Aspirin is once again in the headlines, prompted by New England Journal of Medicine reports suggesting that people aged 70 years and older obtain no benefit and perhaps experience harm in the form of increased bleeding and increased death from cancer on low-dose aspirin. This adds to the decades-long debate on whether aspirin is beneficial as a preventive measure against cardiovascular events such as heart attack in which a blood clot forms on top of inflamed atherosclerotic plaque in the coronary arteries. Unlike many other studies that are observational and therefore virtually useless, these studies are prospective and randomized against placebo, studies that bear greater weight with conclusions that are more certain to establish cause-effect relationships.
There is no question that people who have stents implanted in their coronary arteries, have bypass grafts, or have suffered a heart attack experience reduced risk of recurrent coronary events with aspirin, so-called “secondary prevention.” The tougher question comes in whether aspirin provides any benefits in primary prevention, i.e., lower-risk people without stents, bypass grafts, or prior heart attack.
The three reports originated with the ASPREE trial of 19,000 Australians and Americans age 70 years or older, randomized to aspirin 100 mg per day vs. placebo: no difference in cardiovascular death or cardiovascular events (fatal heart attack, non-fatal heart attack, stroke) over nearly 5 years, with about a 1.5% increase in bleeding (e.g., intracranial bleeding, gastrointestinal hemorrhage).
Previous clinical trials (prospective, randomized to aspirin vs. placebo) in broader populations examining whether low-dose aspirin (typically 81-100 mg, a baby aspirin) likewise mostly suggest no benefit, much in line with these recent reports in people 70 years or older. The recent ARRIVE trial of 12,000 participants, for instance, randomized to aspirin 100 mg vs. placebo, showed no benefit and a modest increase in bleeding from aspirin.
People who are hypercoagulable, i.e., have more platelet activation, higher levels of the blood clotting protein fibrinogen, have greater inflammation and insulin resistance, do indeed appear to gain a teensy-weensy benefit by taking low-dose aspirin, as shown in the recent ASCEND Study of 15,000 people with type 2 diabetes (i.e., people we know are inflamed, insulin resistant, nearly all overweight or obese, have greater platelet activation and fibrinogen levels) randomized to aspirin 100 mg per day or placebo: about a 1% reduction in cardiovascular events over 7 1/2 years (i.e., 0.13% reduction per year) and 1% increase in bleeding—hardly headline-worthy.
Let’s step back for a moment and take a look at the broader landscape. National dietary guidelines advocate limiting total and saturated fat, increased consumption of whole grains, and sugar in moderation, a lifestyle that has been associated with a dramatic surge in weight gain/overweight/obesity, epidemic levels of type 2 diabetes and pre-diabetes, autoimmune inflammation, hypercoagulability, and other “diseases of lifestyle.” In other words, dietary guidelines have created a population-wide hypercoagulable state with the most hypercoagulable obtaining about 1/10th of one percent per year reduction in cardiovascular events on aspirin and about the same risk of hemorrhage into the brain or gastrointestinal tract.
These most recent reports involving treatment randomization, large numbers of participants, with extended follow-up periods also counter a handful of previous observations suggesting a very small reduction in colorectal cancer on low-dose aspirin. ASPREE suggested about a 1% increase in cancer deaths (though no difference in cancer incidence).
Is aspirin a miracle drug for preventing cardiovascular events? Hardly. A 1/10th of one percent per year reduction in cardiovascular events in higher-risk hypercoagulable people at the cost of serious hemorrhage, sometimes fatal, is, in my mind, no benefit at all. And, putting all the evidence on cancer incidence together, it looks like aspirin likewise has little to no benefit in reducing colon cancer risk.
So much time and effort has been devoted to exploring a drug that yields so little in the way of preventive effects in the broad population. My advice: Eat healthy, as we do in the Wheat Belly and Undoctored lifestyles, address common nutritional deficiencies remaining in the wake of grain elimination and caused by modern lifestyles, and make a concerted effort to cultivate healthy bowel flora. Now THERE’s a package of life- and health-changing strategies, unlike the little to no protection afforded by low-dose aspirin.