Circulation. 2002;106:2454-2458
Published online before print October 21, 2002, doi: 10.1161/01.CIR.0000036747.68104.AC
Published online before print October 21, 2002, doi: 10.1161/01.CIR.0000036747.68104.AC
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:2454.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Valsartan on Circulating Brain Natriuretic Peptide and Norepinephrine in Symptomatic Chronic Heart Failure
The Valsartan Heart Failure Trial (Val-HeFT)
From the Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy (R.L., S.M., M.S., P.C., G.T.); VA Medical Center (I.A.) and University of Minnesota, Minneapolis (D.J., J.N.C.); ANMCO Research Center, Florence, Italy (A.P.M.); Novartis Pharmaceuticals Corp, East Hanover, NJ (Y.-T.C.); Ospedale "Luigi Sacco," Milan, Italy (M.B.); Amphia Hospital, Breda, the Netherlands (P.H.J.M.D.); and St Elisabeth Ziekenhuis, Tilburg, the Netherlands (N.J.H.).
Correspondence to Roberto Latini, MD, Istituto "Mario Negri," Via Eritrea, 62, 20157, Milan, Italy. E-mail latini{at}marionegri.it
Background— Brain natriuretic peptide (BNP) and norepinephrine (NE) are strongly related to severity of and are independent predictors of outcome in heart failure. The long-term effects of angiotensin receptor blockers on BNP and NE in heart failure patients are not known.
Methods and Results— Both BNP and NE were measured in 4284 patients randomized to valsartan or placebo in the Valsartan Heart Failure Trial (Val-HeFT) at baseline and 4, 12, and 24 months after randomization. The effects of valsartan were tested by ANCOVA, controlling for baseline values and concomitant ACE inhibitors and/or ß-blockers. BNP and NE concentrations were similar at baseline in the 2 groups and were decreased by valsartan starting at 4 months and up to 24 months. BNP increased over time in the placebo group. At the end point, least-squares mean (±SEM) BNP increased from baseline by 23±5 pg/mL in the placebo group (n=1979) but decreased by 21±5 pg/mL (n=1940) in the valsartan group (P<0.0001). NE increased by 41±6 pg/mL (n=1979) and 12±6 pg/mL (n=1941) for placebo and valsartan, respectively (P=0.0003). Concomitant therapy with both ACE inhibitors and ß-blockers significantly reduced the effect of valsartan on BNP but not on NE (P for interaction=0.0223 and 0.2289, respectively).
Conclusions— In Val-HeFT, the largest neurohormone study in patients with symptomatic chronic heart failure, BNP and NE rose over time in the placebo group. Valsartan caused sustained reduction in BNP and attenuated the increase in NE over the course of the study. These neurohormone effects of valsartan are consistent with the clinical benefits reported in Val-HeFT.
Key Words: heart failure • angiotensin • natriuretic peptides • norepinephrine • trials
This article has been cited by other articles:
 |
|
 |
|
  Does BNP testing aid diagnosis of heart failure? DTB, October 1, 2009; 47(10): 110 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Parthasarathy, B. Pieske, M. Weisskopf, C. D. Andrews, P. Brunel, A. D. Struthers, and T. M. MacDonald A randomized, double-blind, placebo-controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction Eur J Heart Fail, October 1, 2009; 11(10): 980 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S Sever, A. H Gradman, and M. Azizi Managing cardiovascular and renal risk: the potential of direct renin inhibition Journal of Renin-Angiotensin-Aldosterone System, June 1, 2009; 10(2): 65 - 76. [Abstract] [PDF]
|
|
|
|
 |
|
 M. White, J.-L. Rouleau, R. Afzal, J. Floras, S. Yusuf, and R. S. McKelvie Effects of enalapril, candesartan or both on neurohumoral activation and LV volumes and function in patients with heart failure not treated with a beta-blocker Therapeutic Advances in Cardiovascular Disease, April 1, 2009; 3(2): 113 - 121. [Abstract] [PDF]
|
|
|
|
|
|
A. Boccanelli, G. F. Mureddu, G. Cacciatore, F. Clemenza, A. Di Lenarda, A. Gavazzi, M. Porcu, R. Latini, D. Lucci, A. P. Maggioni, et al. Anti-remodelling effect of canrenone in patients with mild chronic heart failure (AREA IN-CHF study): final results Eur J Heart Fail, January 1, 2009; 11(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J.V. McMurray, B. Pitt, R. Latini, A. P. Maggioni, S. D. Solomon, D. L. Keefe, J. Ford, A. Verma, J. Lewsey, and for the Aliskiren Observation of Heart Failure Tre Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure Circ Heart Fail, May 1, 2008; 1(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S. Anand, T. S. Rector, M. Kuskowski, S. Thomas, N.J. Holwerda, and J. N. Cohn Effect of Baseline and Changes in Systolic Blood Pressure Over Time on the Effectiveness of Valsartan in the Valsartan Heart Failure