Damian McNamara

LOS ANGELES — Prevention of shingles with the Zoster Vaccine Live (Zostavax, Merck) may reduce the risk of subsequent stroke among older adults as well, the first study to examine this association suggests.

Shingles vaccination was linked to a 20% decrease in stroke risk in people under 80 years of age in the large Medicare cohort study. Older participants showed a 10% reduced risk, according to data released in advance of formal presentation at this week’s International Stroke Conference (ISC) 2020 in Los Angeles. Reductions were seen for both ischemic and hemorrhagic events.

“Our findings might encourage people age 50 or older to get vaccinated against shingles and to prevent shingles-associated stroke risk,” Quanhe Yang, PhD, lead study author and senior scientist at the Centers for Disease Control and Prevention (CDC) in Atlanta, told Medscape Medical News.

Yang and colleagues evaluated the only shingles vaccine available at the time of the study, Zoster Vaccine Live, sold under the brand name Zostavax. However, the CDC now calls an adjuvanted, non-live recombinant vaccine (Shingrix, GlaxoSmithKline) the preferred shingles vaccine for healthy adults aged 50 and older. Shingrix was approved in 2017. Zostavax, approved in 2006, can still be used in healthy adults over age 60, the agency states.

A reduction in inflammation from Zoster Vaccine Live may be the mechanism by which stroke risk is reduced, Yang said. The newer vaccine, which the CDC notes is more than 90% effective, might provide even greater protection against stroke, although more research is needed, he added.

Interestingly, prior research suggests that once a person develops shingles, it may be too late. Yang and colleagues showed vaccination or antiviral treatment after a shingles episode was not effective at reducing stroke risk in research presented at ISC 2019, as previously reported by Medscape Medical News.

Shingles can present as a painful reactivation of chickenpox, also known as the varicella-zoster virus. Shingles is also common; Yang estimated 1 in 3 people who had chickenpox will develop the condition at some point in their lifetime. In addition, researchers have linked shingles to an elevated risk of stroke.

To assess the vaccine’s protective effect on stroke, Yang and colleagues reviewed health records for 1.38 million Medicare recipients. All participants were aged 66 years or older, had no history of stroke at baseline, and received the Zoster Vaccine Live between 2008 and 2016.

The investigators compared the stroke rate in this vaccinated group to the rate in a matched control group of the same number of Medicare fee-for-service beneficiaries who did not receive the vaccination. They adjusted their analysis for age, gender, race, medications, and comorbidities.

The overall decrease of 16% in stroke risk associated with vaccination included a 12% drop in hemorrhagic stroke and 18% decrease in ischemic stroke over a median follow-up of 3.9 years follow-up (interquartile range 2.7-5.4).

The adjusted hazard ratios comparing the vaccinated to control groups were 0.84 (95% confidence interval [CI], 0.83 – 0.85) for all stroke; 0.82 (95% CI, 0.81 – 0.83) for acute ischemic stroke; and 0.88 (95% CI, 0.84 – 0.91) for hemorrhagic stroke.

The vaccinated group experienced 42,267 stroke events during that time. This rate included 33,510 acute ischemic strokes and 4318 hemorrhagic strokes. At the same time, 48,139 strokes occurred in the control group. The breakdown included 39,334 ischemic and 4713 hemorrhagic events.

“Approximately 1 million people in the United States get shingles each year, yet there is a vaccine to help prevent it,” Yang stated in a news release. “Our study results may encourage people ages 50 and older to follow the recommendation and get vaccinated against shingles. You are reducing the risk of shingles, and at the same time you may be reducing your risk of stroke.”

“Further studies are needed to confirm our findings of association between Zostavax vaccine and risk of stroke,” Yang said.

Because the CDC Advisory Committee on Immunization Practices (ACIP) only recommended Shingrix vaccine for healthy adults 50 years and older in 2017, there was insufficient data in Medicare to study the association between that vaccine and risk of stroke at the time of the current study.

“However, two doses of Shingrix are more than 90% effective at preventing shingles and postherpetic neuralgia, and higher than that of Zostavax,” Yang said.

“Very Intriguing” Research
“This is a very interesting study,” Ralph L. Sacco, MD, past president of the American Heart Association, said in a video commentary released last week in advance of the conference. It was a very large sample, he noted, and those who had the vaccine over age 60 were protected with a lower risk for both ischemic and hemorrhagic stroke.

“So it is very intriguing,” added Sacco, chairman of the department of neurology at the University of Miami Leonard Miller School of Medicine in Florida.

“We know things like shingles can increase inflammation and increase the risk of stroke,” Sacco said, “but this is the first time in a very large Medicare database that it was shown that those who had the vaccine had a lower risk of stroke.”

The US Centers for Disease Control and Prevention funded this study. Yang and Sacco have disclosed no relevant financial relationships.

International Stroke Conference (ISC) 2020. Abstract TP493. To be presented February 20, 2020.