During this respiratory virus season, several news headlines have suggested a potential slight increase in the risk of stroke caused by blood clots among patients 85 and older when they receive the COVID-19 and flu vaccines concurrently. In this edition of Diagnosing the Headlines, we checked in with Dr. Kabchi to understand if there is a potential risk and what the vaccine recommendations are for older patients. We also discuss the safety mechanisms at the Centers for Disease Control and Prevention (CDC) and the Federal Drug Administration (FDA) when reviewing the safety and incident reporting data on vaccines.

In January 2023, the FDA and the CDC identified data pointing to a possible increase in the risk of strokes caused by clots (ischemic strokes) in people aged 65 and older who received the bivalent Pfizer-BioNTech COVID-19 vaccine during the first 21 days after vaccination when compared with 22-42 days following vaccination. This was a very specific risk for a very specific vaccine in a very specific population. Further analysis of the available data did not validate this statistical signal; among other things, comparing the data with the unvaccinated population of similar age in a similar timeframe showed no difference in the risk of ischemic strokes between both groups.

Following this, the FDA and the Centers for Medicare and Medicaid Services (CMS) produced another study that several news outlets covered in October 2023. The study was published online without being peer-reviewed since the results are important to the public interest and publication in a medical journal through a peer-review process takes months, sometimes years. The study data was obtained from Medicare claims between Aug. 31, 2022, and Nov. 6, 2022, comparing beneficiaries aged 65 years and older receiving …

  • A Pfizer-BioNTech or Moderna COVID-19 bivalent vaccine,
  • A high-dose/adjuvant influenza vaccine or
  • Concomitant COVID-19 bivalent vaccine and influenza vaccine.

The primary analysis of the study did not find an elevated risk of any type of stroke after receiving COVID-19 bivalent vaccines. In the age subgroup analysis, adults 85 years and above had a 36 percent increase in the risk of ischemic strokes and a 28 percent increase in the risk of either ischemic stroke or transient ischemic attack (TIA) in the first 21 days after vaccination with the Pfizer-BioNTech vaccine. Among beneficiaries receiving a concomitant COVID-19 bivalent vaccine and a high-dose/adjuvanted influenza vaccine, a 20 percent increased risk was observed for ischemic strokes at days 22-42 with the Pfizer-BioNTech vaccine, and a 35 percent increase in the risk of TIA on days 1-21 with the Moderna vaccine.

Other less-reported results in this study are important to understanding these findings. For the similar Pfizer-BioNTech vaccine groups as above, the risk of only ischemic strokes in the first 21 days increased 14 percent in the 65-74 age group but decreased 16 percent in the 75-84 age group, and the risk of either ischemic stroke or TIA in the first 21 days increased 11 percent for the 65-74 age group and decreased 7 percent for the 75-84 age group. It is very unlikely that the risk of strokes in similar populations increases at a certain decade of life, decreases at the next and then increases to a higher degree during the following decade.

I suspect these results are a fluke, which is known to happen when an extensive subgroup analysis is done within a study. It highlights the possibility that the reported findings could be caused by chance despite being of statistical significance and the rigorousness of the study methodology. Furthermore, the FDA reported that other surveillance systems in the United States and other countries, as well as available studies, did not show an increase in the risk of strokes.

On the other hand, to place these numbers in perspective, we should consider the following:

  • Every year in the United States there are approximately 800,000 new cases of stroke, and more than 85 percent of these are ischemic.
  • The incidence of ischemic strokes in the US during the last quarter of 2022 was calculated to be around 1,500 per 1 million in the general population vs almost 6,000 in patients with influenza infection and almost 9,000 in patients with COVID-19 infection.
  • Through multiple studies, influenza and COVID-19 vaccination has been significantly associated with a decrease in the incidence of these infections as well as their severity and number of complications, including respiratory failure, strokes, heart attacks and death.

After reviewing FDA and CDC reports, what conclusions can be drawn about the risk of developing ischemic strokes to older adults who receive the vaccines concurrently?

Based on the available evidence, the concomitant administration of the mRNA COVID-19 and influenza vaccines is still safe. The FDA and CDC pointed to at least five studies, other surveillance systems and the review of their original statistical signal, which did not find an increased risk of strokes with the use of mRNA COVID-19 vaccines alone or in combination with the influenza vaccine.

This may be important for patients who live far from vaccination centers or have limited mobility or transportation and cannot arrange two separate vaccination visits. Nonetheless, it would be reasonable to receive these vaccines two weeks apart if there is still concern for any possible interaction or the confounding of side effects associated with the administration of either vaccine.

The Vaccine Safety Datalink (VSD) is a collaborative project between the CDC and integrated healthcare organizations and networks across the United States that monitors the safety of vaccines and conducts studies about rare and serious adverse events following immunization. It is one of many surveillance and monitoring systems in place. It collects data from doctors’ offices, urgent care visits, emergency department visits and hospital stays at 13 clinical sites throughout the United States. The VSD has published works on the safety of several vaccines of routine since its inception in 1990, including, among others, vaccines for human papillomavirus (HPV), seasonal flu, meningococcal disease and shingles. More recently, it published research papers establishing a small increased risk of developing Guillain-Barré syndrome and myocarditis/pericarditis after COVID-19 vaccination.

There are four main points I would consider:

  • First and most importantly, it remains safe for the general public to receive the COVID-19 and flu vaccines at the same time. If individuals are concerned about the findings, these articles can help initiate a conversation with their healthcare providers to make informed decisions that will benefit them and provide peace of mind. Receiving both vaccines two weeks apart is a reasonable strategy when feasible.
  • Any possible risks associated with receiving the COVID-19 and influenza vaccines, either alone or in combination, is greatly outweighed by the decrease in the risk of severity and possible complications if we acquired any of these infections.
  • There are innumerable factors to consider when balancing the risks and benefits of any treatment, and not all the essential information can be summarized in a headline. It is important that the news articles explain details of the studies and include interviews with medical professionals who put the study’s results in the right context.
  • When a medical recommendation is shared by several government and non-government organizations (in this case the CDC, FDA, CMS, hospitals and medical organizations), it reflects the best of the available evidence, and I am highly likely to give that same recommendation to my family, my friends and my patients.