Coated or chewable aspirin and a hybrid air pollution mitigation strategy in patients with atherosclerotic disease: rationale and design of the COATED-AIR randomized trial
Year: 2026
Type: article
Study design: Study Protocol
Abstract: BACKGROUND: Although enteric-coated aspirin is widely used instead of chewable formulations in patients with atherosclerotic cardiovascular diseases (ASCVD), its effects on cardiovascular and gastrointestinal outcomes remain uncertain. Separately, air pollution is a driver of cardiovascular risk, yet individual-level interventions have not been tested in outcomes trials. METHODS AND RESULTS: The Coated Or Chewable Aspirin in Patients with Established AThErosclerotic Disease and a Hybrid Strategy to Mitigate the Adverse Effects of AIR Pollution (COATED-AIR) is a randomized trial with a 2x2 factorial design planned to address these knowledge gaps. Patients with ASCVD receiving low-dose aspirin are considered for inclusion. Major exclusion criteria consist of being within 72 hours of acute/unstable ASCVD or revascularization, triple antithrombotic therapy, active/recent bleeding, life expectancy <1 year, or other barriers or unwillingness for enrollment. Eligible consenting patients are randomized, in a double-blind fashion, to enteric coated vs chewable aspirin 81mg daily, and (via factorial randomization) to a hybrid strategy to mitigate the adverse effects of air pollution vs usual care. The hybrid strategy includes 1. an educational flashcard, 2. real-time air quality alerts via cellular text messages, and recommendations to 2a. limit outdoor activity or 2b. to use a KN-95 facemask when outdoors, and 2c. to increase citrus fruit intake on days with elevated pollution levels. The primary efficacy outcome for the aspirin randomization is a composite of fatal/nonfatal ischemic stroke, thrombotic/thromboembolic myocardial infarction, and acute limb ischemia. For the AIR randomization, other forms of cardiovascular death are additionally included in the primary composite outcome. The median planned duration of follow-up is 2 years. Enrollment was completed on 01/28/2026. Clinical follow-up and blinded event adjudications are ongoing. CONCLUSION: COATED-AIR will determine whether aspirin coating affects its safety or effectiveness, and whether individual-level strategies can mitigate cardiovascular risks from air pollution in patients with ASCVD.
Authors: Behnood Bikdeli, Azita H Talasaz, Hooman Bakhshandeh, Mohammad Sadegh Hassanvand, Hessam Kakavand, Sepehr Jamalkhani, Sina Rashedi, Sara Tayyebi, Mohammadreza Babaei, Erfan Kohansal, Hamed Ghoshouni, Yasmin Mohtasham Kia, Mahsa Nikkhoo, Bahram Mohebbi, Maryam Aghakouchakzadeh, Saeed Alipour-Parsa, Armin Elahifar, Ehsan Khalilipur, Razieh Omidvar, Maryam Mehrpooya, Seyed Hashem Sezavar, David Jimenez, Luis Jara Palomares, Saeideh Mazloomzadeh, Naser Hadavand, Mehdi Ansari Dogaheh, Majid Maleki, Feridoun Noohi, Luis Ortega-Paz, Jayant K Raikhelkar, Philippe Gabriel Steg, Renato D Lopes, Raffaele De Caterina, Mehdi H Shishehbor, Loren Laine, Dominick J Angiolillo, Sanjay Rajagopalan, Ajay J Kirtane, Gregory Piazza, Gregory Y H Lip, Roxana Mehran, Harlan M Krumholz, Paul M Ridker, Parham Sadeghipour
Institutions: Brigham and Women's Hospital, Yale New Haven Hospital, Harvard University, Yale University, Mass General Brigham, NewYork–Presbyterian Hospital, Virginia Commonwealth University, Columbia University Irving Medical Center, Shaheed Rajaei Cardiovascular Medical and Research Center, Center for Air Pollution Research, Institute for Environmental Research, Tehran University of Medical Sciences, Iran University of Medical Sciences, Shahid Beheshti University, Shahid Beheshti University of Medical Sciences, Cardiovascular Diseases Research Institute, Imam Khomeini Hospital, Universidad de Alcalá, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Kerman University of Medical Sciences, University of Florida, University of Florida Health Science Center, Herbert Irving Comprehensive Cancer Center, Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Laboratoire de Recherche Vasculaire Translationnelle, Hôpital Bichat-Claude-Bernard, Duke University, University of Pisa, Azienda Ospedaliera Universitaria Pisana, University Hospitals of Cleveland, Case Western Reserve University, VA Connecticut Healthcare System, Medical University of Białystok, University of Liverpool, Aalborg University, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,501
OpenAlex ID: W7214072164