Dual Antiplatelet Therapy in Acute Ischemic Stroke: A 2-Time-Window Study of CYP2C19 Genotypes and Functional Outcomes.

CYP2C19

CYP2C19 loss-of-function alleles reduce clopidogrel bioactivation, and thus the antiplatelet effect expected from dual therapy.

This retrospective Taiwanese cohort linked a prospective stroke registry to the Taiwan Precision Medicine Initiative biobank in 741 patients with mild to moderate acute ischemic stroke (NIHSS ≤ 10), of whom 463 (62.5%) carried a CYP2C19 loss-of-function allele. Two windows were analysed: the acute window (first 48 hours, outcome at discharge) and the de-escalation window at discharge (outcome at 90 days). In the acute window, genotype was not associated with a favourable outcome, which was dominated by age and baseline NIHSS. In the de-escalation window, continuing aspirin plus clopidogrel at discharge was associated with a favourable 90-day outcome (OR 2.34; 95% CI 1.16-4.74; P = 0.018), an association driven by loss-of-function carriers (OR 2.74; 95% CI 1.17-6.38; P = 0.020). That association was nonetheless attenuated in propensity score-matched analyses, with no interaction between carrier status and dual antiplatelet therapy.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The result calls for caution: the attenuation after propensity score matching and, above all, the absence of a genotype × treatment interaction mean these data do not demonstrate a benefit specific to carriers. The authors say as much in calling for an adequately powered randomised trial. The solid contribution is a negative and useful one: in this cohort, CYP2C19 genotype did not predict early neurological deterioration.

Analysis by Dr Thibaut Benquey