People who received the newer Shingrix shingles vaccine had measurably less cardiovascular disease over the following seven years than those who got the older Zostavax shot, according to a study published Wednesday in Nature Medicine. The findings add to a growing body of evidence linking shingles vaccination to benefits beyond preventing the painful rash itself.
Researchers led by Fabiana Corsi-Zuelli and Maxime Taquet at the University of Oxford took advantage of a natural experiment: Shingrix replaced Zostavax as the recommended U.S. shingles vaccine in October 2017, so people vaccinated shortly before the switch received the older live vaccine while those vaccinated shortly after got the new recombinant one. Using electronic health records from the TriNetX network covering more than 60 U.S. health systems, the team matched roughly 36,000 Shingrix recipients age 60 and older against a similar-sized group who received Zostavax.
Over seven years, Shingrix recipients spent about 9% more time free of cardiovascular disease than the Zostavax group, translating to a 4% lower overall risk of a cardiovascular diagnosis. The gap was larger for specific conditions: a 10% reduction in ischemic heart disease, a 12% reduction in heart failure, and a 7% reduction in atrial fibrillation. Stroke risk was 12% lower among men who got Shingrix, though the difference was not statistically significant among women.
"Because we used a natural experiment created by the rapid switch between vaccines, our study addresses many of the biases of conventional cohort studies."
Fabiana Corsi-Zuelli, University of Oxford
An imperfect natural experiment
The design was intended to sidestep a common problem in vaccine research: people who choose to get vaccinated tend to be healthier to begin with, which can make a vaccine look more protective than it really is. By comparing two groups who were both willing to get vaccinated, just on either side of a policy switch, the researchers argue their comparison is less distorted by that healthy-vaccinee effect than typical observational studies. Even so, the study remains observational and cannot prove the vaccine itself caused the lower cardiovascular risk; shingles infection is known to trigger inflammation that can damage blood vessels, offering a plausible biological pathway, but confirming it requires a trial that randomly assigns vaccination. The TriNetX database also excludes people covered only by public insurance, which may limit how broadly the results apply.
"Although the benefits are relatively small on an individual basis, millions receive vaccination, meaning small benefits translate substantially at a population level."
Mark Russell, King's College London
One such trial, the Danish DAN ZOSTER study of roughly 162,000 people, is already underway and expected to produce initial results in 2027, according to Taquet, who separately noted that the same Oxford group has previously reported an association between Shingrix and lower dementia risk. In the meantime, the study's authors say the cardiovascular findings should not change current vaccination guidance, which already recommends Shingrix for adults 50 and older regardless of any heart benefit, but they add weight to arguments for expanding shingles vaccine access globally.
