Pharmacodynamic Effect of Cilostazol Plus Standard Clopidogrel Versus Double-Dose Clopidogrel in Patients With Type 2 Diabetes Undergoing Percutaneous Coronary Intervention

Abstract

OBJECTIVETo 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.RESEARCH DESIGN AND METHODST2DM 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 (ΔMPA20) between baseline and switching values.RESULTSTRIPLE versus DOUBLE showed greater ΔMPA20 (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 ΔMPA20 in DOUBLE–treated patients, but not in TRIPLE-treated patients.CONCLUSIONSAmong T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.