Aspirin Use Fails to Postpone Disability and Improve Survival in Older Individuals

Aspirin is arguably a calorie restriction mimetic, in that it boosts the operation of the cellular maintenance processes of autophagy to some degree. Increased autophagy is a feature of many of the interventions, such as calorie restriction, that slow aging in various animal models. Aspirin can extend life in short-lived species. The fact that an ongoing trial shows it to do no such thing in humans is just one more of the many pieces of evidence to demonstrate that short-lived and long-lived species have a very different plasticity of longevity in response to upregulation of stress response systems such as autophagy. The effect size of benefits resulting from aspirin in old humans is small enough to be overwhelmed by harmful side-effects in a sizable fraction of the population - this is exactly the sort of marginal medical technology that should be sidelined in favor of better approaches to the treatment of aging.

European guidelines on the prevention of cardiovascular disease (CVD) do not recommend aspirin for individuals free from CVD due to the increased risk of major bleeding. This advice was subsequently supported by results in moderate risk patients (ARRIVE trial), diabetic patients (ASCEND trial), and in people over 70 (ASPREE trial), which demonstrated that modest reductions in CVD risk were outweighed by the increased bleeding hazard.

The primary finding from the ASPREE randomised trial was that in people aged 70 years or over with no known CVD, there was no effect of 100 mg of daily aspirin on the composite primary endpoint of disability-free survival (defined as those not reaching a primary endpoint of dementia or persistent physical disability or death). The primary endpoint was chosen to reflect the reasons for prescribing a preventive drug in an otherwise healthy elderly population.

The investigators calculated ten-year CVD risk probabilities at baseline for the 19,114 ASPREE participants using the Framingham score (up to 75 years) and the Hazard ratios for CVD reduction with aspirin version placebo were 0.72 for the group classified as high risk by the Framingham score and 0.75 for those defined as high risk by the ASCVD equations. However, this reduction in CVD did not translate to a significantly improved disability-free survival.

"The findings emphasise that the risk-benefit trade-off for aspirin use in healthy older men and women varies across levels of cardiovascular risk. It also indicates that the reduction in CVD events in the highest risk groups using current stratification methods does not identify individuals in whom this advantage translates into longer disability-free survival. Based on the results of the main ASPREE trial, daily low-dose aspirin cannot be recommended in healthy people over 70 - even in those at the greatest CVD risk. Today's analysis indicates that more refined methods are needed to pinpoint a subgroup who might gain from preventive therapy."