Document Detail

Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials.
MedLine Citation:
PMID:  17384438     Owner:  NLM     Status:  MEDLINE    
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: Identifier: NCT00071331
Mihai Gheorghiade; Marvin A Konstam; John C Burnett; Liliana Grinfeld; Aldo P Maggioni; Karl Swedberg; James E Udelson; Faiez Zannad; Thomas Cook; John Ouyang; Christopher Zimmer; Cesare Orlandi;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2007-03-25
Journal Detail:
Title:  JAMA     Volume:  297     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-29     Completed Date:  2007-03-30     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1332-43     Citation Subset:  AIM; IM    
Data Bank Information
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MeSH Terms
Administration, Oral
Aged, 80 and over
Benzazepines / therapeutic use*
Cardiovascular Agents / therapeutic use*
Diuretics / therapeutic use
Double-Blind Method
Drug Therapy, Combination
Furosemide / therapeutic use
Heart Failure / drug therapy*
Middle Aged
Receptors, Vasopressin / antagonists & inhibitors*
Reg. No./Substance:
0/Benzazepines; 0/Cardiovascular Agents; 0/Diuretics; 0/Receptors, Vasopressin; 150683-30-0/tolvaptan; 7LXU5N7ZO5/Furosemide
Comment In:
Curr Heart Fail Rep. 2009 Mar;6(1):3-4   [PMID:  19278050 ]
JAMA. 2007 Mar 28;297(12):1374-6   [PMID:  17384439 ]
Curr Cardiol Rep. 2008 May;10(3):166-7   [PMID:  18489858 ]

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