Sex Differences in Prognostic Implications of CYP2C19 Genotype After Drug-Eluting Stent Implantation.

CYP2C19 loss-of-function alleles (intermediate/poor metabolizers) — significantly increased 5-year cardiovascular risk in men but not women

In the PTRG-DES consortium (4,630 East-Asian ACS patients post-drug-eluting stent), CYP2C19 intermediate/poor metabolizer status was a significant predictor of 5-year major adverse cardiovascular events in men (adjusted HR 3.27, 95%CI 1.58–6.74, p=0.001) and cardiac death (HR 7.01, p=0.002), but showed no significant association in women. The sex-by-CYP2C19 interaction was statistically significant for both endpoints. This sex-stratified finding has direct implications for genotype-guided antiplatelet therapy decisions.

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This sex-by-CYP2C19 genotype interaction is clinically significant: it suggests that preemptive genotyping recommendations for clopidogrel may need to be sex-stratified, at least in East-Asian populations. The underlying mechanism remains unclear — pharmacokinetic, hormonal, or body composition differences are plausible hypotheses. Replication in Caucasian populations is needed.

Clinical impact : 2/3 · Evidence strength : 3/3 · Novelty : 2/2 · Sample size : 1/1 · Journal quality : 1/1 → Total : 9/10