Table 1.
Study Characteristics and Main Results
| Author (y) | Setting | Study Design and Period | Population | Exposure(s) | Outcome(s) | Effect of HZ on Stroke, Adjusted Effect Measure (95% CI) | Effect of HZ on MI, Adjusted Effect Measure (95% CI) |
|---|---|---|---|---|---|---|---|
| Minassian ( 2015) [12] | United States, Medicare claims data | Self-controlled case series, 2006–2011 | Patients (≥65 y) with HZ and stroke/TIA Excluded if had HZ or vascular events preentry or SAH ever or encephalitis in 12 mo poststroke | HZ episode: I CD-9 code with antiviral 7 d before or after HZ Exposed period to 12 mo after HZ (wk 1, wk 2–4, 5–12, 13–26, 27–52) | Primary: (1) ischaemic stroke, (2) MI Secondary: hemorrhagic stroke (ICD-9 codes) |
wk 1: IR 2.37 (2.17–2.59) wk 2–4: IR 1.55 (1.46–1.66) wk 5–12: IR 1.17 (1.11–1.22) wk 13–26: IR 1.03 (0.99–1.07) wk 27–52: IR 1.00 (0.96–1.03) |
wk 1: IR 1.68 (1.47–1.92) wk 2–4: IR 1.25 (1.14–1.37) wk 5–12: IR 1.07 (1.00–1.14) wk 13–26: IR 1.02 (0.96–1.07) wk 27–52: IR 1.02 (0.98–1.07) |
| Langan (2014) [13] | UK, primary care records from CPRD linked to secondary care records from HES | Self-controlled case series, 1987–2012 | Adults (≥18 y) with 1st ever HZ and stroke Exclusions: incident TIA, SAH, encephalitis in 12 mo after stroke | First ever HZ: Read and ICD-10 codes Exposed period from day after HZ to 12 mo (wk 1–4, 5–12, 13–26, 27–52) | Primary: arterial stroke Secondary: cerebral infarction, hemorrhagic, or unspecified stroke (Read and ICD-10 codes) |
wk 1–4: IR 1.63 (1.32–2.02) wk 5–12: IR 1.42 (1.21–1.68) wk 13–26: IR 1.23 (1.07–1.42) wk 27–52: IR 0.99 (0.88–1.12) |
… |
| Schink (2016) [14] | Germany, health claims from 4 insurance providers, hospitalizations, and outpatients data | Self-controlled case series, 2004–2011 | Patients (any age) with HZ and stroke, ≥12 mo follow-up, no history of HZ or stroke in 12 mo before cohort entry | First or recurrent HZ: ICD-10 code or antiviral with HZ outpatient diagnosis Exposed period to 12 mo after HZ (0–2 wk, 3–4 wk, 2–3 mo, 4–6 mo, 7–12 mo) | Primary: first stroke Secondary: ischaemic, hemorrhagic, unspecified type of stroke or TIA (ICD- 10 codes for main discharge diagnosis in hospital record) |
<2 wk: IRR 1.30 (1.00–1.68) wk 3–4: IRR 1.52 (1.20–1.91) mo2–3: IRR 1.24 (1.08–1.42) mo 4–6: IRR 1.09 (0.97–1.24) mo 7–12: IRR 0.96 (0.87–1.06) |
… |
| Sreenivasan (2013) [16] | Denmark, routinely collected civil registration data and health registers | Cohort, 1995–2008 | All Danish adults (≥18 y) alive during study period Persons with outcome before start of follow-up excluded | HZ treated with antivirals: acyclovir prescription (800 mg in packages of 35 tablets) | Stroke or TIA, composite outcome (ICD-8 and 10 codes from National Patient Registry) | <14 d since HZ: IRR 2.27 (1.83–2.82) 14 d–1 y: IRR 1.17 (1.09–1.24) >1 y: IRR 1.05 (1.02–1.09) |
… |
| Sundström (2015) [17] | Sweden, routinely collected health data from 1 county | Cohort, 2008–2010 | All incident cases of HZ occurring within the study period in this region No age restriction |
HZ from ICD- 10 diagnosis codes with no history of HZ in the previous year | Stroke (ICD-10 diagnosis within 1 y of HZ) | IRR 1.34 (1.12–1.62) | … |
| Yawn (2016) [18] |
United States, medical records from Olmsted County | Cohort, 1986–2011 | All adults (≥50 y) with HZ matched by sex and age ± 1 y to adults without HZ Patients with history of stroke excluded |
