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Low-dose aspirin does not prolong the disability-free survival of healthy people over the age of 70, even among those with the highest risk of cardiovascular disease. The last minute results of the ASPREE trial are presented today at the 2019 ESC Congress concurrently with the World Congress of Cardiology (1).
Christopher Reid, a professor at Curtin University in Perth, Australia, said on behalf of ASPREE investigators: "An ever-increasing number of people are reaching the age of 70 without any reported cardiovascular disease. There is a need to improve risk prediction methods – identify those who could benefit from low dose daily aspirin.
European guidelines on the prevention of cardiovascular disease do not recommend aspirin to people without cardiovascular disease because of the increased risk of major bleeding (2). This opinion was then confirmed by the results obtained in patients at moderate risk (ARRIVE), (3) in diabetic patients (ASCEND), (4) and in people over 70 (ASPREE), who demonstrated that the increased risk of bleeding was greater than the modest CVD risk reductions (5).
The main finding of the ASPREE randomized trial was that in people 70 years of age and older without CVD, there was no effect of 100 mg aspirin daily on the composite primary endpoint of survival without disability (defined in those who did not reach a primary score). primary endpoint of dementia or persistent physical disability or death) (6) The primary endpoint was chosen to reflect the reasons for prescribing a preventative drug in a population of older people otherwise healthy.
This analysis examined whether the findings regarding the primary endpoint of disability-free survival could vary with the level of risk of CVD baseline. Analyzes were also conducted on secondary end-point mortality, major bleeding and CVD prevention criteria (defined as fatal coronary artery disease, nonfatal myocardial infarction, fatal or non-fatal stroke, or hospitalization). for heart failure).
The researchers calculated the 10-year risk estimates of CVD for the 19,114 ASPREE participants using the Framingham score (up to age 75) and the combined cohort risk equations for atherosclerotic cardiovascular disease ( ASCVD) (up to 79 years) and divided them into thirds. In the absence of CVD risk scores available beyond the age ranges specified in the equations, they also ranked participants according to the presence of 0 to 1, 2 to 3, or more than 3 CVD risk factors. The overall rates of disability-free survival, mortality, major bleeding and CVD were examined for each risk group and the results were compared for those treated with aspirin or placebo.
For participants in the lower third of the CVD risk, according to the Framingham and ASCVD scores, there was no disability-free survival or cardiovascular benefit of aspirin. This group also had the highest risk of bleeding.
In contrast, in patients with the highest third risk of CVD, according to the Framingham and ASCVD scores, the cardiovascular event rates on aspirin were significantly lower, with similar bleeding. The risk ratios for CVD reduction with the aspirin version of the placebo were 0.72 (95% confidence interval). [CI] 0.54-0.95) for the high-risk group according to the Framingham score and 0.75 (95% CI 0.58-0.97) for those defined at high risk by the ASCVD equations.
However, this reduction in CVD did not translate into a significant improvement in disability-free survival. The hazard ratios for aspirin-free survival versus aspirin versus placebo were 0.86 (95% CI: 0.62-1.20) for the high-risk group rated by the Framingham score and 0.89 (95% CI: 0.62-1.28) for those considered high risk according to the ASCVD equation. .
Prof Reid said, "The findings point out that the benefit-risk balance for the use of aspirin in healthy older men and women varies with cardiovascular risk levels. Reducing the number of CVD events in high-risk groups using current stratification methods does not identify individuals in whom this benefit results in longer incapacitated survival. "
The ASPREE longitudinal follow-up study will explore new ways to identify groups at increased risk of CVD, beyond the use of conventional risk factors and current forecasting models. Information on genetics and biomarkers will be included in the ASPREE biobank.
Professor Reid concluded: "According to the results of the main ASPREE trial, low-dose daily aspirin can not be recommended in healthy people over the age of 70, even in those with the greatest risk of CVD.The current analysis indicates that more refined methods are needed a subgroup that could benefit from preventive therapy ".
References and notes
(1) The abstract "A risk-based approach to the role of aspirin in reducing cardiovascular risk in a cohort of healthy older people" will be presented in the session "Late-Stage Science in Cardiovascular Pharmacology" "Saturday, August 31 from 11:00 to 12:30 (Paris time). in the room London – village 2.
(2) 2016 European Guidelines on the Prevention of Cardiovascular Disease in Clinical Practice. Eur Heart J. 2016; 37: 2315-2381. doi: 10.1093 / eurheartj / ehw106.
(3) Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce the risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): randomized, double-blind, placebo-controlled trial. Lancet. 2018; 392: 1036-1046. doi: 10.1016 / S0140-6736 (18) 31924-X.
(4) Bowman L, Mafham M, Wallendszus K, et al. Effects of aspirin on primary prevention in people with diabetes mellitus. N Engl J Med. 2018; 379: 1529-1539. doi: 10.1056 / NEJMoa1804988.
(5) McNeil JJ, Wolfe R, Woods RL et al. Effect of aspirin on cardiovascular events and bleeding in healthy elderly people. N Engl J Med. 2018; 379: 1509-1518. doi: 10.1056 / NEJMoa1805819.
(6) McNeil JJ, Woods RL, Nelson MR et al. Effect of aspirin on disability-free survival in healthy elderly people. N Engl J Med. 2018; 379: 1499-1508. doi: 10.1056 / NEJMoa1800722.
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