Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome

Summary

Our aim was to demonstrate that the sequential use of the Verigene^® rapid CYP2C19 test for genetic profiling and the VerifyNow^TM bedside test for platelet function measurement in ACS patients may optimise P2Y₁₂ inhibition. “Rapid” (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and “slow” metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU< 30) on prasugrel or high platelet reactivity (> 208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of “rapid” metabolisers on 75 mg of clopidogrel within 30–208 (PRU) of P2Y₁₂ inhibition is non-inferior to “slow” metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of “rapid” and “slow” metabolisers within 30–208 PRU of P2Y₁₂ inhibition was 71 % and 56.9 %, respectively, an absolute difference of +14.1 % (95 % CI, –0.05 % to 28.28 %) with a non-inferiority margin greater than the predefined margin of –10 %. Among patients out of target, all but one “slow” metabolisers displayed low-on prasugrel platelet reactivity while the majority of “rapid” metabolisers (68 %) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30–208 PRU of P2Y₁₂ inhibition was 83.6 % and 79.3 % in “rapid” and “slow” metabolisers, respectively (+4.3 %, 95 % CI –7.3 % to 15.9 %). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.

Keywords

Platelet pharmacology - atherothrombosis - clinical trials - antiplatelet drugs - pharmacodynamics

• References

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