Evaluating the Effect of Intracoronary N-Acetylcysteine on Platelet Activation Markers After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction Azadeh Eshraghi, PharmD, 1 Azita Hajhossein Talasaz, PharmD, 2,3 * Jamshid Salamzadeh, PharmD, 4 Mojtaba Salarifar, MD, 5 Hamidreza Pourhosseini, MD, 5 Yones Nozari, MD, 5 Mostafa Bahremand, MD, 6 Arash Jalali, PhD, 7 and Mohammad Ali Boroumand, MD 8 During percutaneous coronary intervention (PCI), trauma occurs in the arterial endothelium, resulting in platelet activation and aggregation. As platelet aggregation may lead to coronary thrombosis, antiplatelet agents are essential adjunctive therapies in patients undergoing PCI. The aim of this study was to determine the effect of the intracoronary administration of high-dose N-acetylcysteine (NAC) for the evaluation of its antiplatelet effects in human subjects. In this triple-blind trial, 147 patients undergoing primary PCI were enrolled. Finally, 100 patients were randomized to receive high-dose intracoronary NAC (100 mg/kg bolus, followed by 10 mg$kg 21 $h 21 intracoronary continued intrave- nously for 12 hours) (n 5 50) or dextrose solution (n 5 50). Platelet activation biomarkers were measured before and 24 hours after the procedure. Secondary end points, comprising all-cause death, reinfarction, and target-vessel revascularization, were assessed at 30 days and 2 years. In comparison with the placebo, NAC could not reduce the level of platelet activation biomarkers within a 24-hour period after its prescription. Major adverse clinical events at 30 days and 2 years were infrequent and not statistically different between the 2 groups. Our results revealed that NAC, compared with the placebo, did not provide an additional clinical benefit as an effective antiplatelet agent after PCI. Keywords: NAC, platelet activation, primary percutaneous coronary intervention, reperfusion ischemia INTRODUCTION Coronary artery disease is one of the main causes of morbidity and mortality in the modern world. 1 Percu- taneous coronary intervention (PCI) remains an effec- tive treatment for coronary artery disease. 2 However, restenosis, defined as the renarrowing of the vessel lumen, may occur as an adverse reaction in patients 3 mainly within 6 months after PCI. 4 The exact mecha- nisms of restenosis have not been fully understood, but they include inflammation, proliferation, and matrix remodeling, which are followed by platelet, leukocyte, and coagulation system activation. 5 Platelet response to vascular injury begins immediately after PCI. Fibrin and platelet–rich thrombus formation 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy- International Campus, Iran University of Medical Sciences, Tehran, Iran; 2 Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 3 Department of Pharmaceutical Care, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; 4 Department of Clinical Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5 Cardiology Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; 6 Cardiology Department, Kermanshah University of Medical Scien- ces, Kermanshah, Iran; 7 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; and 8 Depart- ment of Molecular Pathology, Tehran Heart Center, Tehran, Iran. The authors have no conflicts of interest to declare. *Address for correspondence: Assistant Professor of Clinical Phar- macy, Tehran Heart Center, Tehran University of Medical Scien- ces, Tehran, Iran 1411713138. E-mail: a-talasaz@tums.ac.ir American Journal of Therapeutics 0, 1–8 (2015) 1075–2765 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.americantherapeutics.com Copyright Ó 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.