Fight Aging!

The back and forth over whether regular aspirin use is beneficial continues with the publication of results from analysis of a large patient population that show a 15% reduction in all cause mortality in patients using aspirin. This contradicts the much smaller (but still large in and of itself) ASPREE clinical trial, in which patients using aspirin exhibited a small increase in mortality in comparison to their peers. As in that earlier study, the data here strongly suggests that benefits and risks vary with patient characteristics, such as whether or not a patient is overweight.

Aspirin is thought to be a weak calorie restriction mimetic, in that it can produce benefits via upregulation of autophagy to some degree, but it also reduces inflammation and blood clotting, among other effects. That reduction in inflammation is probably the most important benefit. Other studies suggest that the use of NSAIDs like aspirin reduces risk of Alzheimer's disease, which may well be the case for any long-term anti-inflammatory treatment, given the strong role played by chronic inflammation in that condition.

This sort of contradictory evidence is characteristic of medications with small effects. One would imagine that senolytics, capable of producing a larger and more reliable reduction of chronic inflammation in old people via clearance of senescent cells, could be put through much the same sort of clinical trials and emerge on the other side with far less ambiguity in the outcome for patients. We shall see whether or not this is the case in the years ahead, of course. But the point is that large effects tend to lead to consistent data, while inconsistent data is a hallmark of small effects.

Association of Aspirin Use With Mortality Risk Among Older Adult Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

This cohort study found that aspirin use among individuals 65 years and older was associated with a lower risk of mortality. This observation was consistent across all causes of mortality, i.e., all-cause, cancer, gastrointestinal cancer, and colorectal cancer (CRC); however, the greatest reduction in risk was noted for CRC mortality among individuals who used aspirin 3 or more times per week. Additionally, our exploratory analyses investigating the potential associations among aspirin use, BMI, and mortality risk suggest that the efficacy of aspirin as a cancer preventive agent may be associated with BMI. Participants in the PLCO Cancer Screening Trial who were underweight (i.e., BMI less than 20) had no observable benefit associated with aspirin use, while those with BMI 20 or higher were associated with reduced mortality risk, particularly with aspirin use 3 or more times per week. reduced risk of CRC mortality was only associated with individuals with BMI 20 to 29.9 who reported aspirin use 3 or more times per week.

The efficacy of prophylactic aspirin use for prevention of cancer incidence and mortality has been debated; however, the most evidence from prospective cohorts and secondary analyses from clinical trials indicates a protective association with aspirin use. A 2016 systematic analysis of primary and secondary cardiovascular prevention trials found reduced CRC incidence 10 to 19 years after aspirin use initiation. This association persists among investigations of aspirin use and cancer mortality.

These observations are in contrast with data from the ASPREE trial. However, the interpretation of the ASPREE results is limited owing a lack of an association of aspirin with cancer and CRC incidence and the short duration of follow-up. With additional follow-up, an association of aspirin with lower cancer incidence and death may have emerged. In addition, a 2018 combined analysis of the NIH-AARP Diet and Health Study and the PLCO Cancer Screening Trial reported decreased risk of all-cause, cancer, and cardiovascular mortality associated with daily aspirin use. However, a dosage that exceeded 1 per day was associated with an increased risk of mortality. These data also did not account for effect modifications by BMI on mortality risk. Previous studies have also found that variables, such as BMI, are associated with the efficacy of prophylactic aspirin. In a 2012 study of the Cancer Prevention Study-II Nutrition Cohort, individuals with prediagnostic BMI 30 or higher were associated with increased risk of all-cause and CRC death. A similar association was demonstrated across several other cohort and case-control studies, cancers, and causes of death.

The observation that BMI may be associated with efficacy of aspirin in individuals 65 years and older is notable; however, our findings require further confirmation. Increasing rates of overweight and obesity globally may substantially alter the population-based efficacy of cancer prevention prophylatics. Studies have suggested that aspirin has reduced effectiveness as a primary prevention modality among individuals who are obese owing to decreased bioavailability and antithrombotic efficacy; however, this study did not find an association of overweight or obesity with decreased efficacy. Therefore, although aspirin use is associated with benefit as a cancer preventive agent, the changing characteristics of the global population may alter its efficacy and must be considered along with age and risk of bleeding before recommending aspirin for cancer prevention.