Aspirin was derived from the bark of a willow tree with analgesic and anti-fever benefits that were initially used 35 centuries ago. In 1897 Felix Hoffman synthesized aspirin and used it on his father who had rheumatism. Nobel Prize winner John Vane first described aspirin’s mechanism of action. He proved aspirin inhibits the enzyme cyclooxygenase that facilitates the production of prostaglandins, which are responsible for fever and inflammation. Incidentally, prostaglandins have protective effects on the stomach and kidneys.
About 130 million US adults take aspirin for cardiovascular prevention, 23% of them for primary prevention, meaning those who do not have confirmed heart disease. The benefit of aspirin for secondary prevention of cardiovascular disease is well established with a low dose of aspirin. There is no benefit of giving a high dose of aspirin over a low dose of aspirin, and this was confirmed in multiple studies.
Aspirin requires acetylation to become active and this may be the plausible reason for using higher dose in obese patients.
There is some evidence that in obese patients, a higher dose of aspirin is needed, but that is somewhat controversial.
Be that as it may, several recent studies questioned the benefit of aspirin for the primary prevention of cardiovascular disease. The primary reason for this skepticism is related to the side effects, the primary side effect being internal bleeding. In the study ASCEND that was published in 2018 in the New England Journal of Medicine, the incidence of cardiovascular events were 1.1% lower in the aspirin group than in the placebo group and in the bleeding events 0.9% higher in the aspirin group. Among the internal bleeding, 41.3% were from gastrointestinal events, 21.1 % were sight threatening bleeding events in the eye, 17.2 % were intracranial events, and 20.4 % were bleeding events in other sites, based on this ASCEND study.
The incidence of nonfatal bleeding was higher in the aspirin group. Based on this, primary prevention of cardiovascular disease in those who do not have any known cardiovascular disease should be limited to patients between the age of 50 and 70 years. The risk of bleeding is higher after the age of 70 and this risk-to-benefit ratio is blurred with a potential for risk outweighing the benefit. According to the US Preventative Services Task Force, aspirin is not recommended for patients below 50 years of age or those above 70 years. In the age group of 50-59 years, aspirin is recommended for the prevention of cardiovascular disease and the prevention of colorectal cancer, per US Preventive Services Task Force. The benefit of decreased risk of colorectal cancer is noted once aspirin is taken for more than 10 years. The aspirin needs to be given to patients who are not at increased risk of bleeding and who have a life expectancy of at least 10 more years. For patients between the ages of 60-69 years, aspirin can be given if they are not at increased risk of bleeding, have a life expectancy of at least 10 more years, and are willing to take a low dose of aspirin for at least 10 years. Patients meeting these qualifications are likely to benefit.
Again there is no benefit of using high dose aspirin over low dose aspirin, and the risk of bleeding increases as the dosage increases.
In summary, aspirin is a safe drug with definite benefits in the age groups of 50-69. Beyond 70 years of age, the benefit of aspirin for the primary prevention of cardiovascular disease is debatable because of the risk of internal bleeding
Adi B. Reddy, MD, FACG, AGAF
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