Table 2.

Summary of the key trials of aspirin in primary prevention

Study	Trial design	Treatment regimen	Primary endpoint(s)
British Doctors’ Study (BDS) [20]	Randomized, non-blinded; apparently healthy male doctors aged 19−90 years (N = 5,139); 47 % aged <60 years); mean follow-up 6 years	Aspirin 500 mg/day (ordinary, soluble, or effervescent as desired) or enteric-coated aspirin 300 mg/day or no aspirin	Reduction in incidence of, and mortality from, stroke, MI, or other vascular conditions
Physicians’ Health Study (PHS) [22]	Randomized, double-blind, placebo-controlled; healthy male physicians aged 40−84 years (N = 22,071); mean follow-up 5.2 years (terminated early)	Aspirin 325 mg every other day or no aspirin	Incidence of first MI (fatal, non-fatal, total), stroke (fatal, non-fatal, total), and combined events (non-fatal MI, non-fatal stroke, CV death)
Thrombosis Prevention Trial (TPT) [23]	Randomized, factorial, double-blind; men aged 45–69 years, at high risk of ischemic heart disease (N = 5,499); mean follow-up 6.8 years	Aspirin 75 mg/day and placebo warfarin, placebo aspirin and placebo warfarin, active aspirin and active warfarin, or placebo aspirin and active warfarin	All ischemic heart disease, defined as the sum of coronary death and fatal and non-fatal MI
Hypertension Optimal Treatment study (HOT) [18]	Randomized, double-blind; men and women with hypertension aged 50−80 years (N = 18,790); mean follow-up 3.8 years (range 3.3−4.9 years)	Aspirin 75 mg/day randomly added to antihypertensive treatment (felodipine and if necessary stepwise ACE inhibitors, beta-blockers, diuretics)	Incidence of CV complications
Primary Prevention Project (PPP) [16]	Randomized, open-label, factorial; patients (mean age 64.4 years) with one or more of the following: hypertension, hypercholesterolemia, diabetes, obesity, family history of premature MI, or individuals who are elderly (N = 4,495); mean follow-up 3.6 years (terminated early)	Aspirin 100 mg/day or no aspirin	Cumulative rate of CV death, non-fatal MI, and non-fatal stroke
Women’s Health Study (WHS) [21]	Randomized, double-blind, placebo-controlled, 2 × 2 factorial; apparently healthy women aged ≥45 years (N = 39,876); mean follow-up 10.1 years (range 8.2−10.9 years)	Aspirin 100 mg every other day or placebo	Combination of non-fatal MI, non-fatal stroke, CV-related death Incidence of total malignant neoplasms of epithelial cell origin
Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial (JPAD) [19]	Multicenter, prospective, randomized, open-label, blinded study in Japan; patients (N = 2,539) aged 30–85 years with type 2 diabetes without a history of atherosclerotic disease; median follow-up 4.37 years	Aspirin 81 or 100 mg daily or no aspirin	Atherosclerotic events, including fatal or non-fatal ischemic heart disease, fatal or non-fatal stroke, and peripheral arterial disease
Prevention of Progression of Arterial Disease and Diabetes trial (POPADAD) [15]	Multicenter, randomized, double-blind, 2 × 2 factorial, placebo-controlled; adults (N = 1,276) aged ≥40 years with type 1 or 2 diabetes and an ankle brachial pressure index ≤0.99 but no symptomatic CVD; median follow-up for randomized participants 6.7 years	Daily aspirin 100-mg tablet plus antioxidant capsule (n = 320), aspirin tablet plus placebo capsule (n = 318), placebo tablet plus antioxidant capsule (n = 320), or placebo tablet plus placebo capsule (n = 318)	Two hierarchical composite primary endpoints: death from CHD or stroke, non-fatal MI or stroke, or amputation above the ankle for critical limb ischemia; and death from CHD or stroke
Aspirin for Asymptomatic Atherosclerosis Trial (AAAT) [17]	Randomized, double-blind, controlled; men and women (N = 3,350) aged 50–75 years who were free from CVD and had a low ankle brachial pressure index (≤0.95); mean (SD) follow-up 8.2 (1.6) years	Daily aspirin 100-mg aspirin (enteric coated) or placebo	Composite of initial fatal or non-fatal coronary event or stroke or revascularization

ACE angiotensin-converting enzyme, CHD coronary heart disease, CV cardiovascular, CVD cardiovascular disease, MI myocardial infarction, SD standard deviation