A graphic of an oval pill behind an aspirin pill in front of an EKG waveform

Weekend Reads: Things Change, Even in Medicine

by Kevin Schofield


This weekend, we have two reads lined up, both relating to how long-standing and conventional medical practices change from time to time in the face of new information.

First, we have an updated recommendation from the American Medical Association (AMA) on the use of low doses of aspirin to reduce the risk of certain outcomes of cardiovascular disease, including heart attacks and strokes, as well as colorectal cancer. Prescribing aspirin in low doses has increased in popularity throughout the 2000s since evidence was published showing that it reduced risks from those diseases, and in 2016, the AMA issued a recommendation for doctors to prescribe it for their patients age 50 and older with an elevated risk of cardiovascular disease.

As with many medicines, aspirin has positives and negatives, and deciding whether a patient should take it is a delicate balancing act. We know much about its basic function: It inhibits the function of platelets, the component of blood that causes it to clot. Blood clotting is useful and important when it quickly stops a cut or wound from bleeding. However, it’s dangerous and harmful when it creates clots inside blood vessels that can travel through our bodies and ultimately block a vein or artery. That can lead to a deep vein thrombosis (DVT) in a leg, a heart attack if it happens in one of the major coronary arteries, or an obstruction that prevents blood from reaching part of the brain (known as an “ischemic stroke”). As we age and our arteries harden and narrow or get clogged up with plaque, the risk of blood clot obstructions increases, and aspirin has been shown to reduce the risk of such clots. 

On the other hand, as we get older, we also become more susceptible to weakened blood vessels. We need our blood to clot in order to protect us from a hemorrhagic stroke (a broken blood vessel in our brain) or an uncontrolled bleeding ulcer, both of which can be life-threatening. Aspirin not only increases these risks by impeding clotting, but it’s also been shown to inhibit the mucus in our digestive system that provides additional protection against ulcers.

The AMA’s recommendations for low-dose aspirin are based on doing the math for both the benefits and the risks. Specifically, it calculates how much longer people will likely live based on reducing their risk of heart attack or ischemic stroke, and how much less they are likely to live based on increasing their risk of a hemorrhagic stroke or digestive tract bleeding. If it’s a net positive, AMA recommends it; if it’s neutral or negative, it recommends against it. But this means understanding the different risks faced across age groups, as well as assessing an individual’s risk of cardiovascular disease.

What the researchers found, based on the latest studies, is that individuals age 40–59 who are at higher risk of cardiovascular disease derive a small net benefit from daily low-dose aspirin; those age 60–69 saw varying (but generally negative) benefit based upon the severity of their risk of cardiovascular disease; and for those 70 and older, low doses of aspirin were a net negative. Based on this finding, AMA’s new recommendation is that a daily regimen of low-dose aspirin is only recommended for individuals age 50–69 with increased risk of cardiovascular disease and low risk for bleeding. This is a significant retreat from the old guidance.

An interesting side discussion in the report relates to how the medical community evaluates whether someone has an elevated risk for conditions such as cardiovascular disease. Some parts are formulaic and directly data-driven, based on age and family history. But other parts are based on statistical analyses of large populations. For example, studies have shown that Black people tend to have a higher incidence of cardiovascular disease; this is often attributed to assumptions about diet and exercise that are supported by demographic studies. As a result, the standard evaluation for assessing cardiovascular risk assigns a higher risk to all Black persons. But in recent times, these kinds of demographic factors have been questioned more openly. The authors of this report chose to include the following discussion of this issue:

The risk prediction equations generally show higher risk for Black persons than White persons. The USPSTF recognizes that race is a social construct and an imperfect proxy for social determinants of health and the effects of structural racism. Concerns about calibration exist, with many external validation studies showing overprediction in broad populations (men and women across racial and ethnic groups). Limited evidence also suggests underprediction in disadvantaged communities that could lead to underutilization of preventive therapies. Clinicians should recognize that predictions of 10-year [cardiovascular disease] events using the Pooled Cohort Equations are estimates.

This points out that these kinds of sweeping race-based evaluations of disease risk fail in both directions: They can overestimate the risk for many people, such as assuming that all Black people are at higher risk of cardiovascular disease; but they can also underestimate the risk for individuals, such as assuming everyone of Asian heritage is at lower risk because demographic studies show that traditional Asian diets tend to be heart-healthy. As a result, an individual Black person could be mistakenly prescribed low-dose aspirin unnecessarily, and an Asian person could be denied the same prescription even though they could personally benefit from it. 

In all, this demonstrates how important it is for us to share with health care professionals the specifics of our own health situation so the right decisions can be made for us individually.

Aspirin Use to Prevent Cardiovascular Disease


The second report is about how doctors treat appendicitis. For decades, the conventional wisdom has been that the one and only proper treatment for appendicitis is an appendectomy: surgically removing one’s appendix. To the best of our knowledge, the appendix, true to its name, serves no important purpose in our bodies and can be removed without impairing any necessary bodily function. And while an infected and inflamed appendix is painful, one that subsequently bursts is life-threatening. But invasive surgery to remove an appendix also brings risks, including surgical complications, infections, post-operative recovery, and the risks that accompany the use of general anesthesia.

In the past several years, and most notably starting around 2014, some health care professionals have begun to challenge the conventional wisdom by treating appendicitis with antibiotics first in cases that appear to be less severe (and less imminent risk of a burst appendix). More recently, the health care profession has accumulated enough case data to be able to compare the outcomes of antibiotic treatment versus appendectomy. They have found that the vast majority of cases treated with antibiotics are successfully resolved, and only a small fraction of them ultimately require an appendectomy.

It’s important to remember, however, that science must be repeatable: A single research study is insufficient to cause the medical community to revise its practices. This report replicates earlier studies comparing the two treatments for appendicitis, and reaches the same conclusion: Antibiotics are, in most cases, successful.

What makes this particular study different is that it addressed a common weakness of this kind of research: how the study participants were selected. Some studies randomly assign patients to one of the two forms of treatment; others ask patients to choose whether they want the conventional treatment or the experimental one. If patients are assigned randomly, there are both ethical concerns and broader issues with removing patients’ control over their own health care; studies show that patients fare better when they are actively engaged in making decisions about their own health care. But allowing patients to choose the treatment creates the opportunity for “selection bias,” in which certain kinds of patients (e.g., risk takers, those with more years of education, or those with higher socioeconomic status) may be more likely to choose the experimental treatment, potentially skewing the results.

But in this study, the researchers did both: They had one cohort where the patients self-selected the form of treatment, and another cohort where treatment was randomly chosen for each patient. And they found that there were no differences in outcomes across the two cohorts. That is strong evidence that the findings are generalizable to a broad population of patients, and it sets an important example for future studies — including for other kinds of treatments — of how this kind of research should be done. But in the short term, we can see how this would make us more comfortable when a doctor decides to treat appendicitis with a course of antibiotics rather than rushing to the operating room, and it gives us another example of how the medical profession is improving its own practices to ensure that the subjects of its studies are representative of broad populations and free of biases. They are not there yet — far too many research studies still rely on conveniently accessible, unrepresentative populations of patients — but the problem is more broadly recognized today, and we can see visible progress in studies like this one.

Self-selection vs. Randomized Assignment of Treatment for Appendicitis


Kevin Schofield is a freelance writer and the founder of Seattle City Council Insight, a website providing independent news and analysis of the Seattle City Council and City Hall. He also co-hosts the “Seattle News, Views and Brews” podcast with Brian Callanan, and appears from time to time on Converge Media and KUOW’s Week in Review.

📸 Featured Image: Graphic by the Emerald team.

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