19 genotype-guided antiplatelet therapy to a nontailored strategy in terms of net clinical benefit, safety, and cost-effectiveness.
KW - Adult
KW - Aged
KW - Aryl Hydrocarbon Hydroxylases
KW - Cytochrome P-450 CYP2C19
KW - Electrocardiography
KW - Female
KW - Follow-Up Studies
KW - Genetic Techniques
KW - Genotype
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Infarction
KW - Percutaneous Coronary Intervention
KW - Platelet Aggregation Inhibitors
KW - Prospective Studies
KW - Ticlopidine
KW - Treatment Outcome
KW - Young Adult
U2 - 10.1016/j.ahj.2014.03.006
DO - 10.1016/j.ahj.2014.03.006
M3 - Article
C2 - 24952855
SN - 0002-8703
VL - 168
SP - 16-22.e1
JO - American Heart Journal
JF - American Heart Journal
IS - 1
ER -