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.
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