Although both enteric-coated and plain formulations of aspirin are being used commonly, there are no high-quality comparisons between these formulations with respect to clinical efficacy outcomes in patients with atherosclerotic cardiovascular diseases (ASCVD). Air pollution is also a major contributor to the excess risk of cardiovascular events in many regions of the world. However, little is known about the effect of individual-level mitigation strategies against air pollution in reducing cardiovascular outcomes. The purpose of the first randomization is to compare the efficacy and safety of enteric-coated versus plain low-dose (81 mg) aspirin formulations in a double-blind fashion. The second randomization compares a multifaceted intervention including one-page educational flashcard, cell phone text messages alerting participants on polluted days, recommending them to stay indoors or wear KN-95 facemasks provided by the study team in case of necessary outdoor activity, and recommendation to consume citrus fruits on polluted days versus usual care. Both randomization are powered for clinical outcomes and the results will inform practice.
Previous or recent documented type I myocardial infarction *(if not specified, will be assumed as type I)
History of coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery)
History of obstructive CAD (>50% stenosis) documented by coronary computed tomography (CT) or conventional angiography
Previous or recent acute ischemic limb event (>7 days prior)
Being within 72 days of acute/unstable atherosclerotic cardiovascular events (acute myocardial infarction, acute limb event, and acute ischemic stroke), or within 72 hours of revascularization.
Patients receiving triple antithrombotic therapy
History of upper gastrointestinal bleeding within the past 30 days
History of intracranial hemorrhage within the past 30 days
Factorial
Enteric-coated aspirin
DrugEnteric-coated aspirin tablet 81 mg, once daily
Plain aspirin
DrugPlain aspirin tablet 81 mg, once daily
Hybrid strategy
Other interventionA hybrid strategy composed from: * A one-page educational flashcard * Alerting patients on highly polluted days via text message * Encouraging patients to stay at home or minimizing outdoor activity on highly polluted days * Encouraging patients via text message to wear KN-95 facemasks (provided by the investigators of this study) during outdoors time on highly polluted days * Encouraging patients to consume citrus fruits during highly polluted days
Composite of fatal or nonfatal ischemic stroke (not deemed to be related to systemic hypotension), type I myocardial infarction, and acute limb events
Time to the first occurrence of an outcome composed of any endpoint that fulfills the definite criteria for diagnosis of at least one of the ischemic stroke, type I myocardial infarction, or acute limb event (whether leading to the patient's death or not) as defined in the description of the related secondary outcomes This outcome is assigned as the primary efficacy outcome for the first randomization.
Composite of non-fatal ischemic stroke (not deemed to be related to systolic hypotension), type I myocardial infarction, acute limb events, or cardiovascular death
Time to the first occurrence of an outcome composed of any endpoint that fulfills the definite criteria for diagnosis of at least one of the ischemic stroke, type I myocardial infarction, or acute limb event, and don not result in patient death as defined in the description of the related secondary outcomes This outcome is assigned as the primary outcome for the second randomization.
Type I myocardial infarction
Time to the first occurrence of type I myocardial infarction. Type I myocardial infarction is defined as spontaneous clinical syndrome related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection, with resulting intraluminal thrombus and leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis. This classification requires the detection of a rise and/or fall of cardiac biomarker values (preferably cTn) with at least 1 value \>99th percentile of the URL and at least 1 of the following: 1- Symptoms of myocardial ischemia 2- New or presumed new significant ST-segment T wave changes or new left bundle branch block on the ECG 3- Development of pathological Q waves on the ECG 4- Imaging evidence of new loss of myocardium or new regional wall motion abnormality 5- Identification of an intracoronary thrombus by angiography or autopsy
Ischemic stroke (not deemed to be related to systemic hypotension)
Time to the first occurrence of ischemic stroke. Ischemic stroke is defined as an episode of acute neurological dysfunction caused by focal cerebral, spinal, or retinal infarction as a result of arterial thrombosis and/or thromboembolism (not deemed to be related to systemic hypotension/hypoperfusion), and lasting ≥ 24 hours or to time of death with residual neurological sequelae
Acute limb event
A limb-threatening ischemia that is confirmed by limb hemodynamics or imaging and leads to an acute vascular intervention (i.e., pharmacologic \[heparin, thrombolysis\], peripheral arterial surgery/reconstruction, peripheral angioplasty/stenting, and/or limb amputation) within 30 days of onset of symptoms. In case of lack of confirmation by limb hemodynamics or imaging, the absence of pedal pulses is acceptable as the hemodynamic criterion for acute limb ischemia
All-cause death
Death due to any causes (cardiovascular, non-cardiovascular, or undetermined) within the follow-up period
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Rajaie Cardiovascular Medical and Research Center
Lead sponsor
Brigham and Women's Hospital
Collaborator
