In older patients, daily aspirin use can lead to fatigue and functional decline

Low-dose aspirin is very effective for prevention of cardiovascular disease. Typically, low-dose is considered to be 75-100 mg of aspirin daily, depending on the country. Even at these low-doses, aspirin is not without risk which primarily is manifest as a risk of gastrointestinal blood loss. A recent large clinical trial validates the concept that aspirin at low-doses causes damage to the gastrointestinal (GI) tract.1 The ASPREE (Aspirin in Reducing Events in the Elderly) clinical trial randomized 19,114 people older than 65 years, taking 100-mg of daily aspirin, and demonstrated that aspirin use was associated with a 20% higher risk of anemia compared with placebo. Anemia in older people—likely caused by aspirin-induced GI bleeding, is tied to functional decline, fatigue, and higher mortality. The findings therefore reinforce new guidelines that promote aspirin as a tool for secondary—not primary—prevention of cardiovascular disease in older people, and support regular monitoring of hemoglobin in patients who use the drug.

The ASPREE trial, a large prospective trial, validates what has been observed for many years with low-doses of aspirin in smaller studies. I have previously conducted a prospective dose finding study with aspirin to endoscopically assess whether there might be an orally-administered aspirin dose that is without GI adverse effects. We found that aspirin doses as low as 10 mg daily cause gastric ulcers.2 However, that dose (10 mg) is suboptimal for prevention of platelet clotting. Thus, there is likely no orally administered aspirin dose that is an effective anti-platelet agent that is without GI adverse effects.

Since all doses of aspirin appear to have GI side-effects, should aspirin be withheld because of a concern of GI bleeding? Aspirin should definitely not be withheld because of GI blood loss concerns. Aspirin’s benefits for prevention of cardiovascular disease and strokes far outweigh its GI risks. In this context, it is far more important to protect the heart and brain at the expense of the GI tract. GI morbidity derived from long-term low-dose aspirin use is much less than the cardiovascular morbidity and mortality seen when aspirin is withheld.

Since many patients will need to take aspirin for cardiovascular and cerebrovascular benefits, what might be strategies to decrease the incidence of GI bleeding? One approach is a proton pump inhibitor (PPI)-aspirin combination or PPI co-administration with aspirin. However, the PPI only protects against aspirin-GI blood losses in the proximal GI tract and does not protect against the greater component of more extensive small intestinal and colonic blood losses with aspirin. Another approach that has been recently commercially developed to reduce GI injury is Vazalore (81 mg and 325mg aspirin) a newly introduced (over-the-counter) OTC aspirin-lipid formulated capsule.

How should clinicians monitor gastrointestinal blood loss in patients taking long-term low-dose aspirin at high-risk for aspirin-induced GI bleeding? The time interval that hemoglobin (Hgb) should be followed has not yet been defined by guidelines and will likely be individualized. Until guideline assistance is developed, however, Hgb assessment intervals in the range of 3-12 months seem reasonable.

1 JAMA. June 28, 2023. doi:10.1001/jama.2023.11954

2 Cryer B and Feldman M. Effects of very low doses of daily, long-term aspirin therapy on gastric, duodenal and rectal prostaglandins an on mucosal injury in healthy humans. Gastroenterology 1999;117:17-25.