ACCEL-LOADING-ACS Study

ACCELerated Inhibition of Platelet Aggregation, Inflammation and Ischemia-reperfusion Injury by Adjunctive Cilostazol Loading in Patients With Acute Coronary Syndrome

The purpose of this study is to determine whether adjunctive cilostazol loading/maintenance to standard treatment (aspirin, clopidogrel, and statin) is effective in reduction of major adverse cardiovascular events, platelet activation, inflammation and myonecrosis in patients with non-ST-elevation acute coronary syndrome (ACS)undergoing percutaneous coronary intervention (PCI).

In ACS patients, platelet activation, inflammation, and ischemia-reperfusion injury can be closely associated with the risk of post-PCI myonecrosis and ischemic events occurrence. In the ACCEL-AMI (Adjunctive Cilostazol versus high maintenance-dose ClopidogrEL in patients with Acute Myocardial Infarction)study, adjunctive cilostazol increased platelet inhibition compared with double-dose clopidogrel. Meanwhile, statins can reduce the extent of myonecrosis via limiting inflammation and myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. In animal study, the combination of low-dose statin with cilostazol synergistically limits infarct size. Multiple studies have shown that cilostazol can influence inflammation and RISK pathway using the similar pathway with statin. This study will be performed to evaluate the role of adjunctive cilostazol in platelet inhibition, inflammation, and myonecrosis compared with standard treatment.

Loading: aspirin 300mg + clopidogrel 600mg Maintenance: aspirin 200mg/d + clopidogrel 75mg/d for 1 month

Loading: cilostazol 200mg + aspirin 300mg + clopidogrel 600mg Maintenance: cilostazol 100mg bid+ aspirin 200mg/d+ clopidogrel 75mg/d for 1 month

24hr post-procedural variations from baseline of inflammation markers (IL-6, TNF-alpha, cell adhesion molecules (VCAM, ICAM, E-selectin)

Inclusion Criteria: at least 18 years of age Non-ST-elevation ACS patients undergoing PCI within 48 hours after hospitalization Exclusion Criteria: ST segment elevation acute myocardial infarction NSTE ACS with high-risk features warranting emergency coronary angiography Oral anticoagulation therapy with warfarin Use of pre-procedural glycoprotein IIb/IIIa inhibitor Contraindication to antiplatelet therapy AST or ALT ≥ 3 times upper normal Left ventricular ejection fraction < 30% WBC < 3,000/mm3, platelet < 100,000/mm3 Creatinine ≥ 3 mg/dl stroke within 3 months

Patti G, Pasceri V, Colonna G, Miglionico M, Fischetti D, Sardella G, Montinaro A, Di Sciascio G. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007 Mar 27;49(12):1272-8. doi: 10.1016/j.jacc.2007.02.025.

Jeong YH, Hwang JY, Kim IS, Park Y, Hwang SJ, Lee SW, Kwak CH, Park SW. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: Results of the adjunctive cilostazol versus high maintenance dose clopidogrel in patients with AMI (ACCEL-AMI) study. Circ Cardiovasc Interv. 2010 Feb 1;3(1):17-26. doi: 10.1161/CIRCINTERVENTIONS.109.880179. Epub 2010 Jan 26.