Skip to main content
Log in

The angiotensin-converting enzyme inhibitor and aspirin interaction in congestive heart failure:Fear or reality?

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of therapy for congestive heart failure (CHF). Because ischemic heart disease is the most common cause of CHF, aspirin is frequently given concomitantly with ACE inhibitors in patients with CHF. Increased bradykinin levels, with the consequent enhanced synthesis of vasodilatory prostaglandins, appear to mediate a significant benefit of ACE inhibitor therapy in these patients. In contrast, aspirin inhibits cylcooxygenase, and thereby suppresses prostaglandin production. Thus, these counteracting effects on prostaglandins may result in antagonism between ACE inhibitor and aspirin therapy in heart failure patients. Several early reports questioned the safety of aspirin in CHF, and the potential antagonistic interaction between ACE inhibitors and aspirin in patients with heart failure has become the focus of both increasing research and intense debate. This article briefly highlights the theoretic considerations underlying this interaction, and reviews the available evidence for such an interaction from clinical trials.

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.

Similar content being viewed by others

References and Recommended Reading

  1. American Heart Association: 1997 Heart and Stroke Update: Statistical Update. Dallas: American Heart Association; 1996:1–29.

    Google Scholar 

  2. Kannel WB, Belanger AJ: Epidemiology of heart failure. Am Heart J 1991, 121:951–957.

    Article  PubMed  CAS  Google Scholar 

  3. Kjekshus J, Swedberg K, Snapinn S, for the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS) Trial Group: Effects of enalapril on long-term mortality in severe congestive heart failure. Am J Cardiol 1992, 69:103–107.

    Article  PubMed  CAS  Google Scholar 

  4. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. N Engl J Med 1991, 325:293–302.

    Article  Google Scholar 

  5. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators: Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992, 327:685–691.

    Article  Google Scholar 

  6. Pfeffer MA, Braunwald E, Moye LA, et al. for the Survival and Ventricular Enlargement (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.

    Article  PubMed  CAS  Google Scholar 

  7. Parmley WW: Pathophysiology of congestive heart failure. Am J Cardiol 1985, 56:7A-11A.

    Article  PubMed  CAS  Google Scholar 

  8. Teerlink JR, Goldhaber SZ, Pfeffer MA: An overview of contemporary etiologies of congestive heart failure. Am Heart J 1991, 121:1852–1853.

    Article  PubMed  CAS  Google Scholar 

  9. Massie BM, Shah NB: Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. Am Heart J 1997, 133:703–712.

    Article  PubMed  CAS  Google Scholar 

  10. Baigent C, Collins R, Appleby P, et al.: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither: The ISIS-2 (Second International Study of Infarct Survival) collaborative group. BMJ 1998, 316:1337–1343.

    PubMed  CAS  Google Scholar 

  11. Antiplatelet Trialists’ Collaboration: Collaborative overview of randomised trials of antiplatelet therapy-I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994, 308:81–106.

    Google Scholar 

  12. Sbarouni E, Bradshaw A, Andreotti F, et al.: Relationship between hemostatic abnormalities and neuroendocrine activity in heart failure. Am Heart J 1994, 127:607–612.

    Article  PubMed  CAS  Google Scholar 

  13. Goto S, Sakai H, Ikeda Y,et al.: Arterial thrombosis in heart failure (letter). Lancet 1998, 351:1558–1559.

    Article  PubMed  CAS  Google Scholar 

  14. Pitt B: Use of converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction. J Am Coll Cardiol 1993, 22(Suppl A):158A-161A.

    Article  PubMed  CAS  Google Scholar 

  15. Cleland JGF, Bulpitt CJ, Falk RH, et al.: Is aspirin safe for patients with heart failure? Br Heart J 1995, 74:215–219.

    PubMed  CAS  Google Scholar 

  16. Dzau VJ, Packer M, Lilly LS, et al.: Prostaglandins in severe congestive heart failure: relation to activation of the renninangiotensin system and hyponatremia. N Engl J Med 1984, 310:347–352.

    Article  PubMed  CAS  Google Scholar 

  17. Gainer JV, Morrow JD, Loveland A, et al.: Effect of bradykininreceptor blockade on the response to angiotensin-converting- enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998, 339:1285–1292.

    Article  PubMed  CAS  Google Scholar 

  18. Blais Jr. C, Drapeau G, Raymond P, et al.: Contribution of angiotensin-converting enzyme to the cardiac metabolism of bradykinin: an interspecies study. AM J Physiol 1997, 273:H2263-H2271.

