Aspirin in primary prevention of atherosclerosis: a shrinking mourning skin

Louis MONNIER, Clinical Research Institute, Montpellier

Despite important advances in the use of high-potency statins and new antiplatelet or antithrombotic treatments, low-dose aspirin continues to be an effective treatment in the secondary prevention of cardiovascular diseases and events (relative risk reduction of the order of twenty%). On the other hand, the prescription of aspirin in primary prevention in subjects who have never had a cardiovascular accident has been the subject of debate for several years.

Thus, the recommendations of the USPSTF (US Preventive Services Task Force) of 2016 had already formulated a series of reservations regarding the prescription of aspirin in primary prevention. The most striking were the following: lack of efficacy in subjects younger than 50 years or whose age is ≥ 70 years; recommended prescription between 50 and 59 years in subjects with a risk of vascular accident ≥ 10% in the next 10 years, with a life expectancy of at least 10 years and without risk of hemorrhage; selective prescription between 60 and 69 years and reserved for correctly identified subjects. These recommendations published in 2016 were based on a systematic review of 11 large primary prevention clinical trials with aspirin doses generally ≤ 100 mg/day. However, these trials had been carried out at a time when control of plasma lipids and blood pressure was far from optimal and tobacco use was quite widespread. In 2022, therefore, it was necessary to update these recommendations. This was achieved by expanding the analysis to 13 prevention trials, i.e. 161,680 subjects, in order to better assess the benefit/risk ratio of aspirin treatment. Results The most interesting are given by a microsimulation model produced from the tests included in a systematic analysis. Benefits were judged on gains (or losses?) in life expectancy (expressed in years of life gained or [perdues ?] per 1,000 inhabitants) and the gain in life expectancy with good quality, also expressed in net years gained with good quality of life. Results were then reported by sex and age group according to whether aspirin treatment had been started between 40-49 years, 50-59 years, 60-69 years, and 70-79 years. The results can be summarized as follows (table): • Aspirin use in men and women in the age group 40-59 years with a risk of cardiovascular events ≥ 10% at 10-year maturity leads to an extension of life expectancy but which, however, remains very modest. Since the results are expressed in years gained per 1000 people, we have converted them for at least two of them into patient days to make them more readable. Thus, for men between 40 and 49 years old, with a risk of cardiovascular accident ≥ 20% in the next 10 years, the gain in life expectancy after starting aspirin treatment is only 19 days. For a woman between the ages of 40 and 49, with a risk of stroke equal to at least ≥ 10% in the next 10 years, this same gain is only 4 days. The gain in quality of life during the years (gained?) or rather the days gained is of the same order of magnitude. It must be believed that the authors of the article did not dare to convert the 1,000 patient-years into patient-days in order not to show too clearly the great modesty of the results. • In the age group 60 to 69 years, the results are discordant, ranging from a again very modest gain in quality or extension of life expectancy to a reduction depending on the level of risk when starting aspirin. In this age group, due to life expectancy itself, it is in all cases a loss that is observed, even if it is extremely modest (1 to 2 days on average per patient). • Finally, beyond 70 years, a loss in life expectancy in terms of duration and quality of life has been observed, although it remains very modest (a few days at most). • When considering the hemorrhagic risk, it increases with aspirin treatment, both in digestive hemorrhages (+58%) and in cerebral hemorrhages (+31%). Bleeding events generally occur soon after the start of aspirin therapy. Given that the risk of bleeding doubles every 10 years over the age of 60, and given that aspirin does not offer any benefit in terms of primary prevention at the cardiovascular level, it is quite certain that advanced age is a contraindication to starting aspirin therapy. Summary table of the effect of aspirin in the primary prevention of cardiovascular diseases. The gains or losses in life expectancy are in all cases very small, even when considered statistically significant. For example, the greatest gain in life expectancy was 19 days, observed in men aged 40 to 49 years and with a ≥ 20% risk of suffering a cardiovascular event in the next 10 years. Overall Conclusion The 2022 USPSTF recommendations are made in light of these very simple observations: • In subjects aged 40 to 59 years, aspirin can only be used in primary prevention in persons with a risk of cardiovascular event ≥ 10% at expiration of 10 years . However, the convenience of starting this type of treatment is at the discretion of the treating physician. However, this treatment is not recommended for subjects at risk of bleeding. • In subjects 60 years of age or older, aspirin treatment should not be initiated as part of primary prevention. Ultimately, these 2022 recommendations are more restrictive than the 2016 ones; they leave little room for the use of aspirin in primary prevention. The USPSTF specifies that the decision to use aspirin in primary prevention should always be left to the discretion of health professionals. In addition, the Harvard University authors who wrote the USPSTF’s post-study editorial note that aspirin is still too often used inappropriately in primary prevention. Posted by Practical Diabetology

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