Skip to main content
Log in

ACE-Inhibition and Angiotensin II Receptor Blockers in Chronic Heart Failure: Pathophysiological Consideration of the Unresolved Battle

  • Letter to the Editor
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Reducing the effects of angiotensin II by blockade of AT1-receptors may be superior to inhibition of angiotensin II formation by angiotensin converting enzyme (ACE) inhibitors in chronic heart failure (CHF) patients. However, the results of several trials did not fulfil this expectation. In both ELITE II with symptomatic CHF patients and in OPTIMAAL involving high risk patients after acute myocardial infarction, angiotensin II type I (AT1) receptor blocker (ARB) losartan did not prove to be superior to captopril. There are several potential reasons, why ARBs did not fare better than ACE inhibitors. Although AT1-receptor blockade may block the effects of non-ACE pathways of tissue angiotensin II formation, no clinical evidence is available that a more powerful inhibition of the tissue renin-angiotensin system brings improved survival. The choice of patients for clinical trials of HF therapy is not based on the level of neurohumoral activation. Thus, the more effective attenuation of angiotensin II action with ARBs may not bring additional benefits. The potential antiremodeling effect of ARBs through the stimulation of AT2 receptors by angiotensin II could be counterbalanced by a failure of AT1-receptor blockers to enhance bradykinin, nitric oxide and prostacyclin formation with antigrowth properties. Although ACE-inhibitors seem to have slightly better results at present than AT1 blockers in the battle on heart failure patient, future trials will decide which is the definitive winner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Pitt B, Segal R, Martinez FA, et al. on behalf of the ELITE Study Investigators. Randomised trial of losartan versus captopril in patients over 65 with heart failure. Lancet 1997;349:747-752.

    Google Scholar 

  2. Pitt B, Poole-Wilson PA, Segal R, et al. on behalf of the ELITE II investigators. Effect of losartan compared with captopril in patients with symptomatic heart failure: Randomised trial-The Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-1587.

    Google Scholar 

  3. Dickstein K, Kjekshus J, and the OPTIMAAL Steering Committee, for the OPTIMAAL Study Group. Effect of losartan and captopril on mortality and morbidity in highrisk patients after acute myocardial infarction: The OPTIMAAL randomised trial. Lancet 2002;360:752-760.

    Google Scholar 

  4. Jong P, Demers C, McKelvie RS, Liu PP. Angiotensin receptors blockers in heart failure: Meta-analysis of randomised controlled trials. J Am Coll Cardiol 2002;39:463-470.

    Google Scholar 

  5. The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: Results of the Co-operative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429-1435.

    Google Scholar 

  6. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.

    Google Scholar 

  7. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbid dinitrate in the treatment of congestive chronic heart failure. N Engl J Med 1991;325:303-310.

    Google Scholar 

  8. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993;342:821-828.

    Google Scholar 

  9. Pfeffer MA, Braunwald E, Moyé LA, et al. (on behalf of the SAVE investigators). Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669-677.

    Google Scholar 

  10. Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995;333:1670-1676.

    Google Scholar 

  11. Remme WJ, Swedberg K; European Society of Cardiology. Comprehensive guidelines for the diagnosis and treatment of chronic heart failure. Task force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology. Eur J Heart Fail 2002;4:11-22.

    Google Scholar 

  12. Hunt SA, Baker DW, Chin MH, et al. American College of Cardiology; American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: Executive summary. J Heart Lung Transplant 2002;21:189-203.

    Google Scholar 

  13. Weber KT, Sun Y, Katwa LC, Cleutjens JP. Connective tissue: A metabolic entity? J Mol Cell Cardiol 1995;27:107-120.

    Google Scholar 

  14. Urata H, Ganten G. Cardiac angiotensin II formation: The angiotensin-I converting enzyme and human chymase. Eur Heart J 1994;14(Suppl I):177-182.

    Google Scholar 

  15. Dzau VJ, Bernstein K, Celermajer D, et al. The relevance of tissue angiotensin-converting enzyme: Manifestations in mechanistic and endpoint data. Am J Cardiol 2001;88(Suppl):1L-20L.

    Google Scholar 

  16. Tang WH, Vagelos RH, Yee YG, et al. Neurohormonal and clinical responses to high-versus low-dose enalapril therapy in chronic heart failure. J Am Coll Cardiol 2002;39:70-78.

    Google Scholar 

  17. Martineau P, Goulet J. New competition in the realm of rennin-angiotensin axis inhibition: The angiotensin II receptor antagonists in congestive heart failure. Ann Pharmacother 2001;35:71-84.

    Google Scholar 

  18. Pitt B. “Escape” of aldosterone production in patient with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: Implications for therapy. Cardiovasc Drug Ther 1995;9:145-149.

    Google Scholar 

  19. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Circulation 1999;100:1056-1064.

    Google Scholar 

  20. Roig E, Perez-Villa F, Morales M, et al. Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Eur Heart J 2000;21:53-57.

    Google Scholar 

  21. Dinh DT, Frauman AG, Johnston CI, Fabiani ME. Angiotensin receptors: Distribution, signalling and function. Clin Sci 2001;100:481-492.

    Google Scholar 

  22. Israili ZH, Hall WD. Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy: Areview of the literature and pathophysiology. Ann Int Med 1992;117:234-242.

    Google Scholar 

  23. Simko F, Simko J. The potential role of nitric oxide in the hypertrophic growth of the left ventricle (review). Physiol Res 2000;49:37-46.

    Google Scholar 

  24. Schneider MD, Lorell BH. AT2, judgment day. Which angiotensin receptor is the culprit in cardiac hypertrophy? Circulation 2001;104:247-248.

    Google Scholar 

  25. Cohn JN, Tognoni G. A randomised trial of the angiotensinreceptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-1675.

    Google Scholar 

  26. Swedberg K, Pfeffer M, Granger C, et al. Candesartan in heart failure-Assessment of reduction in mortality and morbidity (CHARM): Rationale and design. Charm-Programme Investigators. J Card Fail 1999;5:276-282.

    Google Scholar 

  27. Pfeffer M, McMurray J, Leizorovicz A, Maggioni AP, Reuleau J-L, Van de Werf F, for the VALIANT Investigators. Valsartan in Acute Myocardial Infarction Trial (VALIANT): Rationale and design. Am Heart J 2000;140:727-734.

    Google Scholar 

  28. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. New Engl J Med 1999;341:10-19.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simko, F., Simko, J. & Fabryova, M. ACE-Inhibition and Angiotensin II Receptor Blockers in Chronic Heart Failure: Pathophysiological Consideration of the Unresolved Battle. Cardiovasc Drugs Ther 17, 287–290 (2003). https://doi.org/10.1023/A:1026215712983

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026215712983

Navigation