CLINICAL STUDY: ANGIOTENSIN ANTAGONISTS AND HEART FAILURE
Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study
Maylene Wong, MD, FACC*,*,
Lidia Staszewsky, MD ,
Roberto Latini, MD,
Simona Barlera, MS,
Alberto Volpi, MD, FACC ,
Yann-Tong Chiang, PhD ,
Raymond L. Benza, MD, FACC||,
Sidney O. Gottlieb, MD, FACC¶,
Thomas D. Kleemann, MD#,
Franco Rosconi, MD**,
Pieter M. Vandervoort, MD, FACC,
Jay N. Cohn, MD, FACC Val-HeFT Heart Failure Trial Investigators
* VA Greater Los Angeles Healthcare System and University of California at Los Angeles, California, USA
Istituto Mario Negri, Milan, Italy
Istituto Mario Negri and "C Borella" Hospital, Milan, Italy
Novartis Pharmaceuticals, East Orange, New Jersey, USA
|| University of Alabama, Birmingham, Alabama, USA
¶ Mid-Atlantic Cardiovascular Associates, Baltimore, Maryland, USA
# Herzzentrum Ludwigshafen, Ludwigshafen, Germany
** Ospedale Passirana di Rho, Milan, Italy
Hartcentrum Limburg, Genk, Belgium
University of Minnesota, Minneapolis, Minnesota, USA
Manuscript received January 29, 2002;
revised manuscript received May 29, 2002,
accepted May 31, 2002.
* Reprint requests and correspondence: Dr. Maylene Wong, (00QM), VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, California 90073, USA.
maylene.wong{at}med.va.gov
OBJECTIVES: The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy.
BACKGROUND: The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling.
METHODS: At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF.
RESULTS: Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 ± 0.5 versus 3.7 ± 0.5 (cm/m2) and 26.6 ± 7.3 versus 26.9 ± 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were –0.12 ± 0.4 versus –0.05 ± 0.4 (cm/m2), p < 0.00001 for LVIDd, and +4.5 ± 8.9 versus +3.2 ± 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups.
CONCLUSIONS: The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.
|
Abbreviations and Acronyms
| | ACEI | | angiotensin-converting enzyme inhibitor | | ANCOVA | | analysis of covariance | | ARB | | angiotensin receptor blocker | | ANGII | | angiotensin II | | BB | | beta-blocker | | EF | | ejection fraction | | LV | | left ventricular | | LVIDd | | left ventricular internal diastolic diameter | | LVIDd/BSA | | left ventricular internal diastolic diameter/body surface area | | NYHA | | New York Heart Association | | RAAS | | renin-angiotensin-aldosterone system | | Val-HeFT | | Valsartan in Heart Failure Trial |
|
This article has been cited by other articles:
|
|
|
|
 
M. J. Haykowsky, J. R. Mackey, R. B. Thompson, L. W. Jones, and D. I. Paterson
Adjuvant Trastuzumab Induces Ventricular Remodeling Despite Aerobic Exercise Training
Clin. Cancer Res.,
August 1, 2009;
15(15):
4963 - 4967.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
e1 - e90.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, M. A. Silver, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation
J. Am. Coll. Cardiol.,
April 14, 2009;
53(15):
1343 - 1382.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2009 WRITING GROUP TO REVIEW NEW EVIDENCE AND UPDA, M. Jessup, W. T. Abraham, D. E. Casey, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. A. Konstam, D. M. Mancini, P. S. Rahko, et al.
2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
1977 - 2016.
[Full Text]
[PDF]
|
|
|
|
|
|
|
2005 WRITING COMMITTEE MEMBERS, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, et al.
2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: Developed in Collaboration With the International Society for Heart and Lung Transplantation
Circulation,
April 14, 2009;
119(14):
e391 - e479.
[Full Text]
[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]
|
|
|
|
|
|
|
U. Landmesser, K. C. Wollert, and H. Drexler
Potential novel pharmacological therapies for myocardial remodelling
Cardiovasc Res,
February 15, 2009;
81(3):
519 - 527.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Richards
Serial Measurements of Plasma B-Type Natriuretic Peptides: What Do They Tell Us?
J. Am. Coll. Cardiol.,
September 16, 2008;
52(12):
1004 - 1005.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schindler
ACE-inhibitor, AT1-receptor-antagonist, or both? A clinical pharmacologist`s perspective after publication of the results of ONTARGET
Therapeutic Advances in Cardiovascular Disease,
August 1, 2008;
2(4):
233 - 248.
[Abstract]
[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]
|
|
|
|
|
|
|
P. Ferdinandy, R. Schulz, and G. F. Baxter
Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning
Pharmacol. Rev.,
December 1, 2007;
59(4):
418 - 458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Cohn
Myocardial Structural Effects of Aldosterone Receptor Antagonism in Heart Failure
J. Am. Coll. Cardiol.,
August 14, 2007;
50(7):
597 - 599.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Ingelsson, J. Sundstrom, L. Lind, U. Riserus, A. Larsson, S. Basu, and J. Arnlov
Low-grade albuminuria and the incidence of heart failure in a community-based cohort of elderly men
Eur. Heart J.,
July 2, 2007;
28(14):
1739 - 1745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Haykowsky, Y. Liang, D. Pechter, L. W. Jones, F. A. McAlister, and A. M. Clark
A Meta-Analysis of the Effect of Exercise Training on Left Ventricular Remodeling in Heart Failure Patients: The Benefit Depends on the Type of Training Performed
J. Am. Coll. Cardiol.,
June 19, 2007;
49(24):
2329 - 2336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Taylor, S. Ziesche, C. W. Yancy, P. Carson, K. Ferdinand, M. Taylor, K. Adams, A. Y. Olukotun, E. Ofili, S. W. Tam, et al.
