Pharmacogenetic CYP2C19 testing led to implemented therapy changes in 70.1% of patients with loss-of-function variants, which were associated with a non-significant increased risk of recurrent ischemic events (OR 2.2).
Observational (n=56)
Yes
Does pharmacogenetic testing for CYP2C19 lead to clinically relevant management changes in patients on clopidogrel therapy?
Pharmacogenetic testing for CYP2C19 in clinical practice identifies patients at elevated risk of ischemic events and successfully leads to the implementation of alternative antiplatelet therapies in the majority of affected patients.
Effect estimate: OR 2.2 (95% CI 0.3-14.4)
p-value: p=0.41
PURPOSE: The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. METHODS: We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. RESULTS: Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3-14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. CONCLUSION: PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.
Russmann et al. (Thu,) conducted a observational in Patients undergoing clopidogrel therapy (n=56). Pharmacogenetic CYP2C19 testing was evaluated on Association of CYP2C19 loss of function variants with recurrent thrombotic events during clopidogrel therapy (nested case-control primary outcome) (OR 2.2, 95% CI 0.3-14.4, p=0.41). Pharmacogenetic CYP2C19 testing led to implemented therapy changes in 70.1% of patients with loss-of-function variants, which were associated with a non-significant increased risk of recurrent ischemic events (OR 2.2).
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