(Circulation. 1999;100:2224.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Improvement in Exercise Tolerance and Symptoms of Congestive Heart Failure During Treatment With Candesartan Cilexetil
From the Department of Internal Medicine II, University of Regensburg, Regensburg, Germany (G.A.J.R.); private practice, Munich, Germany (H.B.); Interne Oddeleni, Klinike Farmakologie, Ceske Budejovice, Czech Republic (P.P.); Interne Oddeleni, Nemocnice Milosrdynch (J.M.), and Interni Klinik, Fakultni Nemocnice Kralovski Vinohrady (R.S.), Prague, Czech Republic; private practice, Kleve, Germany (H.P.); private practice, Wiesbaden, Germany (V.v.B.); Takeda Europe R&D Centre Ltd, London, UK (M.G.); and Takeda Euro R&D GmbH, Frankfurt/Main, Germany (H.-J.A.).
Correspondence to Professor G.A.J. Riegger, Department of Internal Medicine II, University of Regensburg, Franz-Josef-Strauß-Allee 11, D-93053 Regensburg, Germany.
Background—The renin-angiotensin system plays an important part in the pathogenesis of congestive heart failure (CHF). This study evaluated the effect of an angiotensin II type 1 receptor antagonist on exercise tolerance and symptoms of CHF.
Methods and Results—In this multicenter, double-blind, parallel-group study, 844 patients with CHF were randomized to 12 weeks’ treatment with placebo (n=211) or candesartan cilexetil 4 mg (n=208), 8 mg (n=212), or 16 mg (n=213) after a 4-week placebo run-in period. Changes in exercise time, Dyspnea Fatigue Index score, NYHA functional class, and cardiothoracic ratio were determined. Candesartan cilexetil produced a dose-related improvement in exercise time. For the intention-to-treat population, the increase produced by candesartan cilexetil 16 mg was significantly greater than that produced by placebo (47.2 versus 30.8 seconds, P=0.0463). All doses of candesartan cilexetil significantly improved the Dyspnea Fatigue Index score relative to placebo. NYHA class improved more frequently in the candesartan cilexetil groups; the differences relative to placebo were not significant. The decrease in cardiothoracic ratio with candesartan 4 to 16 mg was small but statistically significant compared with placebo (all P<0.05). In all candesartan cilexetil groups, plasma renin activity and angiotensin II levels increased from baseline and aldosterone levels decreased in the 8- and 16-mg treatment groups. Candesartan cilexetil was well tolerated at all doses.
Conclusions—In summary, treatment with candesartan cilexetil demonstrated significant improvements in exercise tolerance, cardiothoracic ratio, and symptoms and signs of CHF and was well tolerated.
Key Words: heart failure • angiotensin • receptors • exercise
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
|
|
A. Dore, C. Houde, K.-L. Chan, A. Ducharme, P. Khairy, M. Juneau, F. Marcotte, and L.-A. Mercier Angiotensin Receptor Blockade and Exercise Capacity in Adults With Systemic Right Ventricles: A Multicenter, Randomized, Placebo-Controlled Clinical Trial Circulation, October 18, 2005; 112(16): 2411 - 2416. [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]
|
|
|
|
 |
|
 Z. Yuan, M. Nimata, T.-a. Okabe, K. Shioji, K. Hasegawa, T. Kita, and C. Kishimoto Olmesartan, a novel AT1 antagonist, suppresses cytotoxic myocardial injury in autoimmune heart failure Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1147 - H1152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Habash-Bseiso, R. Rokey, C. J. Berger, A. W. Weier, and P.-H. Chyou Accuracy of Noninvasive Ejection Fraction Measurement in a Large Community-Based Clinic Clin. Med. Res., May 1, 2005; 3(2): 75 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Yan, R. T. Yan, and P. P. Liu Narrative Review: Pharmacotherapy for Chronic Heart Failure: Evidence from Recent Clinical Trials Ann Intern Med, January 18, 2005; 142(2): 132 - 145. [Abstract] [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]
|
|
|
|
 |
|
