Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial
Open accessAbstract
Background The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. Methods ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. Findings Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). Interpretation The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies. Funding Bayer.
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In ARRIVE, gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of individuals in the aspirin group vs 0.46% in the placebo group (HR 2.11; P = 0.0007).
“Gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of individuals in the aspirin group vs. 0.46% in the placebo group (HR 2.11 [95% ; P = 0.0007).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [180]
Two other large randomized trials of aspirin for primary prevention, ARRIVE (in people without diabetes) and ASPREE (in the elderly, 11% with diabetes), found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding.
“Two other large, randomized trials of aspirin for primary prevention, in people without diabetes (ARRIVE [Aspirin to Reduce Risk of Initial Vascular Events]) (180) and in the elderly (ASPREE [Aspirin in Reducing Events in the Elderly]) (181), in which 11% of participants had diabetes, found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [180]
In ARRIVE, the primary end point occurred in 4.29% vs 4.48% of individuals in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81-1.13]; P = 0.60).
“In ARRIVE, with 12,546 individuals over a period of 60 months of follow-up, the primary end point occurred in 4.29% vs. 4.48% of individuals in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81-1.13];P = 0.60).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [180]
Two other large randomized trials of aspirin for primary prevention, ARRIVE in people without diabetes and ASPREE in the elderly (11% with diabetes), found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding.
“Two other large, randomized trials of aspirin for primary prevention, in people without diabetes (ARRIVE [Aspirin to Reduce Risk of Initial Vascular Events]) (174) and in the elderly (ASPREE [Aspirin in Reducing Events in the Elderly]) (175), in which 11% of participants had diabetes, found no benefit of aspirin on the primary efficacy end point and an increased risk of bleeding.”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [174]
In ARRIVE, gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of individuals in the aspirin group vs 0.46% in the placebo group (HR 2.11 [95% CI 1.36-3.28]; P = 0.0007).
“Gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of individuals in the aspirin group vs. 0.46% in the placebo group (HR 2.11 [95% CI 1.36–3.28]; P = 0.0007).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [174]
In ARRIVE, the primary end point occurred in 4.29% vs 4.48% of individuals in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81-1.13]; P = 0.60).
“In ARRIVE, with 12,546 individuals over a period of 60 months of follow-up, the primary end point occurred in 4.29% vs. 4.48% of individuals in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81–1.13]; P = 0.60).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [174]
In ARRIVE, GI bleeding events occurred more with aspirin (0.97% vs 0.46%; HR 2.11, 95% CI 1.36-3.28; P=0.0007).
“Gastrointestinal bleeding events (characterized as mild) occurred in 0.97% of patients in the aspirin group vs. 0.46% in the placebo group (HR 2.11 [95% CI 1.36 -3.28]; P = 0.0007).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [145]
In ARRIVE, aspirin did not reduce the primary efficacy endpoint versus placebo (4.29% vs 4.48%; HR 0.96, 95% CI 0.81-1.13; P=0.60).
“In ARRIVE, with 12,546 patients over a period of 60 months follow-up, the primary end point occurred in 4.29% vs. 4.48% of patients in the aspirin versus placebo groups (HR 0.96 [95% CI 0.81 -1.13]; P = 0.60).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [145]
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- Authors
- Gaziano, J. M., Brotons, C., Coppolecchia, R., Cricelli, C., Darius, H., Gorelick, P. B., Howard, G., Pearson, T. A., Rothwell, P. M., Ruilope, L. M., Tendera, M., & Tognoni, G.
- Affiliations
- Brigham and Women's Hospital (US)
- Institut de Recerca Sant Pau (ES)
- Bayer (United States) (US)
- Società Italiana di Medicina Generale (IT)
- Vivantes Klinikum (DE)
- Mercy Health (US)
- University of Alabama at Birmingham (US)
- University of Florida (US)
- University of Oxford (GB)
- Universidad Complutense de Madrid (ES)
- Mario Negri Institute for Pharmacological Research (IT)
- Corresponding author
- Gaziano, J Michael
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 392
- Issue
- 10152
- Pages
- 1036-1046
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC7255888
- OpenAlex
- W2888108651
- Cited by
- 883
- References
- 16
- Citations by year
- 2026: 54 · 2025: 79 · 2024: 85 · 2023: 93 · 2022: 112 · 2021: 127 · 2020: 144 · 2019: 158 · 2018: 28 · 2017: 3
- FWCI
- 86.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- AstraZeneca
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- aspirin, primary prevention, cardiovascular disease, cardiovascular events, older adults, gastrointestinal bleeding, bleeding risk, cardiovascular mortality, myocardial infarction, stroke, serious adverse events, ARRIVE trial, enteric-coated aspirin, placebo comparison, risk stratification, bleeding risk assessment, secondary prevention, cardiovascular risk
- MeSH terms
- Aged, Aspirin, Double-Blind Method, Female, Gastrointestinal Hemorrhage, Humans, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction, Platelet Aggregation Inhibitors, Risk Factors, Proportional Hazards Models, Stroke, Intention to Treat Analysis
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