No Stroke Risk Reduction Seen With Post-Onset Shingles Rx

Patrice Wendling

February 01, 2019

Receiving a herpes zoster (HZ) vaccination, antiviral therapy, or both after an episode of shingles does not reduce the increased risk for acute ischemic stroke associated with the disease, researchers say.

Quanhe Yang

"Surprisingly, we expected to see some modification if you have vaccination or treatment, and tried our best to look at this in different ways, but there was no difference," study author Quanhe Yang, PhD, senior scientist, division of heart disease and stroke prevention, Centers for Disease Control and Prevention, told | Medscape Cardiology.

HZ affects about one million Americans each year and is associated with an increased risk for stroke, particularly shortly after infection. A few studies have examined risk modification by HZ vaccination status and antiviral treatment, but sample sizes have been small, outcome definitions varied, and results mixed, he explained.

Yang and colleagues conducted a self-controlled case series study of 35,186 US Medicare fee-for-service beneficiaries (≥66 years) diagnosed with HZ during 2008 and 2014 and then diagnosed with acute ischemic stroke in the year after the index HZ.

Patients were classified into four groups on the basis of HZ treatment status (no treatment, vaccination with Zostavax [Merck], antiviral treatment only, both vaccination and antivirals) and incident rate ratios (IRRs) calculated for four risk periods (0–14, 15–30, 31–90, and 91–180 days aftet HZ). Patients' average age was 80 to 81 years.

Acute ischemic stroke risk spiked 61% within 14 days of shingles onset (IRR, 1.61; 95% CI, 1.51 - 1.70) and remained elevated at 1 month (IRR, 1.35; 95% CI, 1.27 - 1.44), before declining at 31 to 90 days (IRR, 1.16; 95% CI, 1.12 - 1.20) and 91 to 180 days (IRR, 1.05; 95% CI, 1.02 - 1.08).

This pattern was consistent in all four patient groups and across groups based on age, sex, and race/ethnicity, according to data released January 30 in advance of its formal presentation at next week's International Stroke Conference (ISC) 2019 in Honolulu.

"This is a selected Medicare population but I think we can say these results are generalizable to the general population [aged] 65-plus," Yang said. "But for younger age groups or immunocompromised patients, we don't have the evidence to say if it can be generalized."

A recent meta-analysis of 48 studies also reported short-term increased stroke risk with herpes viruses, but also found evidence suggesting risk was greater among ophthalmic zoster patients, younger age groups, and patients not prescribed antivirals. The authors posited that herpes viruses might increase stroke risk by inducing acute inflammation, which can lead to endothelial dysfunction, disruption of atheromatous plaques, and hypercoagulability, or might directly invade cerebral arteries, producing vasculopathy.

"The one thing that strikes you is that stroke risk increases almost at onset," Daniel Lackland, MD, professor of neurology and epidemiology, Medical University of South Carolina, Charleston, told | Medscape Cardiology.

Although this finding has been reported in several studies, the diagnosis of shingles may have varied, he said. Most people use skin lesions as part of the diagnosis, but there can be times when those are absent. Pain is common at the time of diagnosis but might not indicate when the underlying pathophysiology for stroke began.

"So there is the possibility that treatment does absolutely nothing, but it could also be that when the treatment is initiated, the risk is already developed," said Lackland, who was not involved in the study.

Two caveats to the current study are that Medicare data might have missed patients who did not seek care for HZ but could have derived a stroke benefit, and that the efficacy of Zostavax declines over time (median, 23 months), Yang said.

The new recombinant and adjuvanted herpes zoster vaccine (Shingrix, GlaxoSmithKline) was approved in 2017 for adults 50 years and older, whereas Zostavax, the live, attenuated virus version, is recommended for adults 60 years and older. Early surveillance data from the first 8 months of Shingrix use are consistent with the safety profile reported in prelicensure clinical trials, according to a study reported this week.

"The good news is with the new Shingrix, the efficacy is over 90% and, although there isn't a lot of follow-up, it looks like over 3 or 4 years it declines only about 2% or 3% points," Yang said. "We're looking forward to seeing what the new vaccine does preventing the shingles, cardiovascular disease, and stroke."

In the meantime, eligible patients should continue to be vaccinated, he said. "Our findings suggest the importance of following recommended HZ vaccination in prevention of HZ."

Although it's possible that some antivaxxers will interpret the lack of stroke benefit as reason to avoid HZ vaccination, that would be entirely the wrong message, Lackland said.

"We certainly know there is an association between shingles and stroke, and I feel it's good even with cardiovascular disease, and certainly shingles is not something that's comfortable, that you just walk away from in a day," Lackland said. "So those two together would tell you you'd want to lean on the side of treating shingles, which is the correct thing."

"This study adds to the literature but I don't think we've answered the question," he added. "Further studies need to be looked at to determine the benefit of treating with regard to reducing the risk of stroke after shingles. And some of that refined study probably needs to look at when is the onset, when do you initiate treatment, and when is the onset of what some people would refer to as the stroke-development risk."

The authors and Lackland report no relevant financial conflicts of interest.

International Stroke Conference 2019. Abstract 39. To be presented February 6, 2019.

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