TABLE 2.

Definitions of established cardiovascular disease

Trial	Definition
ELIXA 9	Acute coronary syndrome defined as ST‐segment elevation MI (STEMI), non‐STEMI or unstable angina.
LEADER 10	≥1 of the following criteria: Prior MI Prior stroke or TIA Prior coronary, carotid or peripheral arterial revascularization >50% stenosis of coronary, carotid or lower extremity arteries History of symptomatic CHD documented by positive exercise stress test or any cardiac imaging or unstable angina with ECG changes Asymptomatic cardiac ischaemia documented by positive nuclear imaging test, exercise test or dobutamine stress echo Chronic heart failure NYHA class II‐III Chronic renal failure (eGFR < 60 mL/min per 1.73m2)
SUSTAIN‐6 11	≥1 of the following criteria: Prior MI Prior stroke or TIA Prior coronary, carotid or peripheral arterial revascularization >50% stenosis of coronary, carotid or lower extremity arteries History of symptomatic CHD documented by positive exercise stress test or any cardiac imaging or unstable angina with ECG changes Asymptomatic cardiac ischaemia documented by positive nuclear imaging test, exercise test, stress echo or any cardiac imaging Chronic heart failure NYHA class II‐III Chronic renal impairment (eGFR < 60 mL/min/1.73m2)
EXSCEL 12	≥1 of the following criteria: History of a major clinical manifestation of CAD, i.e. MI, surgical or percutaneous (balloon and/or stent) coronary revascularization procedure or coronary angiography showing ≥50% stenosis in a major epicardial artery or branch vessel Ischaemic cerebrovascular disease, including: History of ischaemic stroke. Strokes not known to be haemorrhagic will be allowed as part of this criterion History of CAD as documented by ≥50% stenosis documented by carotid ultrasound, MRI or angiography, with or without symptoms of neuro deficit Atherosclerotic PAD, as documented by objective evidence such as amputation because of vascular disease, current symptoms of intermittent claudication confirmed by an ankle‐brachial pressure index or toe brachial pressure index less than 0.9, or history of surgical or percutaneous revascularization procedure
Harmony 13	≥1 of the following criteria: CAD with either of the following: Documented history of spontaneous MI, at least 30 days before screening Documented CAD ≥ 50% stenosis in 1 or more major epicardial coronary arteries, determined by invasive angiography, or a history of surgical or percutaneous (balloon and/or stent) coronary revascularization procedure (at least 30 days before screening for percutaneous procedures and at least 5 years before screening for CABG) Cerebrovascular disease—any of the following: Documented history of ischaemic stroke, at least 90 days before study entry Carotid arterial disease with ≥50% stenosis documented by carotid ultrasound, magnetic resonance imaging or angiography, with or without symptoms of neuro deficit Carotid vascular procedure (e.g. stenting or surgical revascularization), at least 30 days before screening PAD with either of the following: Intermittent claudication and ankle‐brachial index < 0.9 in at least 1 ankle Prior non‐traumatic amputation or peripheral vascular procedure (e.g. stenting or surgical revascularization) because of peripheral arterial ischaemia
REWIND 14 , 33	≥1 of the following criteria: Prior MI Myocardial ischaemia by a stress test or with cardiac imaging Prior ischaemic stroke Coronary, carotid or peripheral revascularization Unstable angina Hospitalization for unstable angina with ECG changes, myocardial ischaemia on imaging, or need for percutaneous coronary intervention
PIONEER 6 15	≥1 of the following criteria: Prior MI Prior stroke or TIA Prior coronary, carotid or peripheral arterial revascularization >50% stenosis of coronary, carotid or lower extremity arteries History of symptomatic CHD documented by positive exercise stress test or any cardiac imaging or unstable angina with ECG changes Asymptomatic cardiac ischaemia documented by positive nuclear imaging test, exercise test, stress echo or any cardiac imaging Chronic heart failure NYHA class II‐III Moderate renal impairment (30‐59 mL/min per 1.73m2)

Abbreviations: ALT, alanine aminotransferase; BMI, body mass index; CABG, coronary artery bypass graphing; CAD, coronary artery disease; CHD, coronary heart disease; CKD, chronic kidney disease; CV, cardiovascular; DPP‐4, dipeptidyl peptidase‐4; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; ESKD, end‐stage kidney disease; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; HDL, high density lipid; IBD, irritable bowel disease; LDL, low density lipoprotein; LV, left ventricular; MACE, major adverse cardiac events; MEN2, multiple endocrine neoplasia type 2; MI, myocardial infarction; MRI, magnetic resonance imaging; MTC, medullary thyroid cancer; NYHA, New York Heart Association; OAM, oral antidiabetes medication; PAD, peripheral arterial disease; TIA, transient ischaemic attack.