title: Antihypertensive agents acting on the renin-angiotensin system and the risk of sepsis.
abstract: OBJECTIVE
  In response to safety concerns from two large randomized controlled trials, we investigated whether the use of telmisartan, an angiotensin receptor blocker (ARB), ARBs as a class and angiotensin-converting enzyme inhibitors (ACEIs) increase the risk of sepsis, sepsis-associated mortality and renal failure in hypertensive patients.
  
  
  METHODS
  We performed a nested case-control study from a retrospective cohort of adults with hypertension from the UK General Practice Research Database diagnosed between 1 January 2000 and 30 June 2009. All subjects hospitalized with sepsis during follow-up were matched for age, sex, practice and duration of follow-up with 10 control subjects. Exposure was defined as current use of antihypertensive drugs.
  
  
  RESULTS
  From the cohort of 550 436 hypertensive patients, 1965 were hospitalized with sepsis during follow-up (rate 6.9 per 10 000 per year), of whom 824 died and 346 developed acute renal failure within 30 days. Compared with use of β-blockers, calcium-channel blockers or diuretics, use of ARBs, including telmisartan, was not associated with an elevated risk of sepsis (relative risk 1.09; 95% confidence interval 0.83-1.43); but use ACEIs was (relative risk 1.65; 95% confidence interval 1.42-1.93). Users of ARBs, β-blockers, calcium-channel blockers or diuretics, but not users of ACEIs, had lower rates of hospitalization for sepsis compared with untreated hypertensive patients. Findings were similar for sepsis-related 30 day mortality and renal failure.
  
  
  CONCLUSIONS
  Hypertensive patients treated with ARBs, including telmisartan, do not appear to be at increased risk of sepsis or sepsis-related 30 day mortality or renal failure. On the contrary, users of ACEIs may have an increased risk.
authors.affiliation: Department of Critical Care, Jewish General Hospital, Montreal, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Dial
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Nessim
authors.forename: Abbas
authors.initials: A
authors.lastname: Kezouh
authors.forename: Jacques
authors.initials: J
authors.lastname: Benisty
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D012306:Risk; D018805:Sepsis / Q000453:epidemiology* / Q000209:etiology; D012720:Severity of Illness Index; D000077333:Telmisartan; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D000077333:Telmisartan
keywords: angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; hypertension; renal failure; sepsis; telmisartan