Table 1 Characteristics of included studies
Study | Study design | Study population | Inclusion criteria | Exclusion criteria | Median follow-up | Primary endpoint | Aspirin treatment regimen | N | Placebo-controlled |
|---|---|---|---|---|---|---|---|---|---|
Peto et al. [28] (British Doctors’ Study) | Open-label RCT | Male British doctors | Male doctors residing in the UK and listed in the 1977 Medical Directory who previously replied to a questionnaire about their smoking habits | -Ongoing aspirin use -History of peptic ulcer, strike or myocardial infarction | 6 years | Myocardial infarction, stroke, transient ischemic attacks | 500 mg once daily | 5139 | No |
Steering Committee of the Physicians’ Health Study Research Group [30] US Physicians’ Health Study 1989 (PHS) | Double-blind RCT | Healthy male doctors | -Male physician -40 to 84 years of age | -History of myocardial infarction, stroke, transient ischemic attack, cancer (except nonmelanoma skin cancer) -Current liver or kidney disease -Peptic ulcer -Gout -Contraindications to aspirin consumption -Current use of aspirin, other platelet-active drugs, nonsteroidal anti-inflammatory drugs, or current use of vitamin A supplement | 5 years | Myocardial infarction, stroke, cardiovascular mortality | 325 mg on alternate days | 22,071 | Yes |
The Medical Research Council’s General Practice Research Framework [25] Thrombosis Prevention Trial 1998 (TPT) | Double-blind RCT | Men at high risk of IHD | -Males between age 46 and 69 -Top 20% of risk score distribution -Top 25% in regions with particularly high ischemic heart disease (IHD) mortality rates | -Peptic ulceration -History of possible or definite myocardial infarction or stroke -Medication not compatible with trial treatment | 6.8 years | All IHD (sum of coronary death and fatal and nonfatal myocardial infarction) | 75 mg once daily | 5085 | Yes |
Hansson et al. [27] (Hypertension Optimal Treatment Trial, HOT) | Double-blind RCT | Men and women with hypertension | -Age 50 to 80 years -Hypertension -Diastolic blood pressure between 100 and 115 mmHg | -Suspicion of incorrect inclusion or data handling | 3.8 years | MACE was defined as all (fatal and nonfatal) myocardial infarctions and strokes and all other cardiovascular deaths | 75 mg once daily | 18,790 | Yes |
Collaborative Group of the Primary Prevention Project [26] Primary Prevention Project (PPP) 2001 | Open-label RCT | Men and women with one or more risk factors for coronary heart disease (CHD) | -Age > 65 years -Hypertension (SBP ≥ 160, DBP ≥ 95) -Hypercholesterolemia -Diabetes mellitus -Obesity -Family history of myocardial infarction before 55 years of age in at least one parent or sibling | -Treatment with antiplatelet drugs, chronic -Chronic use of anti-inflammatory drugs or anticoagulants -Contraindications to aspirin -Disease with predictable poor short-term prognosis -Predictable psychological or logistical difficulties affecting compliance with the trial requirements | 3.6 years | Cumulative rate of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke | 100 mg once daily | 4495 | No (vitamin E) |
Ridker et al. [29] (Women’s Health Study, WHS) | Double-blind RCT | Females aged 45 and over | -Women aged ≥ 45 | -No history of coronary heart disease, cerebrovascular disease, cancer (except nonmelanoma skin cancer), other major chronic illnesses -History of side-effects to any of the study medications -Intake of aspirin or nonsteroidal anti-inflammatory drugs more than once a week -Use of anticoagulants or corticosteroids -Intake of supplements of vitamins A and E and beta-carotene more than once a week | 10.1 years | Nonfatal myocardial infarction, nonfatal stroke, or death from any cardiovascular causes | 100 mg on alternate days | 39,876 | Yes |
Belch et al. [37] (POPADAD trial) | Double-blind RCT | Diabetic patients aged 40 and over with a reduced ABI | -Men and women aged ≥ 40 -Diagnosis of type I or II diabetes mellitus -Asymptomatic peripheral artery disease (ABI ≤ 0.99) | -Evidence of symptomatic cardiovascular disease -Use of aspirin or antioxidant therapy -Peptic ulceration, severe dyspepsia -Bleeding disorder -Intolerance to aspirin -Suspected serious physical illness with reduced life expectancy -Congenital heart disease -Psychiatric illness | 6.7 years | Two hierarchical composite primary endpoints: (1) death from coronary heart disease or stroke, nonfatal myocardial infarction or stroke, or above ankle amputation for critical limb ischemia and (2) death from coronary heart disease or stroke | 100 mg once daily | 1276 | Yes |
