Effect of cilostazol addition or clopidogrel doubling on platelet function profiles in diabetic patients undergoing a percutaneous coronary intervention.

Background: We investigated the pharmacodynamic effect of cilostazol addition (100 mg twice, Triple) or clopidogrel doubling (150 mg daily, Double) on standard dual antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients with clopidogrel resistance undergoing a percutaneous coronary intervention.

Methods And Results: This was a prospective, randomized, cross-over platelet function study. Percent inhibition less than 20% was used as the cutoff value of clopidogrel resistance. After percutaneous coronary intervention, a total of 50 T2DM patients with clopidogrel resistance were assigned to receive cilostazol 100 mg twice daily or clopidogrel 150 mg daily for 28 days; afterwards, they received cross-over treatment for another 28 days. Eight patients were excluded because of side effects and follow-up loss. The platelet function test using VerifyNow was performed at three time points: at baseline (T0), 28 days after randomization (T1), and 28 days after cross-over treatment (T2).A total of 42 T2DM patients completed the study protocol. The clopidogrel resistance improved significantly following cilostazol addition or clopidogrel doubling treatment compared with baseline (52.9±27.0 in Triple, 45.4±16.8% in Double, P<0.001 in both). This effect continued after cross-over treatment (58.1±26.1 and 41.0±20.0%, respectively, both P<0.05). A head-to-head comparison between two groups showed a lower P2Y12 reaction unit (PRU) and higher percentage of platelet inhibition in the Triple than those in the Double group (PRU, 138.7±88.2 vs. 198.8±19.5, P=0.049; %platelet inhibition, 58.1±26.1 vs. 40.97±20.0, P=0.048).

Conclusion: Adjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy might be a more effective strategy for overcoming clopidogrel resistance than clopidogrel doubling treatment.