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J Am Coll Cardiol, 2009; 53:1101-1109, doi:10.1016/j.jacc.2008.12.025
© 2009 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Randomized Comparison of Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With High Post-Treatment Platelet Reactivity

Results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) Randomized Study

Young-Hoon Jeong, MD, PhD*, Seung-Whan Lee, MD, PhD{ddagger}, Bong-Ryong Choi, MD*, In-Suk Kim, MD, PhD{dagger}, Myung-Ki Seo, MD*, Choong Hwan Kwak, MD, PhD*, Jin-Yong Hwang, MD, PhD* and Seong-Wook Park, MD, PhD{ddagger},*

* Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
{dagger} Department of Laboratory Medicine, Gyeongsang National University Hospital, Jinju, Korea
{ddagger} Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Manuscript received August 11, 2008; revised manuscript received December 2, 2008, accepted December 8, 2008.

* Reprint requests and correspondence: Dr. Seong-Wook Park, Department of Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea (Email: swpark{at}amc.seoul.kr).

Objectives: The purpose of this study was to determine the impact of adjunctive cilostazol in patients with high post-treatment platelet reactivity (HPPR) undergoing coronary stenting.

Background: Although addition of cilostazol to dual antiplatelet therapy enhances adenosine diphosphate (ADP)-induced platelet inhibition, it is unknown whether adjunctive cilostazol can reduce HPPR.

Methods: Sixty patients with HPPR after a 300-mg loading dose of clopidogrel were enrolled. HPPR was defined as maximal platelet aggregation (Aggmax) >50% with 5 µmol/l ADP. Patients were randomly assigned to receive either adjunctive cilostazol (triple group; n = 30) or high maintenance dose (MD) clopidogrel (high-MD group; n = 30). Platelet function was assessed at baseline and after 30 days with conventional aggregometry and the VerifyNow assay.

Results: Baseline platelet function measurements were similar in both groups. After 30 days, significantly fewer patients in the triple versus high-MD group had HPPR (3.3% vs. 26.7%, p = 0.012). Percent inhibitions of 5 µmol/l ADP-induced Aggmax and late platelet aggregation (Agglate) were significantly greater in the triple versus high-MD group (51.1 ± 22.5% vs. 28.0 ± 18.5%, p < 0.001, and 70.9 ± 27.3% vs. 45.3 ± 23.4%, p < 0.001, respectively). Percent inhibitions of 20 µmol/l ADP-induced Aggmax and Agglate were consistently greater in the triple versus high-MD group. Percent change of P2Y12 reaction units demonstrated a higher antiplatelet effect in the triple versus high-MD group (39.6 ± 24.1% vs. 23.1 ± 29.9%, p = 0.022).

Conclusions: Adjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day.

Key Words: platelet • high post-treatment platelet reactivity • adjunctive cilostazol • high maintenance dose clopidogrel

Abbreviations and Acronyms
  ACS = acute coronary syndrome
  ADP = adenosine diphosphate
  Agglate = late platelet aggregation at 5 min
  Aggmax = maximal platelet aggregation
  cAMP = cyclic adenosine monophosphate
  HPPR = high post-treatment platelet reactivity
  IPA = inhibition of platelet aggregation
  LD = loading dose
  LTA = light transmittance aggregometry
  MD = maintenance dose
  PCI = percutaneous coronary intervention
  PPP = platelet-poor plasma
  PRP = platelet-rich plasma
  PRU = P2Y12 reaction unit


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