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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, Bong-Ryong Choi, MD^_*, In-Suk Kim, MD, PhD, Myung-Ki Seo, MD^_*, Choong Hwan Kwak, MD, PhD^_*, Jin-Yong Hwang, MD, PhD^_* and Seong-Wook Park, MD, PhD^,_*

^_* Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
Department of Laboratory Medicine, Gyeongsang National University Hospital, Jinju, Korea
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 (Agg_max) >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 Agg_max and late platelet aggregation (Agg_late) 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 Agg_max and Agg_late 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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