Nutrition Notes

New Research Questions Validity of Daily Aspirin for Primary Prevention

For years, select patient groups have been advised to take a daily aspirin to reduce risk for cardiovascular and cerebrovascular events such as heart attack and stroke. However, recent research from the University of Alberta in Canada, published in Canadian Family Physician, indicates that among certain patient populations this advice may be doing more harm than good.

The article, “Acetylsalicylic acid for primary prevention of cardiovascular events,” joins a growing body of research upending and overturning much of the “conventional wisdom” that has guided allopathic medicine and mainstream nutrition for the past several decades. (For examples, previous blog posts have explored the numerous drawbacks of statin drugs, the pitfalls of low-sodium diets, the vindication of saturated fat in dairy, protein being beneficial, rather than harmful, for bone health, higher protein intakes having no adverse effect on kidney function, and the many beneficial roles for cholesterol.) So much of what we thought we “knew” has been called into question during the last few years, and it appears we can add the recommendation for daily aspirin therapy as a potential primary preventative to the list.    

The Canadian researchers examined data from three high-quality, placebo-controlled RCTs of aspirin dosed at 100 mg per day. Taken together, the three trials encompassed over 47,000 patients, including elderly individuals, those with diabetes, and those at moderate risk for cardiovascular (CV) disease. While the authors support continued daily aspirin therapy for secondary prevention, the findings put a kink in the works regarding primary prevention.

One of the trials they included followed over 12,000 patients at moderate CV risk taking either a daily aspirin or placebo. After five years, there were no differences in composite CV events or mortality, but there was a doubling in incidence of gastrointestinal bleeds. The second trial they looked at encompassed over 15,000 patients with diabetes (94% type 2). Here, compared to placebo, patients taking a daily aspirin had decreased composite CV events but increased fatal or major bleeding, with no difference in cancer incidence or all-cause mortality. The conclusion of this study, which was published in the New England Journal of Medicine, states it clearly: “The absolute benefits were largely counterbalanced by the bleeding hazard.”

The third trial they included encompassed over 19,000 elderly subjects (median age 74) was stopped for futility after 4.7 years. Subjects taking aspirin had no difference in composite CV events compared to those taking placebo, but they showed increases in fatal or major bleeds, cancer death, and all-cause mortality. The authors concluded, “The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo.” Not exactly the kinds of outcomes one would hope for.

According to Paul Fritsch, an author of the Canadian paper, “These aren’t nosebleeds or bleeding gums. These are major internal bleeds where the patients need hospitalization and perhaps a blood transfusion, so they’re of major clinical, and also personal, significance.” His co-author, Michael Kolber, noted, “This is the most significant practice-changing evidence to come out in the past year.”

The findings corroborate what was seen in a different systematic review and meta-analysis published earlier this year in JAMA: researchers looked at 13 trials encompassing over 164,000 patients free of CVD. In these individuals, aspirin use was associated with a lower risk of CV events (defined as cardiovascular death, nonfatal heart attack or nonfatal stroke), but an increased risk of major bleeding. A third 2019 meta-analysis came to the same conclusion: in patients with no known CVD, aspirin use reduced risk for heart attack but had no effect on stroke, CV death or all-cause mortality, and actually increased risk for major bleeding, gastrointestinal bleeding, and hemorrhagic stroke. Things aren’t looking so good for use of aspirin as a primary preventative.

To reiterate, data continue to confirm that aspirin’s anti-inflammatory and blood-thinning effects are beneficial for secondary prevention and in those with existing CVD. A meta-analysis that looked at 16 secondary prevention trials including 17,000 individuals at “high average risk” found that aspirin therapy resulted in a greater reduction in serious vascular events along with significant reductions in stroke and in coronary events, and a non-significant reduction in hemorrhagic stroke.

An aspirin a day might keep the doctor away for some patient populations, but others may be better served by taking aspirin only when needed for acute pain relief or some other short-term indication. As with so much in medicine and nutrition, there are no blanket recommendations that apply to everyone. Clinical judgments are best made on an individual basis, tailored to a patient’s unique history, situation, and goals.