Trial Circ Heart Fail, May 1, 2008; 1(1): 34 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pfister, H. Diedrichs, A. Schiedermair, S. Rosenkranz, M. Hellmich, E. Erdmann, and C. A. Schneider Prognostic impact of NT-proBNP and renal function in comparison to contemporary multi-marker risk scores in heart failure patients Eur J Heart Fail, March 1, 2008; 10(3): 315 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.W. Nielsen, P.J. Cowburn, A. Sajadieh, J.J. Morton, H. Dargie, and T. McDonagh Value of BNP to estimate cardiac risk in patients on cardioactive treatment in primary care Eur J Heart Fail, December 1, 2007; 9(12): 1178 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.H. Wilson Tang, G. S. Francis, D. A. Morrow, L. K. Newby, C. P. Cannon, R. L. Jesse, A. B. Storrow, R. H. Christenson, COMMITTEE MEMBERS, R. H. Christenson, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure Circulation, July 31, 2007; 116(5): e99 - e109. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jourdain, G. Jondeau, F. Funck, P. Gueffet, A. Le Helloco, E. Donal, J. F. Aupetit, M. C. Aumont, M. Galinier, J. C. Eicher, et al. Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure: The STARS-BNP Multicenter Study J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1733 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. M. Felker, J. W. Petersen, and D. B. Mark Natriuretic peptides in the diagnosis and management of heart failure. Can. Med. Assoc. J., September 12, 2006; 175(6): 611 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Cohn Efficacy and Safety in Clinical Trials in Cardiovascular Disease J. Am. Coll. Cardiol., August 1, 2006; 48(3): 430 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Lainchbury, R. W. Troughton, C. M. Frampton, T. G. Yandle, A. Hamid, M. G. Nicholls, and A. M. Richards NTproBNP-guided drug treatment for chronic heart failure: design and methods in the "BATTLESCARRED" trial Eur J Heart Fail, August 1, 2006; 8(5): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Masson, R. Latini, I. S. Anand, T. Vago, L. Angelici, S. Barlera, E. D. Missov, A. Clerico, G. Tognoni, J. N. Cohn, et al. Direct Comparison of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in a Large Population of Patients with Chronic and Symptomatic Heart Failure: The Valsartan Heart Failure (Val-HeFT) Data Clin. Chem., August 1, 2006; 52(8): 1528 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.A. Gould, J. D'Agostino, H.G. Schneider, and D.M. Kaye Influence of atrial fibrillation on cardiac brain natriuretic peptide release during haemodynamic stress in heart failure Eur J Heart Fail, May 1, 2006; 8(3): 263 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. McKie, R. J. Rodeheffer, A. Cataliotti, F. L. Martin, L. H. Urban, D. W. Mahoney, S. J. Jacobsen, M. M. Redfield, and J. C. Burnett Jr Amino-Terminal Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide: Biomarkers for Mortality in a Large Community-Based Cohort Free of Heart Failure Hypertension, May 1, 2006; 47(5): 874 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P Liu, A. Maggioni, and E. J Velazquez Use of Valsartan in Post-Myocardial Infarction and Heart Failure Patients Journal of Renin-Angiotensin-Aldosterone System, March 1, 2006; 7(1_suppl): S19 - S22. [Abstract] [PDF]
|
|
|
|
 |
|
 S. D.R. Thackray, K. Witte, J. Ghosh, N. Nikitin, A. Anderson, A. Rigby, K. Goode, A. L. Clark, and J. G.F. Cleland N-terminal brain natriuretic peptide as a screening tool for heart failure in the pacemaker population Eur. Heart J., February 2, 2006; 27(4): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Passino, R. Poletti, F. Bramanti, C. Prontera, A. Clerico, and M. Emdin Neuro-hormonal activation predicts ventilatory response to exercise and functional capacity in patients with heart failure Eur J Heart Fail, January 1, 2006; 8(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Morrow, J. A. de Lemos, M. A. Blazing, M. S. Sabatine, S. A. Murphy, P. Jarolim, H. D. White, K. A. A. Fox, R. M. Califf, E. Braunwald, et al. Prognostic Value of Serial B-Type Natriuretic Peptide Testing During Follow-up of Patients With Unstable Coronary Artery Disease JAMA, December 14, 2005; 294(22): 2866 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M Bettencourt Clinical usefulness of B-type natriuretic peptide measurement: present and future perspectives Heart, November 1, 2005; 91(11): 1489 - 1494. [Full Text] [PDF]
|
|
|
|
 |
|
