Unexpected benefits of a well-known wonder drug

By Naveed Saleh, MD, MS
Published October 2, 2020

Key Takeaways

Although it used to be known as “the wonder drug that works wonders,” we now know that aspirin can be a very dangerous drug largely because it increases the risk of internal bleeding—especially in older adults who drink alcohol, those with a history of ulcers, or those taking anticoagulants. In such populations, the risk of taking aspirin likely outweighs the benefits. Bleeding risk even occurs in those taking low-dose 81-mg formulations (ie, baby aspirin), not just from the regular strength dose of 325 mg.

In people who are at lower risk for bleeds, though, aspirin may provide many benefits that could outweigh the drawbacks, per the experts. These benefits extend well past the commonly known benefits of pain relief and stroke prevention. 

Here are five of aspirin’s unexpected benefits—for neurocognition, pregnancy, and cancer.

Dementia prevention in some

Preclinical studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) could prevent the onset of Alzheimer disease, a hypothesis that’s been supported by various observational studies conducted since the 1990s. 

Based on the results of a meta-analysis of cross-sectional, retrospective, or prospective observational studies, the researchers found that NSAID exposure decreased risk of Alzheimer disease. Drawing from 11 studies that met inclusion criteria, the combined risk estimate for the development of Alzheimer disease was 0.51 with NSAID exposure. In prospective studies, this risk was 0.74, and in studies reporting a duration of aspirin use of 2 or more years, the risk was 0.42.

More recent large, NIH-sponsored clinical trials examining the effects of daily aspirin use in healthy adults aged 65 years or greater provide an important caveat, though. Aspirin use likely doesn’t help those who are healthy, without a supported indication such as a history of stroke or heart attack. It remains to be elucidated whether aspirin proffers any protective effects if taken before the age of 65.

Preeclampsia prevention in some

In 1985, evidence emerged that low-dose aspirin taken during pregnancy could exert a protective effect against preeclampsia. Ever since that time, however, the subject has been controversial, despite a recent trend of taking aspirin while pregnant.

Results from a recent review published in the journal Drugs indicated that low-dose aspirin is effective as secondary prevention of preeclampsia in patients with a history of preeclampsia; however, the effect in those at high risk of preeclampsia but without such history remains to be elucidated. High-risk patients could be given this treatment during the first trimester of pregnancy, but screening procedures need to be researched, the authors noted.

Aspirin efficacy for preeclampsia prevention is dose-dependent, with an optimum dosage—between 75 mg/day and 150 mg/day—to be determined.

As for a mechanism, the authors suggested that in preeclampsia, “platelet TXA2 increases significantly, whereas prostacyclin drops sharply. This imbalance is present from 13 weeks of gestation in patients at high risk. TXA2/PGI2 imbalance can be reversed by 2 weeks of treatment with low-dose aspirin, which inhibits TXA2 secretion, and thus platelet aggregation, without altering secretion of endothelial prostacyclin (PGI2), thereby favoring systemic vasodilatation.”

Preterm birth

In another NIH-sponsored, large-scale clinical trial involving first-time mothers from various countries, researchers tested the effect of daily low-dose aspirin on the prevention of preterm birth starting in the first trimester (as early as the sixth week of pregnancy) and extending up through either the 36th week of pregnancy or until birth.

Publishing in The Lancet, the investigators noted that women taking low-dose aspirin were 11% less likely to deliver prematurely (before 37 weeks) compared with those in the control group. Furthermore, preterm birth occurred in 11.6% of women taking aspirin compared with 13.1% in the control group.

In other results, the researchers found that aspirin use lowered the risk of early preterm delivery (birth before 34 weeks) by 25%, with early preterm birth occurring in 3.3% of the aspirin group vs 4% in the control group. Aspirin also decreased perinatal mortality, defined as stillbirth or newborn death in the first week of life. No differences in preeclampsia rates were noted.

Lung cancer

Low-dose aspirin use for the chemoprevention of lung cancer is a hot topic. Certain randomized trials have demonstrated beneficial effects of long-term, low-dose aspirin use, although population-based studies—particularly among women—have failed to support this association.

Results from a recent population-based study identifying aspirin-use and lung-cancer data representing 12,969,400 people demonstrated that doses of ≤ 100 mg daily taken at least 2 days per week was linked to a significant decrease in lung cancer risk. Specifically, lung cancer risk reductions were 4%, 6%, and 11% following usage periods of 5 to 6 years, 7 to 8 years, and 9 years, respectively.

Per the JAMA study, the benefit of aspirin use for more than 5 years in the prevention of lung cancer—albeit modest—was most pronounced in elderly participants and those without diabetes.  

As for a mechanism, the authors suggested that “The antineoplastic effect of aspirin may be associated with the inhibition of cyclooxygenase-1 (COX-1)–mediated platelet activation. Inhibition of arterial thrombosis by aspirin impedes the development and progression of certain cancers. Cyclooxygenase-2 is known to be involved in the inflammatory process, and inhibition of COX-2–derived prostaglandin E2 formation by aspirin induces inhibition of cell proliferation and reduction of angiogenesis and immunomodulation through the production of lymphocytes in the peripheral blood. Cyclooxygenase-2 is expressed at high levels in human lung cancer tissue, especially in adenocarcinoma.”

Colorectal cancer

A plethora of data exist to support the use of aspirin as a chemopreventive strategy. These data are so compelling that they support the use of this intervention as an indicated recommendation, per the authors of a review article published in Best Practices & Research: Clinical Gastroenterology.

According to the authors, “there is clear evidence that aspirin in doses as low as 325 mg per day reduces colorectal cancer risk. There is also strong evidence from secondary analyses of cardiovascular trials that daily doses as low as 75 mg per day may be effective. In particular, the emerging data that aspirin may reduce risk of [a] panoply of cancers suggest that an overall consideration of aspirin’s benefits for all cancers and vascular disease may dominate concerns about potential hazards at either dose.”

“Moreover,” they added, "incorporation of potential benefits associated with the development of an efficacious and cost-effective means of reducing the GI risks of long-term aspirin use (eg, concurrent administration of gastroprotective agents) will also likely require future consideration in defining optimal dosing.”

The authors also suggested that the relative cost-effectiveness of aspirin compared with screening colonoscopy/sigmoidoscopy further supports the use of aspirin as a preventive measure.

What’s the proposed mechanism for aspirin’s effectiveness against colorectal cancer? Besides targeting COX-dependent mechanisms underlying cancer processes, as noted above, aspirin may also stymie COX-independent pathways involved in tumor pathogenesis. Furthermore, aspirin could boost the apoptosis of tumor cells. 

In the case of experiments assessing the antineoplastic effects of aspirin on COX-independent pathways, however, in vitro studies involved much higher doses than possible in vivo, which could be a significant limitation. Due to binding by proteins in humans, peak plasma levels of aspirin are reached at 300 mg/day; concentrations of aspirin in in vivo studies were much higher.

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