Impact of CYP2C19 genotyping on clopidogrel therapy adjustments in patients with stroke or TIA

Clopidogrel is an antiplatelet medication routinely used for the prevention of stroke. However, patients with impaired cytochrome P450 (CYP)2C19 enzyme activity exhibit lower levels of the active clopidogrel metabolite, resulting in reduced therapeutic response. At the Elisabeth-TweeSteden Hospital (ETZ), all patients receiving clopidogrel for stroke prevention undergo CYP2C19 genotyping. The aim of this study was to determine the prevalence of CYP2C19 genotypes and phenotypes among patients with (recurrent) stroke or TIA and to investigate whether genotyping results influenced clopidogrel therapy or other concomitant medications.

In this retrospective study, all patients genotyped for CYP2C19 between June 2020 and October 2020 and treated with clopidogrel for stroke prevention were included. Genotyping was performed for the CYP2C19 *2, *3 and *17 alleles. Data were collected on CYP2C19 genotype and phenotype, the indication for clopidogrel, and any therapy adjustments made. Results are presented as proportions (%).

Between June and October 2020, 382 patients with stroke were genotyped for CYP2C19. Phenotypes included the following: extensive metabolisers 64.7% (n=247), intermediate 26.9% (n=103), poor 5.0% (n=19), and ultra-rapid 3.4% (n=13). In patients with impaired metabolism (intermediate metabolisers and poor metabolisers), therapy was adjusted in 94.2% of cases. Among intermediate metabolisers, 68.0% were switched to acetylsalicylic acid (ASA)/dipyridamole, 20.4% to double-dose clopidogrel, 3.9% to ASA monotherapy, and 1.9% to other therapies. For poor metabolisers, 89.2% received ASA/dipyridamole, 5.3% ASA monotherapy and 5.3% other therapies. The phenotypes did not differ between first and recurrent strokes. Additional gene-drug interactions were seen, especially with proton pump inhibitors and antidepressants.

In the ETZ cohort, 31.9% of genotyped patients (26.9% intermediate metabolisers and 5% poor metabolisers) had impaired CYP2C19 metabolism. Genotype and phenotype information led to changes in clopidogrel therapy in nearly all of these patients, with the most common adjustment being a switch to ASA and dipyridamole combination therapy.