 T. L Ripley Valsartan in Chronic Heart Failure Ann. Pharmacother., March 1, 2005; 39(3): 460 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J.V. McMurray, M. A. Pfeffer, K. Swedberg, and V. J. Dzau Which Inhibitor of the Renin-Angiotensin System Should Be Used in Chronic Heart Failure and Acute Myocardial Infarction? Circulation, November 16, 2004; 110(20): 3281 - 3288. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Campana, M. Pasotti, L. Monti, M. Revera, A. Serio, L. Nespoli, G. Magrini, L. Scelsi, S. Ghio, and L. Tavazzi The evaluation of right ventricular performance in different clinical models of heart failure Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F61 - F67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bruins, M. R. Fokkema, J. W.P. Romer, M. J.L. DeJongste, F. P.L. van der Dijs, J. M.W. van den Ouweland, and F. A.J. Muskiet High Intraindividual Variation of B-Type Natriuretic Peptide (BNP) and Amino-Terminal proBNP in Patients with Stable Chronic Heart Failure Clin. Chem., November 1, 2004; 50(11): 2052 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bettencourt, A. Azevedo, J. Pimenta, F. Frioes, S. Ferreira, and A. Ferreira N-Terminal-Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients Circulation, October 12, 2004; 110(15): 2168 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Luchner and H Schunkert Interactions between the sympathetic nervous system and the cardiac natriuretic peptide system Cardiovasc Res, August 15, 2004; 63(3): 443 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Cohn, A. A. Quyyumi, N. K. Hollenberg, and K. A. Jamerson Surrogate Markers for Cardiovascular Disease: Functional Markers Circulation, June 29, 2004; 109(25_suppl_1): IV-31 - IV-46. [Full Text] [PDF]
|
|
|
|
|
|
P. Hildebrandt, M. Boesen, M. Olsen, K. Wachtell, and B. Groenning N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis Eur J Heart Fail, March 15, 2004; 6(3): 313 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Hartmann, M. Packer, A. J.S. Coats, M. B. Fowler, H. Krum, P. Mohacsi, J. L. Rouleau, M. Tendera, A. Castaigne, J. Trawinski, et al. NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy Eur J Heart Fail, March 15, 2004; 6(3): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bettencourt NT-proBNP and BNP: biomarkers for heart failure management Eur J Heart Fail, March 15, 2004; 6(3): 359 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schafer, D. Fraccarollo, P. Tas, I. Schmidt, G. Ertl, and J. Bauersachs Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism Eur J Heart Fail, March 1, 2004; 6(2): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. McMurray Angiotensin inhibition in heart failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1_suppl): S17 - S22. [Abstract] [PDF]
|
|
|
|
|
|
M. M. Givertz and E. Braunwald Neurohormones in heart failure: predicting outcomes, optimizing care Eur. Heart J., February 2, 2004; 25(4): 281 - 282. [Full Text] [PDF]
|
|
|
|
|
|
R. Latini, S. Masson, I. Anand, M. Salio, A. Hester, D. Judd, S. Barlera, A. P Maggioni, G. Tognoni, J. N Cohn, et al. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT Eur. Heart J., February 2, 2004; 25(4): 292 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. de Denus, C. Pharand, and D. R. Williamson Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone Chest, February 1, 2004; 125(2): 652 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kyuma, T. Nakata, A. Hashimoto, K. Nagao, H. Sasao, T. Takahashi, K. Tsuchihashi, and K. Shimamoto Incremental Prognostic Implications of Brain Natriuretic Peptide, Cardiac Sympathetic Nerve Innervation, and Noncardiac Disorders in Patients with Heart Failure J. Nucl. Med., February 1, 2004; 45(2): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Clerico and M. Emdin Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review Clin. Chem., January 1, 2004; 50(1): 33 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H Chee, K. Amudha, N. A Hussain, H. K Haizal, A.-M. J Choy, and C. C Lang Combination of drugs acting on the natriuretic system and the renin-angiotensin system in heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 140 - 148. [Abstract] [PDF]
|
|
|
|
|
|
J. Ostergren and J. J. McMurray Angiotensin receptor blockers in heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 171 - 175. [Abstract] [PDF]
|
|
|
|
|
|
S. Julius Bringing VALUE to LIFE Eur. Heart J. Suppl., April 1, 2003; 5(suppl_C): C5 - C8. [Abstract] [PDF]
|
|
|
|
|
|
J.N. Cohn Val-HeFT: changing the heart failure horizon Eur. Heart J. Suppl., April 1, 2003; 5(suppl_C): C25 - C28. [Abstract] [PDF]
|
|
|
|
|
|
I. S. Anand, L. D. Fisher, Y.-T. Chiang, R. Latini, S. Masson, A. P. Maggioni, R. D. Glazer, G. Tognoni, J. N. Cohn, and for the Val-HeFT Investigators Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT) Circulation, March 11, 2003; 107(9): 1278 - 1283. [Abstract] [Full Text] [PDF]
|
|