title: Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of arterial thrombosis, but their effect on venous thrombotic events is less well established. The study aimed to assess the risk of symptomatic pulmonary embolism (PE) in patients using NSAIDs and to evaluate any effect of type, dose, and duration of therapy.
  
  
  METHODS
  A case-control study was conducted using the PHARMO Record Linkage System, a Dutch population-based registry. Cases were patients hospitalized with a primary diagnosis of PE and were matched to controls without a history of PE. To exclude confounding by indication, the effect of painkillers without known hemostatic effects was assessed.
  
  
  RESULTS
  The study population consisted of 4433 cases and 16,802 controls. After adjustment for surgery, trauma, and malignancy, current use of NSAIDs was associated with PE (odds ratio (OR) 2.39, 95% confidence interval (CI) 2.06-2.77). The risk was highest for traditional NSAIDs, and the overall risk for NSAIDs was highest in the first 30 days of exposure (OR 4.77, 95%CI 3.92-5.81), as compared with chronic (<1 year; OR 1.83, 95%CI 1.47-2.28) or long-term use (>1 year; OR 2.14, 95%CI 1.48-3.09). Use of acetaminophen and tramadol also increased the risk of PE (OR 1.74, 95%CI 1.42-2.14 and OR 4.07, 95%CI 2.86-5.75, respectively) with a similar time trend.
  
  
  CONCLUSIONS
  Use of NSAIDs is associated with an increased risk of symptomatic PE. This association may be partially explained by underlying medical conditions, as suggested by a similarly increased thrombotic risk in patients receiving acetaminophen and tramadol.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. s.rafi@amc.uva.nl
authors.forename: Sara
authors.initials: S
authors.lastname: Biere-Rafi
authors.forename: Marcello
authors.initials: M
authors.lastname: Di Nisio
authors.forename: Victor
authors.initials: V
authors.lastname: Gerdes
authors.forename: Ettore
authors.initials: E
authors.lastname: Porreca
authors.forename: Patrick
authors.initials: P
authors.lastname: Souverein
authors.forename: Anthonius
authors.initials: A
authors.lastname: Boer
authors.forename: Harry
authors.initials: H
authors.lastname: Büller
authors.forename: Pieter
authors.initials: P
authors.lastname: Kamphuisen
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D016208:Databases, Factual / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008498:Medical Record Linkage; D008875:Middle Aged; D009426:Netherlands; D011655:Pulmonary Embolism / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D013997:Time Factors; D014147:Tramadol / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D014147:Tramadol