In an interview with Pharmacy Times®, Ali Dehghani, DO, doctor of internal medicine at Case Western Reserve University’s School of Medicine, explained the results of a study he presented at IDWeek 2025 in Atlanta, Georgia. The real-world analysis across 111 US health systems found that adults receiving recombinant zoster vaccine (RZV) had lower subsequent risks of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), dementia (especially vascular dementia), and mortality compared with those receiving pneumococcal conjugate vaccine (PCV). These associations persisted even after shingles occurred and after adjusting for health care engagement.
Pharmacy Times: For pharmacists counseling patients, what is the most important takeaway from these findings?
Ali Dehghani, DO: Key takeaway: shingles is not only a painful rash condition, but it also appears to function as a marker of longer-horizon vascular and neurocognitive risk, and RZV was associated with lower subsequent risk of MACE, dementia outcomes, and mortality compared with an active vaccine comparator. In our real-world analyses, we saw 2 clinically relevant patterns:
- After an incident of uncomplicated herpes zoster, risk elevation was not confined to the immediate post-rash period. Even starting follow-up after a 90-day landmark (to de-emphasize the known acute surge), herpes zoster was associated with higher hazards of MACE, VTE, dementia (including vascular dementia), and mortality over longer follow-up.
- Among adults who received RZV, outcomes were directionally favorable versus PCV across prespecified follow-up windows, with hazard ratios generally below 1.0 for MACE, VTE, dementia outcomes (especially vascular dementia patterns), and mortality.
Practical counseling implication for pharmacists: this reinforces the value of shingles vaccination as part of whole-person prevention. It is still first and foremost a shingles-prevention vaccine, but these data support discussing vaccination in the broader context of heart and brain health while being transparent that these are observational associations.
Pharmacy Times: The study compared outcomes in patients who received the shingles vaccine versus the pneumococcal vaccine. Why was this comparison important, and how should pharmacists interpret the differences in outcomes?
Dehghani: We used PCV as an active comparator for a specific reason: comparing vaccinated people to completely unvaccinated controls can inflate apparent benefits due to healthy-vaccinee bias and differences in health care engagement. PCV is:
- recommended in overlapping adult populations,
- delivered in similar preventive-care contexts,
- and does not have an obvious VZV-specific immunologic mechanism tied to shingles reactivation.
The RZV versus PCV comparison is a more stringent test than “vaccinated vs unvaccinated,” because both groups have demonstrated preventive-care behavior and vaccine access. In plain language: it helps ensure we are not simply measuring “people who get vaccines do better.” How pharmacists should interpret differences:
- These findings support an association between RZV receipt and lower downstream hazards versus PCV.
- They do not prove causality (residual confounding is still possible in any electronic health record [EHR]-based observational study).
- The fact that expected “positive control” outcomes behaved correctly (RZV recipients had lower subsequent zoster outcomes) supports internal coherence of exposure ascertainment and the analytic framing.
Pharmacy Times: How do these data change the way pharmacists should talk with patients about shingles as a broader cardiovascular and neurologic risk factor?
What Pharmacists Should Know
- Shingles vaccination may provide protective associations beyond rash prevention, including lower risk of major cardiovascular events, dementia, and death.
- Real-world data support early and ongoing patient counseling, emphasizing both shingles prevention and potential broader health benefits without overclaiming causality.
- Pharmacists can enhance uptake by identifying eligible patients, using reminders and structured counseling, and documenting vaccines to strengthen real-world evidence.
Dehghani: I would not frame this as “shingles causes heart attacks or dementia” in a deterministic way. But the data support a more nuanced and clinically useful message:
- Shingles may be a systemic signal, not purely a skin event. Even uncomplicated shingles was associated with a persistent “tail” of higher hazard for thrombo-ischemic outcomes and vascular cognitive diagnoses beyond the acute phase.
- This supports counseling that shingles prevention may matter not only for avoiding rash and postherpetic neuralgia, but also potentially for reducing downstream vascular and neurocognitive vulnerability.
Practical pharmacist messaging:
- For zoster-naïve patients: “Shingles vaccination helps prevent shingles, and in large real-world datasets it has also been linked with lower rates of major cardiovascular events and dementia diagnoses compared with another common adult vaccine.”
