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

Diabetes Care. 2012 Nov;35(11):2194-7. doi: 10.2337/dc11-2351. Epub 2012 Jul 26.

Abstract

Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.

Trial registration: ClinicalTrials.gov NCT00915733 NCT01012193.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cilostazol
  • Clopidogrel
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Humans
  • Male
  • Percutaneous Coronary Intervention / methods*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic / genetics
  • Tetrazoles / administration & dosage*
  • Tetrazoles / therapeutic use*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Tetrazoles
  • Clopidogrel
  • Cilostazol
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00915733
  • ClinicalTrials.gov/NCT01012193