The study is the first global systematic literature review and meta-analysis to comprehensively assess the evidence regarding an association between herpes zoster vaccination and cardiovascular events.
The results are being presented at the 2025 European Society of Cardiology Congress in Madrid, Spain. Study author, Dr Charles Williams, Global Associate Medical Director, Global Medical Affairs – Vaccines at GSK, said: “We looked at the currently available evidence, and found that in this analysis, vaccination against herpes zoster was associated with a lower risk of cardiovascular events, such as heart attacks or strokes. Further research studies are now needed to find out whether this association can be attributed to an effect of herpes zoster vaccination,” Dr Williams continued.
The study found that herpes zoster vaccination, with either the recombinant herpes zoster vaccine (RZV) or the live attenuated zoster vaccine (ZVL), was associated with a statistically significant lower risk of stroke and heart attack compared to no herpes zoster vaccination, in both adults ≥18 years, and adults ≥50 years. The research found that vaccination against shingles, with either RZV or ZVL, was associated with an 18% and 16% reduction in risk of cardiovascular events in adults 18 and 50 years or older, respectively. In studies that reported on cardiovascular event absolute risk, the absolute rate difference ranged from 1.2 to 2.2 fewer events per 1,000 person-years.
The global systematic literature review was conducted using three scientific literature databases, and a meta-analysis was conducted of phase 3 randomized controlled trials and observational studies assessing the effect of herpes zoster vaccination on cardiovascular events. The meta-analysis inclusion criteria followed Cochrane guidelines (1).
19 studies were included in the review; eight observational studies and one randomized controlled trial (a pooled safety analysis of two Phase 3 randomized trials; not designed or powered to evaluate the effects of herpes zoster vaccination against cardiovascular events), met the meta-analysis inclusion criteria for herpes zoster vaccination effectiveness on cardiovascular events. Across all nine studies, 53.3% of participants were male. Seven studies reported mean ages from 53.6 years to 74.0 years.
“While our findings are encouraging, there are some limitations to the available data that we studied,” Dr Williams explained. “Almost all the evidence came from observational studies, which are prone to bias and shouldn’t be used to infer causality. All the studies used in the meta-analysis aimed primarily to investigate the use of herpes zoster vaccine to prevent shingles in the general population, which may limit the ability to generalise this research to people with a higher risk of cardiovascular events. This demonstrates the need for more research in this area.”
Previous research has shown a transient increased risk of stroke and heart attack following shingles (2), but it is not confirmed whether vaccination against the disease could reduce cardiovascular risk.
Shingles, also known as herpes zoster, is caused by a reactivation of the varicella-zoster virus (VZV), the same virus that causes chickenpox. After primary infection, the virus remains dormant within the nervous system and reactivates, causing shingles in around one in three individuals during their lifetime (3–5). VZV can also invade large and small blood vessels in the head, which can lead to inflammation and vascular remodelling. It is thought that this may lead to complications such as stroke, following the reactivation of VZV .
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