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Statins increased risk for herpes zoster in older adults
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Older adults who use statins had a small but significant increased risk for herpes zoster, researchers from St. Michael’s Hospital in Toronto have found.
“Given the widespread use of statins and the substantial morbidity associated with herpes zoster, further research is needed to clarify the exact mechanisms through which statins promote varicella-zoster virus reactivation and whether our findings are generalizable to younger patients receiving these drugs,” the researchers wrote in Clinical Infectious Diseases.
The researchers used administrative health care data to conduct a population-based retrospective cohort study that included all residents in Ontario who were aged at least 66 years from April 1, 1997, to March 31, 2010. They determined the statin exposure through prescription records and also obtained data on physician services, including hospitalization and ED visits. The individuals were divided into two groups: 494,651 who received a prescription for a statin and an equal number who had not. Collectively, the entire cohort included 1,553,288 person-years of follow-up.
There were 19,143 instances of herpes zoster in the cohort. Those who used statins had a higher rate: 13.25 per 1,000 person-years compared with 11.71 per 1,000 person-years for those who did not use statins (HR=1.13; 95% CI, 1.1-1.17). When the analysis was contained to only patients who filled more than one statin for prescription, these results were unchanged. Among the statin users, there was a higher risk for herpes zoster in a subgroup of patients with diabetes (HR=1.18; 95% CI, 1.09-1.27).
There was no difference in herpes zoster risk according to the dose of statins in a dose-response analysis. When compared with low doses of the drugs, a moderate dose had an HR of 1.05 (95% CI, 1-1.1) and a high dose had an HR of 1.03 (95% CI, 0.9-1.19). However, fewer than one in 10 patients had a dose increase since baseline.
“Our study provides the first empirical evidence of an association between statins and herpes zoster and suggests that the widespread use of these drugs may be an important factor accounting for the increased incidence of this disease among otherwise immunocompetent older individuals,” the researchers wrote. “For patients in whom statin therapy is required, our findings suggest that provision of the herpes zoster vaccine should be considered.”
Disclosure: One researcher has served on the advisory boards of and received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Novo Nordisk and Pfizer.
Perspective
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William Schaffner, MD
The results of this study came as a small surprise to me as I had not thought about statins in relation to herpes zoster. The authors used several large comprehensive administrative healthcare databases that included all residents of Ontario, Canada, aged 66 years and older to study the occurrence of herpes zoster from April 1, 1997 through March 31, 2010. The authors compared the frequency of zoster in persons who were treated with one or more of the seven statins available in Ontario during the 13-year study interval with matched, untreated controls. In short, treatment with statins was associated with a small increased risk of zoster. The findings were affirmed by a subgroup analysis among patients with diabetes showing a similarly small increased risk of zoster among statin users. As a further validation, the authors showed that statin users were not at increased risk of having a knee arthroplasty procedure.
This looks like solid work with an intriguing result that has biologic plausibility. Although statins are prescribed to reduce lipid levels, it is less well recognized that they also have several immunomodulating effects, providing an explanation for why they may be enhancing the reactivation of a latent viral infection.
The only aspect of the study that bothers me is that the use of zoster vaccine in the population was not taken into account. I do not know when zoster vaccine was licensed in Ontario; it was licensed in the United States in 2006, about two-thirds of the way into this study.
I doubt whether this result will become yet another consideration adding to the recent brouhaha over the appropriate use of statins, but it does remind us about the importance of providing zoster vaccine to all our patients aged 60 years and older. The latest data from the CDC indicate that only about 20% of persons aged 60 years and older have received zoster vaccine, so there’s plenty of work yet to do. I know that it is cumbersome under Medicare to provide this vaccine because it has been assigned to Part D. Our internists here at Vanderbilt refer their patients to our pharmacy where the pharmacists give the vaccine.
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