Pharmacodynamic effect of cilostazol plus standard clopidogrel versus double-dose clopidogrel in patients with type 2 diabetes undergoing percutaneous coronary intervention.

Abstract

To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (CYP2C19*2/*3, CYP3A5*3)and ATP-binding cassette subfamily B1(ABCB1 C3435T) genetic polymorphisms in type 2 diabetes (T2DM) patients. T2DM patients were treated with TRIPLE (n = 41) or DOUBLE (n = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA(20)) between baseline and switching values. TRIPLE versus DOUBLE showed greater ΔMPA(20) (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2-16.3]; P < 0.001). Carriage of one (β coefficient, -5.4%; P = 0.162) and two CYP2C19 loss-of-function allele(s) (-8.3%; P = 0.007) were associated with lower ΔMPA(20) in DOUBLE-treated patients, but not in TRIPLE-treated patients. Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.