title: Efficacy and safety of angiotensin receptor blockade are not modified by aspirin in patients with chronic heart failure: a cohort study from the Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme.
abstract: OBJECTIVE
  It is unknown whether there is an interaction between aspirin and angiotensin receptor blockers on outcomes in patients with heart failure (HF).
  
  
  RESULTS
  The efficacy and safety of candesartan vs. placebo was assessed in 7599 patients with symptomatic HF and reduced or preserved left ventricular ejection fraction enrolled in the CHARM programme according to baseline aspirin use. Patients were randomized to candesartan or matching placebo and were followed for a median of 38 months. Aspirin was used in 4246 (55.9%) of patients at baseline. When compared with placebo, candesartan use was associated with lower event rates for cardiovascular (CV) death or HF hospitalization (primary outcome) in both the aspirin group (28 vs. 31.9%, HR 0.81, 95% CI 0.72-0.90) and non-aspirin group (33 vs. 38%, HR 0.81, 95% CI 0.72-0.91). Baseline aspirin use did not modify the effectiveness of candesartan in reducing the risk of CV death or HF hospitalization in CHARM overall (P = 0.64) or in the CHARM individual trials. In addition, there was no significant interaction between aspirin therapy and candesartan in terms of discontinuation of study drug due to adverse reactions (P = 0.72).
  
  
  CONCLUSIONS
  There appears to be no significant modification of the benefit of candesartan on CV mortality and morbidity outcomes or safety by concomitant use of aspirin in patients with chronic HF.
authors.affiliation: Department of Cardiology, The Methodist DeBakey Heart and Vascular Center, Houston, TX, USA.
authors.forename: Su Min
authors.initials: SM
authors.lastname: Chang
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Peter A
authors.initials: PA
authors.lastname: Johansson
authors.forename: Peter
authors.initials: P
authors.lastname: Kosolcharoen
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Eric L
authors.initials: EL
authors.lastname: Michelson
authors.forename: David R
authors.initials: DR
authors.lastname: Murray
authors.forename: Bertil
authors.initials: B
authors.lastname: Olofsson
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dunlap
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002318:Cardiovascular Diseases / Q000401:mortality; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013318:Stroke Volume; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D001241:Aspirin; C081643:candesartan