title: The safety of intravenous diuretics alone versus diuretics plus parenteral vasoactive therapies in hospitalized patients with acutely decompensated heart failure: a propensity score and instrumental variable analysis using the Acutely Decompensated Heart Failure National Registry (ADHERE) database.
abstract: BACKGROUND
  The treatment of acute decompensated heart failure remains problematic and most often requires parenteral therapies. Significant concerns have been expressed regarding risks and benefits of individual therapies, especially nesiritide (NES), but few studies have compared the relative safety of varied intravenous therapies on clinical outcomes.
  
  
  METHODS
  We compared the safety of intravenous diuretics (DIUR), inotropes (INO), and vasodilators (nitroglycerin [NTG]) on mortality rates and worsening renal function in 99,963 inpatients with acutely decompensated heart failure (ADHF). Patients with a diagnosis of ADHF within 48 hours were grouped by intended primary treatment (intravenous agents administered during the first 2 hours of intravenous therapy). Treatments studied were (a) intended monotherapy (DIUR), (b) intended combination therapy (DIUR + NES, NTG, or INO), and (c) sequential therapy (intended DIUR monotherapy followed by a second agent administered >2 hours later). Propensity-matched cohorts and instrumental analysis were used to adjust for differences among patients in treatment groups.
  
  
  RESULTS
  Intended DIUR monotherapy yielded an unadjusted inpatient mortality rate of 3.2%. After intended DIUR monotherapy, inpatient mortality was not higher for sequential use of NES than for sequential use of NTG (3.4% vs 6.2%, P = .0028). In all regimens, INOs were associated with higher inpatient mortality than were diuretics or vasodilators used alone. The rate of worsening renal function was higher with combination of diuretic-based regimens with NES (risk ratio 1.44, P < .0001) or NTG (RR 1.2, P = .012) compared with diuretics alone.
  
  
  CONCLUSIONS
  Compared with alternative intravenous regimens, administration of vasodilators, including NES, was not associated with increased inpatient mortality. A large randomized controlled clinical trial is being planned to prospectively address the question of risks and benefits of NES for ADHF.
authors.affiliation: Midwest Heart Foundation, Lombard, IL, USA. mcostanzo@midwestheart.com
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Costanzo
authors.forename: R S
authors.initials: RS
authors.lastname: Johannes
authors.forename: Michael
authors.initials: M
authors.lastname: Pine
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: Mitchell
authors.initials: M
authors.lastname: Saltzberg
authors.forename: Joel
authors.initials: J
authors.lastname: Hay
authors.forename: Clyde W
authors.initials: CW
authors.lastname: Yancy
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D019992:Databases as Topic; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000009:adverse effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D004232:Diuretics; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain