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Lancet. 2018 Sep 22;392(10152):1036-1046. doi: 10.1016/S0140-6736(18)31924-X. Epub 2018 Aug 26.

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.

Author information

1
Brigham and Women's Hospital, Department of Medicine, Division of Aging, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA. Electronic address: jmgaziano@partners.org.
2
Sardenya Primary Health Care Center, EAP Sardenya-Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
3
Bayer HealthCare LLC, Whippany, NJ, USA.
4
Società Italiana di Medicina Generale, Florence, Italy.
5
Department of Cardiology, Angiology, Nephrology and Intensive Care Medicine, Vivantes Neukoelln Medical Center, Berlin, Germany.
6
Department of Translational Science & Molecular Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, USA; Vascular Neurology Program, Mercy Health Hauenstein Neurosciences, Grand Rapids, Michigan Grand Rapids, MI, USA.
7
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
8
Department of Epidemiology and Medicine, University of Florida Health Science Center, Gainsville, FL, USA.
9
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
10
Internal Medicine, Complutense University, Head of the Hypertension Unit, 12 de Octubre Hospital, Madrid, Spain.
11
Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
12
IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Cardiovascular Research, IRCSS, Milan, Italy.

Abstract

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.

PMID:
30158069
DOI:
10.1016/S0140-6736(18)31924-X
[Indexed for MEDLINE]

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