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Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.

Publication ,  Journal Article
Gheorghiade, M; Konstam, MA; Burnett, JC; Grinfeld, L; Maggioni, AP; Swedberg, K; Udelson, JE; Zannad, F; Cook, T; Ouyang, J; Zimmer, C ...
Published in: JAMA
March 28, 2007

CONTEXT: Heart failure causes more than 1 million US hospitalizations yearly, mostly related to congestion. Tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, shows promise in this condition. OBJECTIVE: To evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure. DESIGN, SETTING, AND PATIENTS: Two identical prospective, randomized, double-blind, placebo-controlled trials at 359 sites in North America, South America, and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and February 3, 2006. A total of 2048 (trial A) and 2085 (trial B) patients hospitalized with heart failure and congestion were studied. INTERVENTION: Patients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission. MAIN OUTCOME MEASURES: Primary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier. Secondary end points included dyspnea (day 1), global clinical status (day 7 or discharge), body weight (days 1 and 7 or discharge), and peripheral edema (day 7 or discharge). RESULTS: Rank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs 0.99 [0.44]; and trial B, 1.07 [0.42] vs 0.97 [0.43]; both trials P<.001). Mean (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83] kg; P<.001; and trial B, 1.82 [2.01] vs 0.95 [1.85] kg; P<.001) and day 7 or discharge (trial A, 3.35 [3.27] vs 2.73 [3.34] kg; P<.001; and trial B, 3.77 [3.59] vs 2.79 [3.46] kg; P<.001), whereas improvements in global clinical status were not different between groups. More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and trial B, respectively) vs patients receiving placebo (646 [70.6%] and 597 [65.3%], respectively) reported improvement in dyspnea at day 1 (both trials P<.001). Edema at day 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach significance in trial A (P = .07). Serious adverse event frequencies were similar between groups, without excess renal failure or hypotension. CONCLUSION: In patients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diuretics improved many, though not all, heart failure signs and symptoms, without serious adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00071331

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Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

March 28, 2007

Volume

297

Issue

12

Start / End Page

1332 / 1343

Location

United States

Related Subject Headings

  • Tolvaptan
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heart Failure
  • General & Internal Medicine
  • Furosemide
  • Female
  • Drug Therapy, Combination
 

Citation

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Gheorghiade, M., Konstam, M. A., Burnett, J. C., Grinfeld, L., Maggioni, A. P., Swedberg, K., … Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators, . (2007). Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA, 297(12), 1332–1343. https://doi.org/10.1001/jama.297.12.1332
Gheorghiade, Mihai, Marvin A. Konstam, John C. Burnett, Liliana Grinfeld, Aldo P. Maggioni, Karl Swedberg, James E. Udelson, et al. “Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.JAMA 297, no. 12 (March 28, 2007): 1332–43. https://doi.org/10.1001/jama.297.12.1332.
Gheorghiade M, Konstam MA, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007 Mar 28;297(12):1332–43.
Gheorghiade, Mihai, et al. “Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.JAMA, vol. 297, no. 12, Mar. 2007, pp. 1332–43. Pubmed, doi:10.1001/jama.297.12.1332.
Gheorghiade M, Konstam MA, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C, Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007 Mar 28;297(12):1332–1343.
Journal cover image

Published In

JAMA

DOI

EISSN

1538-3598

Publication Date

March 28, 2007

Volume

297

Issue

12

Start / End Page

1332 / 1343

Location

United States

Related Subject Headings

  • Tolvaptan
  • Middle Aged
  • Male
  • Humans
  • Hospitalization
  • Heart Failure
  • General & Internal Medicine
  • Furosemide
  • Female
  • Drug Therapy, Combination