Platelet Inhibition by Adjunctive Cilostazol Versus High Maintenance-Dose Clopidogrel In Patients with Acute Myocardial Infarction According to Cytochrome P450 2C19 Genotype

The aim of this study was to assess the degree of platelet inhibition by adjunctive cilostazol in patients with acute myocardial infarction (AMI) according to CYP2C19 genotype.

Although adjunctive cilostazol intensifies platelet inhibition in AMI patients, it is not established whether this regimen can overcome the loss-of-function effect of CYP2C19 variants.

We randomly assigned 126 AMI patients with available CYP2C19 genotyping to receive adjunctive cilostazol (triple group; n = 64) or high maintenance-dose (MD) clopidogrel of 150-mg/day (high-MD group; n = 62). Using conventional aggregometry and VerifyNow, platelet reactivity was measured at pre-discharge and 30-day follow-up. Primary endpoint was change in maximal platelet aggregation (Agg_max). High post-treatment platelet reactivity (HPPR) was defined as 5 μmol/l ADP-induced Agg_max > 50%.

In non-carriers, the two groups did not differ with respect to changes in platelet measures, and could achieve fewer rates of HPPR at 30-day follow-up (< 5%). In carriers, changes in 5 and 20 μmol/l ADP-induced Agg_max were significantly higher in the triple (n = 39) versus high-MD group (n = 38) (21.8 ± 13.9% vs. 9.0 ± 13.3%, p < 0.001, and 24.2 ± 17.2% vs. 7.7 ± 15.5%, p < 0.001, respectively). Likewise, changes in late platelet aggregation and P2Y₁₂ reaction unit were consistently greater in the triple vs. high-MD group. Fewer patients in the triple group met the criteria of HPPR at 30-day follow-up compared with the high-MD group (2.6% vs. 21.1%, p = 0.014).

Among AMI patients with CYP2C19 variants, adjunctive cilostazol enhances platelet inhibition and reduces the rate of HPPR, as compared with high-MD clopidogrel. (Adjunctive Cilostazol Versus High-MD ClopidogrEL in Patients With Acute Myocardial Infarction According to CYP2C19 genotype [ACCEL-AMI-CYP2C19]; NCT00915733).

No relevant conflicts of interest to declare.