TY - JOUR
T1 - Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure
T2 - The EVEREST clinical status trials
AU - The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators
AU - Gheorghiade, Mihai
AU - Konstam, Marvin A.
AU - Burnett, John C.
AU - Grinfeld, Liliana
AU - Maggioni, Aldo P.
AU - Swedberg, Karl
AU - Udelson, James E.
AU - Zannad, Faiez
AU - Cook, Thomas
AU - Ouyang, John
AU - Zimmer, Christopher
AU - Orlandi, Cesare
AU - Konstam, M.
AU - Burnett, J.
AU - Miller, A.
AU - O’connor, C.
AU - Bahit, M. C.
AU - Carson, P.
AU - Haass, M.
AU - Patten, R.
AU - Hauptman, P.
AU - Pena, I.
AU - Metra, M.
AU - Oren, R.
AU - Roth, S.
AU - Sackner-Bernstein, J.
AU - Goldstein, S.
AU - Dargie, H.
AU - Demets, D.
AU - Dickstein, K.
AU - Greenberg, B.
AU - Lerman, J.
AU - Massie, B.
AU - Pitt, B.
AU - Bechhofer, R.
AU - Anderson, S.
AU - C.burnett, J.
AU - Udelson, J.
AU - Dieterich, H. A.
AU - Capkova, Z.
AU - Gadaleta, F.
AU - Mule, M.
AU - Principato, M. B.
AU - Benza, R.
AU - Vijay, K.
AU - Goldberg, M.
AU - Siegel, R.
AU - Aude, Y.
AU - Elkayam, U.
AU - Skopicki, H.
PY - 2007/3/28
Y1 - 2007/3/28
N2 - 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, doubleblind, 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.
AB - 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, doubleblind, 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.
UR - https://www.scopus.com/pages/publications/33947719178
U2 - 10.1001/jama.297.12.1332
DO - 10.1001/jama.297.12.1332
M3 - Article
C2 - 17384438
AN - SCOPUS:33947719178
SN - 0098-7484
VL - 297
SP - 1332
EP - 1343
JO - JAMA
JF - JAMA
IS - 12
ER -