Copyright © 1996 by the European Society of Cardiology.
© 1996 The European Society of Cardiology
What is the ideal study design for evaluation of treatment for heart failure?
Insights from trials assessing the effect of ACE inhibitors on exercise capacity
,
*Department of Medicine (Cardiology), Royal Postgraduate Medical School, Hammersmith Hospital London, U.K.
Department of Medicine, Ostra Hospital, University of Goteborg Goteborg, Sweden
Received 16 June 1995; accepted 11 July 1995.
Correspondence: John G. F. Cleland, MRC Clinical Research Initiative in Heart Failure, West Medical Building, University of Glasgow, Glasgow G12 8QQ
Abstract
There is a wealth of evidence that angiotensin converting enzyme (ACE) inhibitors improve symptoms, morbidity and mortality in patients with heart failure. In this context the use of ACE inhibitors could be considered a tool with which to assess the effect of trial design and methodology on the ability to detect improvement in symptoms and exercise performance.
Thirty-five published, double-blind, randomized placebocontrolled trials, involving a total of 3411 patients, which compared the effect of ACE inhibitors and placebo on exercise capacity in patients with symptomatic chronic heart failure were identified. Studies were examined in relation to whether they used cross-over or parallel group study design, study size, use of treadmill vs bicycle exercise test, year of publication, patient entry criteria, duration of follow-up and the particular ACE inhibitor used.
Exercise duration improved in 23 of the studies, while symptoms improved in 25 of the 33 studies which evaluated this. In the majority of the trials (27 of 33) there was concordance between the effect on symptoms and on exercise capacity. There were six trials which showed discrepant results. Study size, duration of follow-up and method of exercise testing used were found to be major factors affecting the outcome. Trials using treadmill exercise tests were more likely to be positive than those using bicycle ergometry. All nine trials with study size more than 50, follow-up of 3–6 months and using treadmill exercise tests showed improved exercise capacity as well as symptoms. These findings may be useful in designing future trials for evaluating treatment for heart failure.
Key Words: Heart failure • ACE inhibitors • exercise capacity • study design
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. M. O'Connor, D. J. Whellan, K. L. Lee, S. J. Keteyian, L. S. Cooper, S. J. Ellis, E. S. Leifer, W. E. Kraus, D. W. Kitzman, J. A. Blumenthal, et al. Efficacy and Safety of Exercise Training in Patients With Chronic Heart Failure: HF-ACTION Randomized Controlled Trial JAMA, April 8, 2009; 301(14): 1439 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Abdulla, J. Pogue, S. Z. Abildstrom, L. Kober, E. Christensen, M. A. Pfeffer, S. Yusuf, and C. Torp-Pedersen Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis Eur J Heart Fail, January 1, 2006; 8(1): 90 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A D Gavin and A D Struthers Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure Heart, June 1, 2005; 91(6): 749 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Olsson, K. Swedberg, A. L. Clark, K. K. Witte, and J. G.F. Cleland Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review Eur. Heart J., April 2, 2005; 26(8): 778 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Refsgaard 'This is a walking test, not a talking test': the six minute walking test in congestive heart failure Eur. Heart J., April 2, 2005; 26(8): 749 - 750. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tachibana, H.-J. Cheng, T. Ukai, A. Igawa, Z.-S. Zhang, W. C. Little, and C.-P. Cheng Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H914 - H922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Abdulla, S. Z. Abildstrom, E. Christensen, L. Kober, and C. Torp-Pedersen A meta-analysis of the effect of angiotensin-converting enzyme inhibitors on functional capacity in patients with symptomatic left ventricular systolic dysfunction Eur J Heart Fail, December 1, 2004; 6(7): 927 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Task Force Members, J. Lopez-Sendon, K. Swedberg, J. McMurray, J. Tamargo, A. P. Maggioni, H. Dargie, M. Tendera, F. Waagstein, J. Kjekshus, et al. Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease: The Task Force on ACE-inhibitors of the European Society of Cardiology Eur. Heart J., August 2, 2004; 25(16): 1454 - 1470. [Full Text] [PDF]
|
|
|
|
|
|
J. Abdulla, H. Burchardt, S. Z. Abildstrom, L. Kober, C. Torp-Pedersen, and On behalf of TRACE study group The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function Eur. Heart J., December 1, 2003; 24(23): 2116 - 2122. [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.A. Cooke, S.G. Williams, P. Marshall, J.K. Al-Timman, J. Shelbourne, D.J. Wright, and L.-B. Tan A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients Eur. Heart J., September 1, 2002; 23(17): 1360 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Linde, C. Leclercq, S. Rex, S. Garrigue, T. Lavergne, S. Cazeau, W. McKenna, M. Fitzgerald, J.-C. Deharo, C. Alonso, et al. Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study J. Am. Coll. Cardiol., July 3, 2002; 40(1): 111 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Houghton, M. Harrison, A. J. Cowley, and J. R. Hampton Assessing exercise capacity, quality of life and haemodynamics in heart failure: do the tests tell us the same thing? Eur J Heart Fail, June 1, 2002; 4(3): 289 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Leclercq and D. A. Kass Retiming the failing heart: principles and current clinical status of cardiac resynchronization J. Am. Coll. Cardiol., January 16, 2002; 39(2): 194 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-P. Cheng, T. Ukai, K. Onishi, N. Ohte, M. Suzuki, Z.-S. Zhang, H.-J. Cheng, H. Tachibana, A. Igawa, and W. C. Little The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1853 - H1860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cazeau, C. Leclercq, T. Lavergne, S. Walker, C. Varma, C. Linde, S. Garrigue, L. Kappenberger, G. A. Haywood, M. Santini, et al. Effects of Multisite Biventricular Pacing in Patients with Heart Failure and Intraventricular Conduction Delay N. Engl. J. Med., March 22, 2001; 344(12): 873 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Recommendations for exercise testing in chronic heart faliure patients Eur. Heart J., January 1, 2001; 22(1): 37 - 45. [PDF]
|
|
|
|
 |
|
 G. Gambassi, K. L. Lapane, A. Sgadari, P. Carbonin, C. Gatsonis, L. A. Lipsitz, V. Mor, R. Bernabei, and for the SAGE Study Group Effects of Angiotensin-Converting Enzyme Inhibitors and Digoxin on Health Outcomes of Very Old Patients With Heart Failure Arch Intern Med, January 10, 2000; 160(1): 53 - 60. [Abstract] [Full Text] [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]
|
|
|
|
|
|
J.G.F. Cleland and R. Narang Trial design for heart failure studies Eur. Heart J., November 1, 1999; 20(21): 1600 - 1601. [PDF]
|
|
|
|
 |
|
 D J Wright and L B Tan Classic techniques in medicine: The role of exercise testing in the evaluation and management of heart failure Postgrad. Med. J., August 1, 1999; 75(886): 453 - 458. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Eccles, N. Freemantle, and J. Mason North of England evidence based development project: guideline for angiotensin converting enzyme inhibitors in primary care management of adults with symptomatic heart failure BMJ, May 2, 1998; 316(7141): 1369 - 1375. [Full Text]
|
|