Early and Sustained Benefit on Event-Free Survival and Heart Failure Hospitalization From Fixed-Dose Combination of Isosorbide Dinitrate/Hydralazine: Consistency Across Subgroups in the African-American Heart Failure Trial
Circulation,
April 3, 2007;
115(13):
1747 - 1753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-Y. Chong and G. Y.H. Lip
Viewpoint: The prothrombotic state in heart failure: A maladaptive inflammatory response?
Eur J Heart Fail,
February 1, 2007;
9(2):
124 - 128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ohtani, M. Ohta, K. Yamamoto, T. Mano, Y. Sakata, M. Nishio, Y. Takeda, J. Yoshida, T. Miwa, M. Okamoto, et al.
Elevated cardiac tissue level of aldosterone and mineralocorticoid receptor in diastolic heart failure: beneficial effects of mineralocorticoid receptor blocker
Am J Physiol Regulatory Integrative Comp Physiol,
February 1, 2007;
292(2):
R946 - R954.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Birks, P. D. Tansley, J. Hardy, R. S. George, C. T. Bowles, M. Burke, N. R. Banner, A. Khaghani, and M. H. Yacoub
Left Ventricular Assist Device and Drug Therapy for the Reversal of Heart Failure
N. Engl. J. Med.,
November 2, 2006;
355(18):
1873 - 1884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Tsouli, E. N. Liberopoulos, D. N. Kiortsis, D. P. Mikhailidis, and M. S. Elisaf
Combined Treatment With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers: A Review of the Current Evidence
Journal of Cardiovascular Pharmacology and Therapeutics,
March 1, 2006;
11(1):
1 - 15.
[Abstract]
[PDF]
|
|
|
|
|
|
|
G. Nickenig, J. Ostergren, and H. Struijker-Boudier
Clinical Evidence for the Cardiovascular Benefits of Angiotensin Receptor Blockers
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2006;
7(1_suppl):
S1 - S7.
[Abstract]
[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]
|
|
|
|
|
|
|
P. Ferrazzi, M. L.S. Matteucci, M. Merlo, A. Iacovoni, G. Rescigno, M. Bottai, P. Parrella, L. Lorini, M. Senni, and A. Gavazzi
Surgical ventricular reverse remodeling in severe ischemic dilated cardiomyopathy: The relevance of the left ventricular equator as a prognostic factor
J. Thorac. Cardiovasc. Surg.,
February 1, 2006;
131(2):
357 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)
J. Am. Coll. Cardiol.,
September 20, 2005;
46(6):
1116 - 1143.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society
Circulation,
September 20, 2005;
112(12):
1825 - 1852.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Solomon, H. Skali, N. S. Anavekar, M. Bourgoun, S. Barvik, J. K. Ghali, J. W. Warnica, M. Khrakovskaya, J. M. O. Arnold, Y. Schwartz, et al.
Changes in Ventricular Size and Function in Patients Treated With Valsartan, Captopril, or Both After Myocardial Infarction
Circulation,
June 28, 2005;
111(25):
3411 - 3419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Grayburn, C. P. Appleton, A. N. DeMaria, B. Greenberg, B. Lowes, J. Oh, J. F. Plehn, P. Rahko, M. St. John Sutton, E. J. Eichhorn, et al.
Echocardiographic predictors of morbidity and mortality in patients with advanced heart failure: The Beta-blocker Evaluation of Survival Trial (BEST)
J. Am. Coll. Cardiol.,
April 5, 2005;
45(7):
1064 - 1071.
[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]
|
|
|
|
|
|
|
V. C. Lee, D. C. Rhew, M. Dylan, E. Badamgarav, G. D. Braunstein, and S. R. Weingarten
Meta-Analysis: Angiotensin-Receptor Blockers in Chronic Heart Failure and High-Risk Acute Myocardial Infarction
Ann Intern Med,
November 2, 2004;
141(9):
693 - 704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Chrysant and G. S. Chrysant
Pharmacological and Clinical Profile of Moexipril: A Concise Review
J. Clin. Pharmacol.,
August 1, 2004;
44(8):
827 - 836.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wong, L. Staszewsky, R. Latini, S. Barlera, R. Glazer, N. Aknay, A. Hester, I. Anand, and J. N. Cohn
Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data
J. Am. Coll. Cardiol.,
June 2, 2004;
43(11):
2022 - 2027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. McKelvie, J.-L. Rouleau, M. White, R. Afzal, J. B. Young, A. P. Maggioni, P. Held, and S. Yusuf
Comparative impact of enalapril, candesartan or metoprolol alone or in combination on ventricular remodelling in patients with congestive heart failure
Eur. Heart J.,
October 1, 2003;
24(19):
1727 - 1734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. N. Cohn, I. S. Anand, R. Latini, S. Masson, Y.-T. Chiang, and R. Glazer
Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure: Results From the Valsartan Heart Failure Trial
Circulation,
September 16, 2003;
108(11):
1306 - 1309.
[Abstract]
[Full Text]
[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]
|
|
|
|