Ogawa et al. [38] (Saito et al. [36], 10-year follow-up) (JPAD trial) | Open-label RCT | Patients with diabetes | -Age between 30 and 85 years -Type 2 diabetes mellitus -Ability to give informed consent | -Ischemic ECG abnormalities -History of CHD -History of coronary angiography -History of cerebrovascular disease -History of arteriosclerotic disease requiring treatment -Atrial fibrillation -Pregnancy -Use of antiplatelet/antithrombotic therapy -History of severe gastric or duodenal ulcer -Severe renal or liver dysfunction -Allergy to aspirin | 4.4 years/10.3 years | Any atherosclerotic event, which was a composite of sudden death, death from coronary, cerebrovascular or aortic causes, nonfatal acute myocardial infarction, unstable angina, newly developed exertional angina, nonfatal ischemic and hemorrhagic stroke, transient ischemic attack, nonfatal aortic or disease | 81–100 mg once daily | 2539 | No |
Fowkes et al. [34] (Aspirin for Asymptomatic Atherosclerosis trial, AAA) | Double-blind RCT | Men and women with a low ABI | -Men and women aged 50 to 75 years -No history of vascular disease -ABI ≤ 0.95 | -History of myocardial infarction, stroke, angina, or peripheral artery disease -Use of antiplatelet/antithrombotic therapy -Severe renal or liver dysfunction -Severe indigestion -Receiving chemotherapy -High/low hematocrit -Contraindication to aspirin | 8.2 years | Composite of initial fatal or nonfatal coronary event or stroke or revascularization | 100 mg once daily | 3350 | Yes |
Ikeda et al. [35] (Japanese Primary Prevention Trial, JPPP) | Open-label RCT | Men and women with one or more risk factors for CHD | -Men and women aged 60 to 85 years -No atherosclerotic disease -Hypertension (SBP ≥ 140, DBP ≥ 90) -Dyslipidemia -Diabetes mellitus | -History of coronary artery disease -History of cerebrovascular disease -Atherosclerotic disease requiring surgery -Atrial fibrillation -Peptic ulcer or conditions associated with bleeding -Aspirin-sensitive asthma and history of aspirin allergy -Receiving antiplatelet agents, anticoagulants, or nonsteroidal anti-inflammatory drugs | 5 years | Composite of death from cardiovascular causes (myocardial infarction, stroke, and other cardiovascular causes), nonfatal stroke, and nonfatal myocardial infarction | 100 mg once daily | 14,464 | No |
Gaziano et al. [17] (ARRIVE trial) | Double-blind RCT | Men and women with multiple risk factors for CHD | -Males aged 55 years and older with between 2 and 4 risk factors -Females aged 60 years and older with between 3 and 4 risk factors -Risk factors were high cholesterol or LDL -Current smoking -Low HDL cholesterol -High blood pressure -Receiving medication for high blood pressure -Positive family history of cardiovascular heart disease | -Diabetes mellitus -History of a vascular event, such as stroke, myocardial infarction, coronary artery angioplasty, or stenting -Coronary artery bypass graft -Relevant arrhythmias -Congestive heart failure -Vascular intervention -Ongoing antiplatelet therapy -High risk of gastrointestinal and other bleeding, including those with a history of gastric or duodenal ulcers or gastrointestinal bleeding -Requiring concomitant use of anticoagulants or frequent use of nonsteroidal anti-inflammatory drugs | 5 years | Composite outcome of confirmed myocardial infarction, stroke, cardiovascular death, unstable angina, or transient ischemic attack | 100 mg once daily | 12,546 | Yes |
The ASCEND Study Collaborative Group [18] (ASCEND trial) 2018 | Single-blind RCT | Diabetic men and women aged ≥ 40 | -Men and women with at least 40 years of age -Diagnosis of diabetes mellitus -No known cardiovascular disease | -Clear indication for aspirin -Contraindication to aspirin -Presence of other clinically significant conditions that might limit adherence to the trial regimen for at least 5 years | 7.4 years | First serious vascular event, which was defined as a composite of nonfatal myocardial infarction, nonfatal stroke (excluding confirmed intracranial hemorrhage) or transient ischemic attack, or death from any vascular cause (excluding confirmed intracranial hemorrhage) | 100 mg once daily | 15,480 | Yes |
McNeil et al. [19] (ASPREE trial) | Double-blind RCT | Elderly men and women | -Men and women aged ≥ 70 (≥ 65 in Hispanics and Latinos) -Free from overt coronary heart disease, overt cerebrovascular disease, atrial fibrillation, a clinical diagnosis of dementia, clinically significant physical disability, a high risk of bleeding, anemia, and a known contraindication to or inability to take aspirin | -Current regular use of an anticoagulant or antiplatelet medication other than aspirin -Systolic blood pressure of 180 mmHg or more or a diastolic blood pressure of 105 mmHg or more -A medical indication for or contraindication to regular aspirin therapy -Presence of a condition that, in the opinion of the primary care physician, was likely to result in death within 5 years | 4.7 years | Prespecified secondary endpoint was cardiovascular disease, being a composite of fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure | 100 mg once daily | 19,114 | Yes |