title: Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies.
abstract: OBJECTIVE
  The association between hemorrhagic stroke and use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not well established. We conducted a systematic review and meta-analysis of observation studies to further characterize this possible association.
  
  
  METHODS
  Case-control and cohort studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of hemorrhagic stroke among NSAIDs users versus nonusers were systematically searched. Point estimates from each study were extracted. Pooled risk ratios (RR) and 95% confidence intervals (CI) for all NSAIDs and individual NSAIDs were calculated using random-effect, generic inverse variance method.
  
  
  RESULTS
  Ten studies were identified and included in our data analysis. As a single group, NSAIDs use was associated with a small but insignificant risk of hemorrhagic stroke with the pooled RR of 1.09 (95% CI, 0.98-1.22). Individual NSAIDs analysis revealed a significantly increased risk among diclofenac and meloxicam users (RR 1.27; 95% CI, 1.02-1.59 and RR 1.27; 95% CI, 1.08-1.50, respectively). The risk estimate for rofecoxib users was higher, but statistically nonsignificant (RR 1.35; 95% CI, 0.88-2.06).
  
  
  CONCLUSIONS
  Overall, the use of NSAIDs is not associated with an increased risk of hemorrhagic stroke, although this risk was modestly significantly elevated in diclofenac and meloxicam users.
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN (P.U., E.L.M.); Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (P.U.); Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN (E.L.M.); and Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN (C.T.). Ungprasert.Patompong@mayo.edu.
authors.forename: Patompong
authors.initials: P
authors.lastname: Ungprasert
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN (P.U., E.L.M.); Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (P.U.); Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN (E.L.M.); and Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN (C.T.).
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
authors.affiliation: From the Division of Rheumatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN (P.U., E.L.M.); Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (P.U.); Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN (E.L.M.); and Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN (C.T.).
authors.forename: Charat
authors.initials: C
authors.lastname: Thongprayoon
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000150:complications / Q000453:epidemiology*; D004008:Diclofenac / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D015994:Incidence; D007213:Indomethacin / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use; D000077239:Meloxicam; D009288:Naproxen / Q000627:therapeutic use; D064887:Observational Studies as Topic; D016017:Odds Ratio; D010894:Piroxicam / Q000627:therapeutic use; D016016:Proportional Hazards Models; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology; D013450:Sulfones / Q000627:therapeutic use; D013843:Thiazines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007783:Lactones; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; C116926:rofecoxib; D010894:Piroxicam; D004008:Diclofenac; D009288:Naproxen; D000068579:Celecoxib; D000077239:Meloxicam; D007052:Ibuprofen; D007213:Indomethacin
keywords: cyclooxygenase; hemorrhagic stroke; meta-analysis; nonsteroidal anti-inflammatory drugs; stroke