Daily Low Dose Aspirin Fails to Extend Healthy Life Spans in Older Patients

Aspirin is arguably a calorie restriction mimetic, able to spur some of the same beneficial cellular stress responses that are activated by low nutrient levels. Calorie restriction itself, practiced over the long term, does not have a very large effect on human life span. Given the existing demographic data, a gain of even five years of life would be very surprising. Further, it is well established that the life extension resulting from calorie restriction scales down as species life span scales up. Mice live up to 40% longer on calorie restricted diets, but we humans certainly don't.

Aspirin has other effects besides increasing cellular stress responses, some good and some bad. Either no effect, a very small reduction, or a very small gain in life span are all plausible predictions for the outcome of a study on use of aspirin in older patients. The initial results from this study of aspirin cannot be used to discuss overall life span, but the data does show no gain in a common measure of healthy life span, free from disability. Nonetheless, this is a result that can be compared to studies in short-lived species in which it does modestly extend healthy life. This is more or less exactly what we should expect to see from most of the current crop of calorie restriction mimetic drugs. It would be surprising to see large effects on life span in humans, given what is known of the underlying mechanisms, and given that most of these compounds are only mildly mimetic of the actual calorie restriction response.

The large ASPirin in Reducing Events in the Elderly (ASPREE) trial is intended to determine the risks and benefits of daily low-dose aspirin in healthy older adults without previous cardiovascular events. Initial results show that aspirin did not prolong healthy, independent living (life free of dementia or persistent physical disability). Risk of dying from a range of causes, including cancer and heart disease, varied and will require further analysis and additional follow-up of study participants.

ASPREE is an international, randomized, double-blind, placebo-controlled trial that enrolled 19,114 older people (16,703 in Australia and 2,411 in the United States). The study began in 2010 and enrolled participants aged 70 and older; 65 was the minimum age of entry for African-American and Hispanic individuals in the United States because of their higher risk for dementia and cardiovascular disease. At study enrollment, ASPREE participants could not have dementia or a physical disability and had to be free of medical conditions requiring aspirin use. They were followed for an average of 4.7 years to determine outcomes.

In the total study population, treatment with 100 mg of low-dose aspirin per day did not affect survival free of dementia or disability. Among the people randomly assigned to take aspirin, 90.3 percent remained alive at the end of the treatment without persistent physical disability or dementia, compared with 90.5 percent of those taking a placebo. Rates of physical disability were similar, and rates of dementia were almost identical in both groups.

The group taking aspirin had an increased risk of death compared to the placebo group: 5.9 percent of participants taking aspirin and 5.2 percent taking placebo died during the study. This effect of aspirin has not been noted in previous studies; and caution is needed in interpreting this finding. The higher death rate in the aspirin-treated group was due primarily to a higher rate of cancer deaths. A small increase in new cancer cases was reported in the group taking aspirin but the difference could have been due to chance. As would be expected in an older adult population, cancer was a common cause of death, and 50 percent of the people who died in the trial had some type of cancer.

The researchers also analyzed the ASPREE results to determine whether cardiovascular events took place. They found that the rates for major cardiovascular events - including coronary heart disease, nonfatal heart attacks, and fatal and nonfatal ischemic stroke - were similar in the aspirin and the placebo groups. In the aspirin group, 448 people experienced cardiovascular events, compared with 474 people in the placebo group.

Link: https://www.nia.nih.gov/news/daily-low-dose-aspirin-found-have-no-effect-healthy-life-span-older-people