Naveen L Pereira1, Charanjit Rihal2, Ryan Lennon3, Gil Marcus4, Sanskriti Shrivastava2, Malcolm R Bell2, Derek So5, Nancy Geller6, Shaun G Goodman7, Ahmed Hasan6, Amir Lerman2, Yves Rosenberg6, Kent Bailey3, M Hassan Murad8, Michael E Farkouh4. 1. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address: pereira.naveen@mayo.edu. 2. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. 3. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. 4. Peter Munk Cardiac Centre and Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada. 5. University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 6. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 7. St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada. 8. Evidence-Based Practice Center, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
OBJECTIVES: The aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel. BACKGROUND: The effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear. METHODS: Databases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype. RESULTS: Of 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction <0.001). CONCLUSIONS: The effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y12 inhibitor therapy.
OBJECTIVES: The aim of this study was to examine the effect of CYP2C19 genotype on clinical outcomes in patients with coronary artery disease (CAD) who predominantly underwent percutaneous coronary intervention (PCI), comparing those treated with ticagrelor or prasugrel versus clopidogrel. BACKGROUND: The effect of CYP2C19 genotype on treatment outcomes with ticagrelor or prasugrel compared with clopidogrel is unclear. METHODS: Databases through February 19, 2020, were searched for studies reporting the effect of CYP2C19 genotype on ischemic outcomes during ticagrelor or prasugrel versus clopidogrel treatment. Study eligibility required outcomes reported for CYP2C19 genotype status and clopidogrel and alternative P2Y12 inhibitors in patients with CAD with at least 50% undergoing PCI. The primary analysis consisted of randomized controlled trials (RCTs). A secondary analysis was conducted by adding non-RCTs to the primary analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia. Meta-analysis was conducted to compare the 2 drug regimens and test interaction with CYP2C19 genotype. RESULTS: Of 1,335 studies identified, 7 RCTs were included (15,949 patients, mean age 62 years; 77% had PCI, 98% had acute coronary syndromes). Statistical heterogeneity was minimal, and risk for bias was low. Ticagrelor and prasugrel compared with clopidogrel resulted in a significant reduction in ischemic events (relative risk: 0.70; 95% confidence interval: 0.59 to 0.83) in CYP2C19 loss-of-function carriers but not in noncarriers (relative risk: 1.0; 95% confidence interval: 0.80 to 1.25). The test of interaction on the basis of CYP2C19 genotype status was statistically significant (p = 0.013), suggesting that CYP2C19 genotype modified the effect. An additional 4 observational studies were found, and adding them to the analysis provided the same conclusions (p value of the test of interaction <0.001). CONCLUSIONS: The effect of ticagrelor or prasugrel compared with clopidogrel in reducing ischemic events in patients with CAD who predominantly undergo PCI is based primarily on the presence of CYP2C19 loss-of-function carrier status. These results support genetic testing prior to prescribing P2Y12 inhibitor therapy.
Authors: Vibhu Parcha; Brittain F Heindl; Peng Li; Rajat Kalra; Nita A Limdi; Naveen L Pereira; Garima Arora; Pankaj Arora Journal: Circ Genom Precis Med Date: 2021-10-21
Authors: Lindsay Ratner; Jing 'Daisy' Zhu; Megan N Gower; Tejendra Patel; Jordan A Miller; Amber Cipriani; George A Stouffer; Daniel J Crona; Craig R Lee Journal: Pharmacogenomics Date: 2022-01-27 Impact factor: 2.638
Authors: Jasmine A Luzum; Natasha Petry; Annette K Taylor; Sara L Van Driest; Henry M Dunnenberger; Larisa H Cavallari Journal: Clin Pharmacol Ther Date: 2021-07-07 Impact factor: 6.903
Authors: Davide Capodanno; Dominick J Angiolillo; Ryan J Lennon; Shaun G Goodman; Sang-Wook Kim; Fearghas O'Cochlain; Derek Y So; John Sweeney; Charanjit S Rihal; Michael Farkouh; Naveen L Pereira Journal: J Am Heart Assoc Date: 2022-02-08 Impact factor: 6.106
Authors: Amber L Beitelshees; Cameron D Thomas; Philip E Empey; George A Stouffer; Dominick J Angiolillo; Francesco Franchi; Sony Tuteja; Nita A Limdi; James C Lee; Julio D Duarte; Rolf P Kreutz; Todd C Skaar; James C Coons; Jay Giri; Caitrin W McDonough; Rachel Rowland; James M Stevenson; Thuy Thai; Mark R Vesely; Jacob T Wellen; Julie A Johnson; Almut G Winterstein; Larisa H Cavallari; Craig R Lee Journal: J Am Heart Assoc Date: 2022-02-12 Impact factor: 6.106
Authors: Brian Wood; Craig R Lee; Ian R Mulrenin; Megan N Gower; Joseph S Rossi; Karen E Weck; George A Stouffer Journal: Pharmacotherapy Date: 2021-07-21 Impact factor: 6.251