BACKGROUND:Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between baseline and trends in AVP with outcomes in patients hospitalized for worsening heart failure with reduced ejection fraction is unclear. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and ejection fraction ≤40%. The present analysis examined baseline and follow-up AVP levels in 3196 EVEREST patients with valid AVP measurements. Coprimary end points included all-cause mortality, and the composite of cardiovascular mortality or heart failure hospitalization. Median follow-up was 9.9 months. Times to events were compared with univariate log-rank tests and multivariable Cox regression models, adjusted for baseline risk factors. After adjusting for baseline covariates, elevated AVP levels were associated with increased all-cause mortality (hazard ratio, 1.33; 95% confidence interval, 1.13-1.55) and cardiovascular mortality or heart failure hospitalization (hazard ratio, 1.23; 95% confidence interval, 1.08-1.39). There was no interaction of baseline AVP with treatment assignment in terms of survival (P=0.515). Tolvaptan therapy increased the proportion of patients with elevated AVP (P<0.001), but this had no effect on mortality (hazard ratio, 0.95; 95% confidence interval, 0.72-1.24). CONCLUSIONS:Elevated baseline AVP level was independently predictive of mortality, but did not identify a group of patients who had improved outcomes with tolvaptan treatment. Tolvaptan treatment increased AVP levels during follow-up, but this incremental increase was not associated with worsened outcomes.
RCT Entities:
BACKGROUND:Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between baseline and trends in AVP with outcomes in patients hospitalized for worsening heart failure with reduced ejection fraction is unclear. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and ejection fraction ≤40%. The present analysis examined baseline and follow-up AVP levels in 3196 EVEREST patients with valid AVP measurements. Coprimary end points included all-cause mortality, and the composite of cardiovascular mortality or heart failure hospitalization. Median follow-up was 9.9 months. Times to events were compared with univariate log-rank tests and multivariable Cox regression models, adjusted for baseline risk factors. After adjusting for baseline covariates, elevated AVP levels were associated with increased all-cause mortality (hazard ratio, 1.33; 95% confidence interval, 1.13-1.55) and cardiovascular mortality or heart failure hospitalization (hazard ratio, 1.23; 95% confidence interval, 1.08-1.39). There was no interaction of baseline AVP with treatment assignment in terms of survival (P=0.515). Tolvaptan therapy increased the proportion of patients with elevated AVP (P<0.001), but this had no effect on mortality (hazard ratio, 0.95; 95% confidence interval, 0.72-1.24). CONCLUSIONS: Elevated baseline AVP level was independently predictive of mortality, but did not identify a group of patients who had improved outcomes with tolvaptan treatment. Tolvaptan treatment increased AVP levels during follow-up, but this incremental increase was not associated with worsened outcomes.
Authors: Véronique L Roger; Alan S Go; Donald M Lloyd-Jones; Emelia J Benjamin; Jarett D Berry; William B Borden; Dawn M Bravata; Shifan Dai; Earl S Ford; Caroline S Fox; Heather J Fullerton; Cathleen Gillespie; Susan M Hailpern; John A Heit; Virginia J Howard; Brett M Kissela; Steven J Kittner; Daniel T Lackland; Judith H Lichtman; Lynda D Lisabeth; Diane M Makuc; Gregory M Marcus; Ariane Marelli; David B Matchar; Claudia S Moy; Dariush Mozaffarian; Michael E Mussolino; Graham Nichol; Nina P Paynter; Elsayed Z Soliman; Paul D Sorlie; Nona Sotoodehnia; Tanya N Turan; Salim S Virani; Nathan D Wong; Daniel Woo; Melanie B Turner Journal: Circulation Date: 2011-12-15 Impact factor: 29.690
Authors: Peter S Pang; Marvin A Konstam; Holly B Krasa; Karl Swedberg; Faiez Zannad; John E A Blair; Christopher Zimmer; John R Teerlink; Aldo P Maggioni; John C Burnett; Liliana Grinfeld; John Ouyang; James E Udelson; Mihai Gheorghiade Journal: Eur Heart J Date: 2009-06-27 Impact factor: 29.983
Authors: Mihai Gheorghiade; Cesare Orlandi; John C Burnett; David Demets; Liliana Grinfeld; Aldo Maggioni; Karl Swedberg; James E Udelson; Faiez Zannad; Christopher Zimmer; Marvin A Konstam Journal: J Card Fail Date: 2005-05 Impact factor: 5.712
Authors: Mihai Gheorghiade; Wendy A Gattis; Christopher M O'Connor; Kirkwood F Adams; Uri Elkayam; Alejandro Barbagelata; Jalal K Ghali; Raymond L Benza; Frank A McGrew; Marc Klapholz; John Ouyang; Cesare Orlandi Journal: JAMA Date: 2004-04-28 Impact factor: 56.272
Authors: J L Rouleau; M Packer; L Moyé; J de Champlain; D Bichet; M Klein; J R Rouleau; B Sussex; J M Arnold; F Sestier Journal: J Am Coll Cardiol Date: 1994-09 Impact factor: 24.094
Authors: James E Udelson; Frank A McGrew; Enrique Flores; Hassan Ibrahim; Stewart Katz; Gregory Koshkarian; Terrence O'Brien; Marvin W Kronenberg; Christopher Zimmer; Cesare Orlandi; Marvin A Konstam Journal: J Am Coll Cardiol Date: 2007-05-18 Impact factor: 24.094
Authors: James A Iwaz; Elizabeth Lee; Hermineh Aramin; Danilo Romero; Navaid Iqbal; Matt Kawahara; Fatima Khusro; Brian Knight; Minal V Patel; Sumita Sharma; Alan S Maisel Journal: Drugs Date: 2016-02 Impact factor: 9.546
Authors: Melissa A Wasilewski; Valerie D Myers; Fabio A Recchia; Arthur M Feldman; Douglas G Tilley Journal: Cell Signal Date: 2015-07-30 Impact factor: 4.315
Authors: Weizhong Zhu; Douglas G Tilley; Valerie D Myers; Ryan C Coleman; Arthur M Feldman Journal: Mol Pharmacol Date: 2013-05-20 Impact factor: 4.436
Authors: Douglas G Tilley; Weizhong Zhu; Valerie D Myers; Larry A Barr; Erhe Gao; Xue Li; Jianliang Song; Rhonda L Carter; Catherine A Makarewich; Daohai Yu; Constantine D Troupes; Laurel A Grisanti; Ryan C Coleman; Walter J Koch; Steven R Houser; Joseph Y Cheung; Arthur M Feldman Journal: Circulation Date: 2014-09-09 Impact factor: 29.690