eTable 4. Main results and conclusions for clinical endpoints and stent thrombosis.
First authorref / Publication date / Model / Main result(95% CI) / Conclusion about the presence of association
Yes/no / Description (Abstract/Discussion)
Clinical endpoint
Hulot1 / July 2010 / Random
Fixed / 1.45 (1.12-1.89)
1.29 (1.12-1.49) / Possible / “[…] reduced CYP2C19 function appears to expose clopidogrel treated patients to excess cardiovascular risk and mortality. Conflicting results among studies may be explained by differences in types and/or levels of risk of patients.” (Abstract)
Jin2 / Sept 2010 / Random / 1.46 (1.01-2.13) / Yes / “CYP2C19*2 carrier status is significantly associated with an increased risk of adverse cardiovascular events.” (Abstract)
Mega4 / Oct 2010 / Random / 1.57 (1.13-2.16) / Possible / “Carriage of even one reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of MACE.” (Abstract)
Sofi3 / June 2011 / Random
Fixed / 1.96 (1.14-3.37)
1.33 (1.09-1.61) / Yes / “[…] the CYP2C19*2 polymorphism is associated with an increased risk of MACE and ST.” (Abstract)
Zabalza5 / June 2011 / Random / 1.23 (0.97-1.55) / No / “The results question the relevance of the CYP2C19 LOF alleles in the prediction of major cardiovascular events […].” (Abstract)
Liu7 / July 2011 / Random / 1.26 (1.06-1.50) / Yes / “[…] our analysis included more studies and more widely supported the conclusion that CYP2C19 loss-of-function alleles increase the rate of MACE and stent thrombosis.” (Letter)
Bauer6 / Aug 2011 / Random
Fixed / 1.11 (0.89-1.39)
1.07 (0.96-1.19) / No / “[…] does not indicate a substantial or consistent influence of CYP2C19 gene polymorphisms on the clinical efficacy of clopidogrel.” (Abstract)
Holmes11 / Dec 2011 / Random
Fixed / 1.34 (1.15-1.56)
1.18 (1.09-1.28) / No / “[…] overall there was no significant association of [the] genotype with cardiovascular events.” (Abstract)
Jang9 / May 2012 / Random / 1.42 (1.13-1.78) / Yes / “[…] carrier status for LOF CYP2C19 is associated with an increased risk of adverse clinical events in patients […].” (Abstract)
Singh8 / June 2012 / Random / 1.28 (1.07-1.55) / Yes / “[…] CYP2C19*2 polymorphism is associated with significantly increased adverse CV events.” (Abstract)
Yamaguchi10 / July 2012 / None / Not performed / No / “An association between the CYP2C19 polymorphism and clinical outcome was not observed […].” (Discussion)
Stent thrombosis
Hulot1 / July 2010 / Random
Fixed / 3.45 (2.13-5.57)
3.45 (2.14-5.57) / Yes / “The hazard of reduced-function CYP2C19 allele carriage was even more striking for ST […].” (Discussion)
Jin2 / Sept 2010 / Fixed / 3.81 (2.27-6.40) / Yes / “[…] We also noted a marked higher rate of ST in patients carrying at least one CYP2C19*2 allele.” (Discussion)
Mega4 / Oct 2010 / Random / 2.81 (1.81-4.37) / Yes / “Carriage of even one reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of MACE, particularly ST.” (Abstract)
Sofi3 / June 2011 / Fixed / 3.82 (2.23-6.54) / Yes / “[…] the CYP2C19*2 polymorphism is associated with an increased risk of MACE and ST.” (Abstract)
Zabalza5 / June 2011 / Random / 2.24 (1.52-3.30) / Yes / “The results question the relevance of the CYP2C19 LOF alleles in the prediction of major cardiovascular events beyond ST […].” (Abstract)
Liu7 / July 2011 / Random / 2.58 (1.77-3.77) / Yes / “ […] our analysis included more studies and more widely supported the conclusion that CYP2C19 loss-of-function alleles increase the rate of MACE and stent thrombosis.” (Letter)
Bauer6 / Aug 2011 / Random
Fixed / 1.77 (1.31-2.40)
1.67 (1.34-2.08) / No / “Specifically, the association of ST with LOF genotypes was subject to bias from small study effects and to interaction with publication year. Adjustment for these quality modifiers tended to abolish the association.” (Discussion)
Holmes11 / Dec 2011 / Random
Fixed / 1.88 (1.46-2.41)
1.75 (1.50-2.03) / Possible / “This […] meta-analysis does not demonstrate a clinically important association […] with the possible exception of ST.” (Discussion)
Jang9 / May 2012 / Fixed / 2.41 (1.76-3.30) / Yes / “[…] carriers of ≥1 CYP2C19 LOF allele have two times greater mortality and ST compared to wild-type homozygote carriers.” (Discussion)
Singh8 / June 2012 / Fixed / 2.41 (1.70-3.41) / Yes / “Our meta-analyses indicates that CYP2C19*2 polymorphism results in significantly increased risk of cardiovascular events like MI, ST and CV deaths.”(Discussion)
Yamaguchi10 / July 2012 / Fixed / 2.65 (1.46-4.84) / Yes / “[…] CYP2C19*2 carrier status was associated with ST only.” (Discussion)
Abbreviations: CI, confidence interval; ST, stent thrombosis; LOF, loss-of-function; MACE, major adverse cardiovascular event;
Model indicates whether effect estimates were obtained using random or fixed effect models. Main results are odds ratios or hazard ratio according to each of the meta-analyses.