title: Predicting adverse events during angiotensin receptor blocker treatment in heart failure: results from the HEAAL trial.
abstract: OBJECTIVE
  In patients with heart failure and reduced left ventricular ejection fraction (HFrEF), renin-angiotensin-aldosterone system blockade reduces morbidity and mortality, but comes at an increased risk of adverse events (AEs). We utilized the HEAAL trial data to identify predictors of the most frequent investigator-reported AEs.
  
  
  RESULTS
  The HEAAL trial investigated the relationship between losartan dose and outcomes in patients with HFrEF. Cox proportional hazards modelling was used to investigate predictors of AEs and their association with subsequent outcomes. In multivariate analyses, kidney impairment, hyperkalaemia, and hypotension were more likely to occur in older patients (P < 0.01 for each), and those taking aldosterone blockers (P < 0.01 for each). Entry levels of creatinine, potassium, and systolic blood pressure were associated with their respective AEs (P < 0.001 for each). Diabetes, baseline haemoglobin, and diuretic use were predictors (P < 0.05) of kidney impairment and hyperkalaemia. Following AEs due to kidney impairment [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.91-2.50], hyperkalaemia (HR 1.53, 95% CI 1.27-1.85), and hypotension (HR 1.93, 95% CI 1.62-2.29), the risk of death increased compared with patients who did not experience these AEs.
  
  
  CONCLUSIONS
  While the risk of severe AEs is low, patients with HFrEF can be identified who are at increased risk during treatment with an angiotensin receptor blocker. AEs are associated with excess mortality, and at-risk patients should be monitored closely.
authors.affiliation: Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kiernan
authors.forename: Deborah
authors.initials: D
authors.lastname: Wentworth
authors.forename: Gary
authors.initials: G
authors.lastname: Francis
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Martinez
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D019808:Losartan