Effects of CYP2C19 genotypes on clopidogrel treatment in the CURE and ACTIVE trials. Guillaume Pare MD Canada Research Chair in Genetic and Molecular Epidemiology. Background.
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Effects of CYP2C19 genotypes on clopidogrel treatment in the CURE and ACTIVE trials
Guillaume Pare MD
Canada Research Chair in Genetic and Molecular Epidemiology
2 carrier status
- Loss-of-function carriers (1 or more *2, *3): 24%
- Gain-of-function carriers (1 or more *17): 41%
Yusuf et al. NEJM 2001; 345: 494-502
CURE Overall: 582 events, 9.3 % versus 719 events, 11.4%; HR=0.80 95% CI 0.72-0.90, P<0.001
CURE-Genetics: 231 events, 9.1% versus 316 events, 12.6%; HR=0.71 95% CI 0.60-0.84, P<0.001
Heterogeneity P-value = 0.12
Heterogeneity P-value = 0.29
Heterogeneity P-value = 0.64
No heterogeneity for the first primary (P=0.84), second primary (P=0.87) or safety (P=0.74) endpoint
Significant heterogeneity for the first (P=0.02) and second (P=0.03) primary endpoints.
No heterogeneity for the safety (P=0.66) endpoint.
ACTIVE Overall: 832 events, 22.1 % versus 924 events, 24.4%; HR=0.89 95% CI 0.81-0.98, P=0.01
ACTIVE-Genetics: 114 events, 20.0% versus 154 events, 26.3%; HR=0.74 95% CI 0.58-0.94, P=0.01
Connolly et al. NEJM 2009; 360: 2066-78
No heterogeneity for the primary (P=0.73) or safety (P=0.16) endpoints.
No heterogeneity for the primary (P=0.17) or safety (P=0.96) endpoints.
CURE/ACTIVE Genetics Team
With support from BMS and Sanofi