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.

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.