I've been getting a lot of questions recently about a new study that supposedly shows that the COVID-19 vaccines increase the risk for heart attacks. It took a while for me to figure out what some people were referring to, but it appears that this all started with an abstract presented at the AHA conference and included in the Circulation supplement that accompanied the conference. There are a few lessons to take away from this episode, the main one being why we should be wary of surrogate endpoints.
A few elements to the abstract should raise concerns for the clinician. First, the abstract has an "expression of concern" attached to it, which is rarely a sign that inspires confidence. Equally puzzling is how an abstract could have a single author and yet still say that the work was done by "our group." Also, at a mere 330 words, one can hardly subject this abstract to any type of significant critical scrutiny. In fact, one should probably be wary of putting too much emphasis on any piece of preliminary research presented at a conference because it would not be unusual, and would in fact be very likely, that the final results could differ significantly from what was presented.
But a more important issue with this abstract is the overreliance on surrogate markers. Generally speaking, one would prefer seeing studies done with hard clinical endpoints. In other words, if you want to study the risk for myocardial infarction, then your outcome should be the number of myocardial infarctions in a population. By the same token, if you want to test a new chemotherapeutic agent to see if it improves cancer-related mortality, then you must count the number of deaths in each arm of your study. But while these types of endpoints are the ideal, the downside to using these types of outcomes is the cost and length of follow-up that is often needed to generate enough data for any type of meaningful statistical analysis. Most studies need years' worth of follow-up to see enough major cardiovascular events and even then, many are underpowered to test what they actually set out to test.
The alternative is to use a surrogate marker. Rather than measuring cardiovascular events, you measure blood pressure, for example, and assume that if your test drug lowers a patient's blood pressure, then it probably reduces the risk for heart attack and stroke as well. By the same token, if your new chemotherapeutic agent lowers the levels of Ca-125, then you can infer that it probably helps reduce ovarian cancer mortality long-term.
It's worth pointing out that the use of surrogate endpoints in medical research is not inherently wrong. As a preliminary step, it can be a quicker and easier way to establish whether a new therapy has any merit. It can also be useful as a stepping stone to bolster grant applications and secure funding for larger, more definitive studies. But we should remember that surrogate markers rely on assumptions that sometimes do not hold true. High HDL cholesterol is associated with improved cardiovascular outcomes, and yet medications like niacin that raise HDL-C do not reduce the risk for heart disease. In a similar vein, CETP inhibitors should have worked in theory. They just didn't work in practice.
This is where the abstract presented at the AHA has its main weakness. This abstract did not actually look at myocardial infarction or any other cardiac endpoint. They looked at various inflammatory markers like interleukin-16 and hepatocyte growth factor. Setting aside for the moment how much value you want to put on the idea that cardiac disease is inflammatory in nature, we must by necessity acknowledge that this study didn't measure cardiac endpoints. It saw an increase in inflammatory markers post COVID-19 vaccination and then used those blood test results to infer an increase in cardiac risk.
A more critical person would have pointed out that of course you would see an increase in inflammatory markers post vaccination. The whole point of vaccination is to stimulate your immune system into making antibodies against COVID-19, and I would have been shocked if a patient's inflammatory markers didn't increase post vaccination. Since the researchers only measured these markers once post vaccination, we don't know if the levels eventually returned to normal afterward, which seems likely. Although it's worth pointing out that if these markers went up after vaccination, they probably would have increased after COVID-19 infection as well. But the real issue with this abstract is that it did not actually look at whether the vaccines caused more heart attacks. Other studies have looked at the risk of having a heart attack post vaccination and found no increased risk.
We must be careful about putting too much weight on preliminary research, especially before it's been peer reviewed and published in its final form. Although some may think they are doing a service to others by "getting the word out," we must be careful about the science communication equivalent of yelling "fire" in a crowded theater, lest we cause a panic when no fire actually exists.
Before we claim that the COVID-19 vaccines cause any problem, cardiac or otherwise, we should be sure about what we are saying. And if we are looking only at surrogate endpoints, we can't be.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Christopher Labos. Do the COVID-19 Vaccines Really Increase MI Risk? - Medscape - Dec 09, 2021.