- For patients who already had shingles: “Your shingles episode may be a cue to optimize cardiovascular risk factors and preventive care. Vaccination is still important to reduce recurrence, and, in our analyses, the association with better downstream outcomes was not confined to people vaccinated only before shingles.”
That last point is important: in sensitivity analyses, the direction of protection was similar whether vaccination occurred before or after the shingles episode, which argues against a simplistic interpretation that the only pathway is “prevent the first rash, therefore prevent everything else.” It also strengthens the idea that shingles vaccination may be linked to trajectory modification, while still acknowledging confounding remains possible.
Pharmacy Times: Because this was a large real-world analysis across more than 100 US health systems, how confident can pharmacists be applying these findings in everyday clinical and community pharmacy settings?
Dehghani: There are reasons for both confidence and appropriate restraint.
Reasons for confidence/applicability:
- The dataset spans a large, diverse network (111 US health systems), which supports generalizability to “everyday” patients rather than a narrowly selected trial population.
- We used propensity score matching and prespecified delayed-entry (landmark) designs to reduce immortal time bias, reverse causation, and acute-phase confounding.
- Findings were directionally consistent across prespecified windows and robustness checks.
Reasons for caution:
- This is still observational EHR research, so residual confounding is possible (frailty, socioeconomic factors, health behaviors, and unmeasured care patterns can remain imperfectly captured).
- Vaccines given outside a health system may be under-recorded, and outcome coding (especially vascular dementia) can be imperfect.
- Hazard ratios describe relative differences; absolute differences are clinically meaningful but modest and should be communicated carefully.
Bottom line for pharmacists: these results are strong enough to reinforce vaccination counseling and preventive-care messaging, but not to justify overpromising or making causal claims beyond the data.
Pharmacy Times: Given ongoing vaccine hesitancy, particularly among older adults, how can pharmacists use these findings to address concerns and reinforce the value of shingles vaccination beyond rash prevention?
Dehghani: Pharmacists are uniquely positioned because they can translate population-level data into a patient’s personal priorities. A practical approach:
- Start with what is already firmly established. RZV is highly effective at preventing shingles and postherpetic neuralgia, and it has extensive post-licensure safety monitoring.
- Add a “why it matters to you” layer. Many older adults fear stroke, heart attack, and loss of independence more than they fear a rash. These findings allow a clinically responsible message such as:
“In a large real-world analysis, people who received the shingles vaccine had lower rates of major cardiovascular events and dementia diagnoses compared with people receiving another routine adult vaccine. That doesn’t prove cause and effect, but it strengthens the preventive value of getting vaccinated.”
- Normalize short-term side effects and plan for them. Acknowledge reactogenicity (arm soreness, fatigue, myalgias) and suggest practical planning (schedule around important events; hydration; OTC symptom relief if appropriate).
- Emphasize that it’s still beneficial even if they had shingles. This is often overlooked. You can incorporate your sensitivity-analysis point in a patient-friendly way:
“Even among people who later had shingles, the vaccine group still showed better downstream outcomes in our analyses. So vaccination is not ‘too late’ just because someone already had an episode.”
Pharmacy Times: What additional research is needed to better define the cardioprotective and neuroprotective effects of shingles vaccination, and how can pharmacists help support uptake while the evidence continues to evolve?
Dehghani: What we still need:
- Stronger causal designs (for example, target-trial emulation with richer confounder control, negative control outcomes, and linkage to immunization registries).
- Mechanistic studies that connect vaccination to biologic intermediates (vascular inflammation, endothelial activation, coagulation markers, and markers of subclinical reactivation).
- Analyses of dose completion, timing, and high-risk subgroups (advanced age, diabetes, ASCVD, immunocompromised populations).
- Work to clarify whether observed cognitive associations track most closely with vascular pathways (as suggested by vascular dementia signals) versus neurodegenerative pathways.
How pharmacists can support uptake right now:
- Systematically identify eligible patients (immunization record reviews, medication triggers like immunosuppressants, age-based prompts).
- Implement reminder/recall systems and strong workflows to ensure second-dose completion.
- Use brief, structured counseling that links vaccination to patient goals (independence, stroke prevention, brain health) while being transparent about observational limits.
- Document vaccines accurately (including state registries where applicable) to improve real-world data quality.
- Continue pharmacovigilance and safety reporting, which strengthens public confidence over time.