First or recurrent HZ: ICD-9 code and HZ clinical symptoms in medical records | (1) Stroke, (2) MI (diagnostic codes from hospital admissions or death records, <30 days before cohort entry or until cohort exit) | 3 mo: OR 1.53 (1.01–2.33) 6 mo: OR 1.28 (0.91–1.80) 1 y: OR 1.04 (0.79–1.36) 3 y: OR 1.02 (0.86–1.22) |
3 mo: OR 1.68 (1.03–2.75) 6 mo: OR 1.44 (0.97–2.15) 1 y: OR 1.33 (0.99–1.80) 3 y: OR 1.17 (0.97–1.41) |
| Calabrese (2017) [19] | United States, Medicare claims data | Cohort, 2006–2013 | Adults (≥65 y) with HZ, ≥12 mo follow-up at entry, inflammatory disease (AS/ IBD/ psoriasis/ psoriatic arthritis/ RA), no prior stroke or antiviral therapy | Inpatient or outpatient diagnosis of HZ: ICD-9 diagnosis code and no same day code for zoster vaccine | Primary: any stroke (ICD-9 diagnosis code in any position on hospital claim) Secondary: ischaemic stroke |
0–90 days: IRR 1.36 (1.10–1.68) 91–365 days: IRR 1.18 (1.00–1.40) Baseline: 366–730 days |
… |
| Kang (2009) [20] | Taiwan, National Health Research Institute claims database | Cohort, 1997–2001 | Adults (≥18 y) with HZ and no history of stroke matched by age/sex to 3 patients with no history of HZ or stroke before 2001 | Treatment for HZ in ambulatory care: ICD-9 codes | Primary: stroke, any Secondary: ischaemic or hemorrhagic stroke (ICD-9 codes) |
Risk of stroke during the 1-y follow-up period: HR 1.31 (1.06–1.60) | … |
| Lin (2010) [21] | Taiwan, National Health Research Institute claims database | Cohort, 2003–2005 | Immunocompetent adults (≥18 y) with HZO, matched by age/sex to 3 patients without HZO Those with stroke prior to entry excluded | Ambulatory care for HZO: ICD-9 code (Patients with HZO in previous year excluded) | Stroke, definition unspecified (likely ICD-9 codes) | HR 4.52 (2.45–8.33) | … |
| Breuer (2014) [22] | UK, primary care records from THIN | Cohort, 2002–2010 | Adults (≥18 y) with HZ; age (±2 y), sex and practice matched adults with no HZ | Nonrecurrent HZ: Read codes | Primary: (1) first incident stroke or TIA, (2) MI Secondary: stroke type (Read codes) |
Stroke: HR 1.02 (0.98–1.07) TIA: HR 1.15 (1.09–1.21) |
MI: HR 1.10 (1.05–1.16) |
| Kwon (2016) [23] | Korea, 1 million sample of national health insurance database | Cohort, 2003–2013 | All patients (>18 y) in database: those with HZ or stroke during 1st year of observation period excluded | First HZ in observation period: ICD-10 codes | First stroke or TIA (ICD-10 codes) | 18–30 y: HR 1.52 (1.26–1.83) 30–40 y: HR 1.34 (1.19–1.51) 40–50 y: HR 1.19 (1.12–1.29) 50–60 y: HR 1.12 (1.06–1.19) 60–70 y: HR 1.14 (1.08–1.20) >70 y: HR 1.14 (1.06–1.23) |
… |
| Wang (2014) [24] | Taiwan, National Health Research Institute claims database | Cohort, 1999–2010 | Patients (age not stated) with HZ and no history of acute coronary syndrome matched by age, sex, and year to 4 patients without HZ | Incident HZ: ICD-9 code | Incident ACS (ICD-9 codes) | … | HR 1.15 (1.07–1.24) |
Abbreviations: ACS, acute coronary syndrome; AS, ankylosing spondylitis; CI, confidence interval; CPRD, Clinical Practice Research Datalink; HES, Hospital Episode Statistics; HR, hazard ratio; HZ, herpes zoster; HZO, herpes zoster ophthalmicus; IBD, inflammatory bowel disease; ICD, International Classification of Diseases; IR, incidence ratio; IRR, incidence rate ratio; MI, myocardial infarction; OR, odds ratio; RA, rheumatoid arthritis; SAH, subarachnoid hemorrhage; THIN, The Health Improvement Network; TIA, transient ischaemic attack.