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

Although enteric-coated aspirin is widely used instead of chewable formulations in patients with atherosclerotic cardiovascular disease (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.

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 2 × 2 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 h of acute/unstable ASCVD or revascularization, triple antithrombotic therapy, active/recent bleeding, life expectancy <1 year, or other barriers or unwillingness for enrolment. Eligible consenting patients are randomized, in a double-blind fashion, to enteric-coated vs. chewable aspirin 81 mg daily and (via factorial randomization) to a hybrid strategy to mitigate the adverse effects of air pollution vs. usual care. The hybrid strategy includes (i) an educational flashcard, (ii) real-time air quality alerts via cellular text messages, and (iii) recommendations to (a) limit outdoor activity or (b) use a KN-95 facemask when outdoors, or (c) increase citrus fruit intake on days with elevated pollution levels. The primary efficacy outcome for the aspirin randomization is a composite of fatal/non-fatal ischaemic stroke, thrombotic/thromboembolic myocardial infarction, and acute limb ischaemia. 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. Enrolment was completed on 28 January 2026. Clinical follow-up and blinded event adjudications are ongoing.

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.