|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2000; 36:479-486 © 2000 by the American College of Cardiology Foundation |
a Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand
Manuscript received July 21, 1999; revised manuscript received January 28, 2000, accepted March 30, 2000.
Reprint requests and correspondence: Prof. Hamid Ikram, Department of Cardiology, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand t.nz
HAMIDI{at}chhlth.gov
OBJECTIVES
We sought to examine the effects of long-term vasopeptidase inhibition in patients with heart failure.
BACKGROUND
The long-term effects of omapatrilat, an agent that inhibits both neutral endopeptidase and angiotensin-converting enzyme, on clinical status, neurohormonal indexes and left ventricular function in patients with chronic heart failure (CHF) have not been previously documented.
METHODS
Forty-eight patients in New York Heart Association functional class II or III, with left ventricular ejection fraction (LVEF) 
40% and in sinus rhythm were randomized to a dose-ranging pilot study of omapatrilat for 12 weeks. Measurements were performed at baseline and 12 weeks.
RESULTS
There was an improvement in functional status, as reported by the patient (p < 0.001) and physician (p < 0.001) at 12 weeks. Dose-dependent improvements in LVEF (p < 0.001) and LV end-systolic wall stress (sigma) (p < 0.05) were seen, together with a reduction in systolic blood pressure (p < 0.05). There was evidence of a natriuretic effect (p < 0.001), and total blood volume decreased (p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (p < 0.01) in the high dose groups, with a reduction in predose plasma brain natriuretic peptide (p < 0.001) and epinephrine (p < 0.01) levels after 12 weeks of therapy. Omapatrilat was well tolerated.
CONCLUSIONS
The sustained hemodynamic, neurohumoral and renal effects of omapatrilat, together with improved functional status, suggest that vasopeptidase inhibition has potential as a new therapeutic modality for the treatment of CHF.
| ||||||||||||||||||||
This article has been cited by other articles:
|
|
 |
|
  Z. A. Abassi, A. Yahia, S. Zeid, T. Karram, E. Golomb, J. Winaver, and A. Hoffman Cardiac and renal effects of omapatrilat, a vasopeptidase inhibitor, in rats with experimental congestive heart failure Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H722 - H728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L.M. Cruden, K. A.A. Fox, C. A. Ludlam, N. R. Johnston, and D. E. Newby Neutral Endopeptidase Inhibition Augments Vascular Actions of Bradykinin in Patients Treated With Angiotensin-Converting Enzyme Inhibition Hypertension, December 1, 2004; 44(6): 913 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ebihara, G. Seno Di Marco, M. Aparecida Juliano, and D. E. Casarini Neutral endopeptidase expression in mesangial cells Journal of Renin-Angiotensin-Aldosterone System, December 1, 2003; 4(4): 228 - 233. [Abstract] [PDF]
|
|
|
|
 |
|
 D B McKenzie and A J Cowley Drug therapy in chronic heart failure Postgrad. Med. J., November 1, 2003; 79(937): 634 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Varagic, D. Susic, M. Slama, and E. D. Frohlich Omapatrilat Induces Profound Renal Vasodilation but Does Not Affect Coronary Hemodynamics Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2003; 8(2): 167 - 174. [Abstract] [PDF]
|
|
|
|
|
|
D. J. Campbell Vasopeptidase Inhibition: A Double-Edged Sword? Hypertension, March 1, 2003; 41(3): 383 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Pacific Study Group and B. Neal Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease Journal of Renin-Angiotensin-Aldosterone System, December 1, 2002; 3(4): 270 - 276. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Azizi, M. Lamarre-Cliche, A. Labatide-Alanore, A. Bissery, T. T. Guyene, and J. Menard Physiologic Consequences of Vasopeptidase Inhibition in Humans: Effect of Sodium Intake J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2454 - 2463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J J V McMurray Heart failure in 10 years time: focus on pharmacological treatment Heart, October 1, 2002; 88(90002): ii40 - 46. [Full Text] [PDF]
|
|
|
|
|
|
A. Dawson and A. D Struthers Review: Vasopeptidase inhibitors in heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2002; 3(3): 156 - 159. [Abstract] [PDF]
|
|
|
|
|
|
F. Regamey, M. Maillard, J. Nussberger, H. R. Brunner, and M. Burnier Renal Hemodynamic and Natriuretic Effects of Concomitant Angiotensin-Converting Enzyme and Neutral Endopeptidase Inhibition in Men Hypertension, September 1, 2002; 40(3): 266 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. McClean, H. Ikram, S. Mehta, J. T. Heywood, M. F. Rousseau, A. L. Niederman, R. F. Sequeira, E. Fleck, S. N. Singh, B. Coutu, et al. Vasopeptidase inhibition with omapatrilat in chronic heart failure: acute and long-term hemodynamic and neurohumoral effects J. Am. Coll. Cardiol., June 19, 2002; 39(12): 2034 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A Sagnella Review: Vasopeptidase inhibitors Journal of Renin-Angiotensin-Aldosterone System, June 1, 2002; 3(2): 90 - 95. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Cataliotti, G. Boerrigter, H. H. Chen, M. Jougasaki, L. C. Costello, T. Tsuruda, S.-C. Lee, L. S. Malatino, and J. C. Burnett Jr Differential Actions of Vasopeptidase Inhibition Versus Angiotensin-Converting Enzyme Inhibition on Diuretic Therapy in Experimental Congestive Heart Failure Circulation, February 5, 2002; 105(5): 639 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Corti, J. C. Burnett Jr, J. L. Rouleau, F. Ruschitzka, and T. F. Luscher Vasopeptidase Inhibitors: A New Therapeutic Concept in Cardiovascular Disease? Circulation, October 9, 2001; 104(15): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. TAAL, V. D. NENOV, W. WONG, S. R. SATYAL, O. SAKHAROVA, J. H. CHOI, J. L. TROY, and B. M. BRENNER Vasopeptidase Inhibition Affords Greater Renoprotection than Angiotensin-Converting Enzyme Inhibition Alone J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2051 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Sagnella Atrial natriuretic peptide mimetics and vasopeptidase inhibitors Cardiovasc Res, August 15, 2001; 51(3): 416 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R Kalra, S. D Anker, and A. J.S Coats Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin Cardiovasc Res, August 15, 2001; 51(3): 495 - 509. [Full Text] [PDF]
|
|
|
|
|
|
H. Peter Brunner-La Rocca, W. Kiowski, D. Ramsay, and G. Sutsch Therapeutic benefits of increasing natriuretic peptide levels Cardiovasc Res, August 15, 2001; 51(3): 510 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A Sagnella Practical implications of current natriuretic peptide research Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 304 - 315. [PDF]
|
|
|
|
 |
|
 Vasopeptidase Inhibition Associated with Favorable Clinical Effects in CHF Patients Journal Watch Cardiology, October 27, 2000; 2000(1027): 3 - 3. [Full Text]
|
|
|
|
|
|
R. W. Troughton, M. T. Rademaker, J. D. Powell, T. G. Yandle, E. A. Espiner, C. M. Frampton, M. G. Nicholls, and A. M. Richards Beneficial Renal and Hemodynamic Effects of Omapatrilat in Mild and Severe Heart Failure Hypertension, October 1, 2000; 36(4): 523 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Chen, J. G. Lainchbury, G. J. Harty, and J. C. Burnett Jr Maximizing the Natriuretic Peptide System in Experimental Heart Failure: Subcutaneous Brain Natriuretic Peptide and Acute Vasopeptidase Inhibition Circulation, February 26, 2002; 105(8): 999 - 1003. [Abstract] [Full Text] [PDF]
|
|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
