title: Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study.
abstract: OBJECTIVE
  To assess whether a double therapy combination consisting of diuretics, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers with addition of non-steroidal anti-inflammatory drugs (NSAIDs) and the triple therapy combination of two of the aforementioned antihypertensive drugs to which NSAIDs are added are associated with an increased risk of acute kidney injury.
  
  
  METHODS
  Retrospective cohort study using nested case-control analysis.
  
  
  METHODS
  General practices contributing data to the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database.
  
  
  METHODS
  A cohort of 487,372 users of antihypertensive drugs.
  
  
  METHODS
  Rate ratios with 95% confidence intervals of acute kidney injury associated with current use of double and triple therapy combinations of antihypertensive drugs with NSAIDs.
  
  
  RESULTS
  During a mean follow-up of 5.9 (SD 3.4) years, 2215 cases of acute kidney injury were identified (incidence rate 7/10,000 person years). Overall, current use of a double therapy combination containing either diuretics or angiotensin converting enzyme inhibitors or angiotensin receptor blockers with NSAIDs was not associated with an increased rate of acute kidney injury. In contrast, current use of a triple therapy combination was associated with an increased rate of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). In secondary analyses, the highest risk was observed in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46).
  
  
  CONCLUSIONS
  A triple therapy combination consisting of diuretics with angiotensin converting enzyme inhibitors or angiotensin receptor blockers and NSAIDs was associated with an increased risk of acute kidney injury. The risk was greatest at the start of treatment. Although antihypertensive drugs have cardiovascular benefits, vigilance may be warranted when they are used concurrently with NSAIDs.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine Montreal, Quebec H3T 1E2, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Nessim
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D016022:Case-Control Studies; D016001:Confidence Intervals; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D060735:Pharmacovigilance; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D004232:Diuretics