 E. O'Meara, S. Solomon, J. McMurray, M. Pfeffer, S. Yusuf, E. Michelson, C. Granger, B. Olofsson, J. B. Young, and K. Swedberg Effect of candesartan on New York Heart Association functional class: Results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme Eur. Heart J., November 1, 2004; 25(21): 1920 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takahashi, T. Anzai, T. Yoshikawa, Y. Maekawa, K. Mahara, M. Iwata, H. K. Hammond, and S. Ogawa Angiotensin receptor blockade improves myocardial beta-adrenergic receptor signaling in postinfarction left ventricular remodeling: A possible link between beta-adrenergic receptor kinase-1 and protein kinase C epsilon isoform J. Am. Coll. Cardiol., January 7, 2004; 43(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Matsumori and on behalf of the assessment of response to candesa Efficacy and safety of oral candesartan cilexetil in patients with congestive heart failure Eur J Heart Fail, October 1, 2003; 5(5): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Varma, S. Sharma, S. Firoozi, W. J. McKenna, J.-C. Daubert, and Multisite Stimulation in Cardiomyopathy (MUSTIC) S Atriobiventricular pacing improves exercise capacity in patients with heart failure and intraventricular conduction delay J. Am. Coll. Cardiol., February 19, 2003; 41(4): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Ellis, A. K. Nightingale, D. J. Blackman, R. A. Anderson, C. Mumford, G. Timmins, D. Lang, S. K. Jackson, M. D. Penney, M. J. Lewis, et al. Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress Eur J Heart Fail, March 1, 2002; 4(2): 193 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jong, C. Demers, R. S. McKelvie, and P. P. Liu Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials J. Am. Coll. Cardiol., February 6, 2002; 39(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J V McMurray HEART FAILURE: Angiotensin receptor blockers for chronic heart failure and acute myocardial infarction Heart, July 1, 2001; 86(1): 97 - 103. [Full Text] [PDF]
|
|
|
|
|
|
M. Jain, H. DerSimonian, D. A. Brenner, S. Ngoy, P. Teller, A. S. B. Edge, A. Zawadzka, K. Wetzel, D. B. Sawyer, W. S. Colucci, et al. Cell Therapy Attenuates Deleterious Ventricular Remodeling and Improves Cardiac Performance After Myocardial Infarction Circulation, April 10, 2001; 103(14): 1920 - 1927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Jamali, W. H. W. Tang, U. N. Khot, and M. B. Fowler The Role of Angiotensin Receptor Blockers in the Management of Chronic Heart Failure Arch Intern Med, March 12, 2001; 161(5): 667 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Littmann, L. K. Stell, G.A.J. Riegger, H. Bouzo, P. Petr, J. Munz, R. Spacek, H. Pethig, V. von Behren, M. George, et al. Use of Placebo in Heart Failure Research Response Circulation, December 19, 2000; 102 (25): e187 - e188. [Full Text] [PDF]
|
|
|
|
 |
|
 M. S Weinberg, A. J Weinberg, and D. H Zappe Effectively targetting the renin-angiotensin-aldosterone system in cardiovascular and renal disease: rationale for using angiotensin II receptor blockers in combination with angiotensin-converting enzyme inhibitors Journal of Renin-Angiotensin-Aldosterone System, September 1, 2000; 1(3): 217 - 233. [PDF]
|
|
|
|
|
|
J. McMurray AT1 receptor antagonists---beyond blood pressure control: possible place in heart failure treatment Heart, September 1, 2000; 84(90001): 42i - 45. [Full Text]
|
|
|
|
|
|
J. McMurray and C. Berry Ongoing clinical trials with angiotensin II receptor antagonists in chronic heart failure and myocardial infarction Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2): 131 - 136. [PDF]
|
|
|
|
|
|
H. Schunkert The importance of early intervention in CHF -- signs and symptom relief Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1_suppl): 17 - 23. [Abstract] [PDF]
|
|
|
|
|
|
E. Erdmann, M. George, B. Voet, G. Belcher, D. Kolb, S. Hiemstra, M. Pietrek, and P. Held The safety and tolerability of candesartan cilexetil in CHF Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1_suppl): 31 - 36. [Abstract] [PDF]
|
|
|
|
|
|
J. N. Cohn Exercise Tolerance as a Guide to Therapeutic Efficacy for Heart Failure : The Potential for Angiotensin Receptor Blockers Circulation, November 30, 1999; 100(22): 2208 - 2209. [Full Text] [PDF]
|
|