title: The effect of losartan versus atenolol on cardiovascular morbidity and mortality in patients with hypertension taking aspirin: the Losartan Intervention for Endpoint Reduction in hypertension (LIFE) study.
abstract: OBJECTIVE
  We conducted a subgroup analysis in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study to determine whether aspirin interacted with the properties of losartan, an angiotensin-II receptor antagonist.
  
  
  BACKGROUND
  Negative interactions between angiotensin-converting enzyme inhibitors and aspirin have been reported. There are no data reported from clinical trials about possible interactions between angiotensin-II receptor antagonists and aspirin.
  
  
  METHODS
  The LIFE study assigned 9,193 patients with hypertension and left ventricular hypertrophy (LVH) to losartan- or atenolol-based therapy for a mean of 4.7 years, with 1,970 (21.4%) taking aspirin at baseline. The primary composite end point (CEP) included cardiovascular death, stroke, and myocardial infarction (MI). The present cohort was stratified by aspirin use at baseline.
  
  
  RESULTS
  Blood pressures were reduced similarly in the losartan with aspirin (n = 1,004) and atenolol with aspirin (n = 966) groups. The CEP was reduced by 32% (95% confidence interval 0.55 to 0.86, p = 0.001) with losartan with aspirin compared to atenolol with aspirin, adjusted for Framingham risk score and LVH. The test for treatment versus aspirin interaction, excluding other covariates, was significant for the CEP (p = 0.016) and MI (p = 0.037).
  
  
  CONCLUSIONS
  There was a statistical interaction between treatment and aspirin in the LIFE study, with significantly greater reductions for the CEP and MI with losartan in patients using aspirin than in patients not using aspirin at baseline. Further studies are needed to clarify whether this represents a pharmacologic interaction or a selection by aspirin use of patients more likely to respond to losartan treatment.
authors.affiliation: Department of Cardiology, Ullevaal University Hospital, Oslo, Norway. eigil.fossum@medisin.uio.no
authors.forename: Eigil
authors.initials: E
authors.lastname: Fossum
authors.forename: Andreas
authors.initials: A
authors.lastname: Moan
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.forename: Stevo
authors.initials: S
authors.lastname: Julius
authors.forename: Steven M
authors.initials: SM
authors.lastname: Snapinn
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Edelman
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Frej
authors.initials: F
authors.lastname: Fyhrquist
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Krister
authors.initials: K
authors.lastname: Kristianson
authors.forename: Ole
authors.initials: O
authors.lastname: Lederballe-Pedersen
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lindholm
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Per
authors.initials: P
authors.lastname: Omvik
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Hans
authors.initials: H
authors.lastname: Wedel
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D001262:Atenolol / Q000009:adverse effects / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy*; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D001262:Atenolol; D019808:Losartan; D001241:Aspirin