    PubMed  CAS  Google Scholar 

  19. Swartz SL, Williams GH, Hollenberg NK, et al.: Captoprilinduced changes in prostaglandin production. J Clin Invest 1980, 65:1257–1264.

    Article  PubMed  CAS  Google Scholar 

  20. Moore TJ, Crantz FR, Hollenberg NK, et al.: Contribution of prostaglandins to the antihypertensive action of capropril in essential hypertension. Hypertension 1981, 3:168–173.

    PubMed  CAS  Google Scholar 

  21. Bhoola KD, Figueroa CD, Worthy K: Bioregulation of kinins: kallikerins, kininogens, and kinases. Pharmacol Rev 1992, 44:1–80.

    PubMed  CAS  Google Scholar 

  22. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature 1971, 231:232–235.

    CAS  Google Scholar 

  23. Jorde UP, Ennezat PV, Lisker J, et al.: Maximally recommended doses of angiotensin-converting enzyme (ACE) inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure. Circulation 2000, 101:844–846.

    PubMed  CAS  Google Scholar 

  24. Nishimura H, Kubo S, Ueyama M, et al.: Peripheral hemodynamic effects of captopril in patients with congestive heart failure. Am Heart J 1989, 117:100–105.

    Article  PubMed  CAS  Google Scholar 

  25. Townend JN, Doran J, Lote CJ, et al.: Peripheral hemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril. Br Heart J 1995, 73:434–441.

    PubMed  CAS  Google Scholar 

  26. Hall D, Zeitler H, Rudolph W: Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. Journal of the American College of Cardiology 1992, 20:1549–1555.

    Article  PubMed  CAS  Google Scholar 

  27. Nakamura M, Funakoshi T, Arakawa N, et al.: Effect of angiotensin-converting enzyme inhibitors on endotheliumdependent peripheral vasodilation in patients with chronic heart failure. J Am Coll Cardiol 1994, 24:1321–1327.

    Article  PubMed  CAS  Google Scholar 

  28. Spaulding C, Charbonnier B, Cohen-Solal A, et al.: Acute hemodynamic interaction of aspirin and ticlopidine with enalapril: results of a double-blind, randomized comparative trial. Circulation 1998, 98:757–765. An elegant study utilizing the differing mechanisms of antiplatelet action of aspirin and ticlopidine to demonstrate antagonism between aspirin and enalapril.

    PubMed  CAS  Google Scholar 

  29. Evans MA, Burnett JC, Redfield MM: Effect of low dose aspirin on cardiorenal function and acute hemodynamic response to enalaprilat in a canine model of severe heart failure. J Am Coll Cardiol 1995, 25:1445–1450.

    Article  PubMed  CAS  Google Scholar 

  30. van Wijngaarden J, Smit AJ, de Graeff PA, et al.: Effects of acetylsalicylic acid on peripheral hemodynamics in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 1994, 23:240–245.

    Article  PubMed  Google Scholar 

  31. Baur LHB, Schipperheyn JJ, van der Laarse A, et al.: Combining salicylate and enalapril in patients with coronary artery disease and heart failure. Br Heart J 1995, 73:227–236.

    PubMed  CAS  Google Scholar 

  32. Jeserich M, Pape L, Just H, et al.: Effect of long-term angiotensin- converting enzyme inhibition on vascular function in patients with chronic congestive heart failure. Am J Cardiol 1995, 76:1079–1082.

    Article  PubMed  CAS  Google Scholar 

  33. Clarke RJ, Mayo G, Price P, et al.: Suppression of thromboxane A2 but not systemic prostacyclin by controlled-release aspirin. N Engl J Med 1991, 325:1137–1141.

    Article  PubMed  CAS  Google Scholar 

  34. Oosterga M, Anthonio RL, de Kam P, et al.: Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction. Am J Cardiol 1998, 81:1178–1181.

    Article  PubMed  CAS  Google Scholar 

  35. Siegel JL, Miller A, Brown LK, et al.: Pulmonary diffusing capacity in left ventricular dysfunction. Chest 1990, 98:550–553.

    PubMed  CAS  Google Scholar 

  36. Puri S, Baker BL, Dutka DP, et al.: Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure: its pathophysiological relevance and relationship to exercise performance. Circulation 1995, 91:2769–2774.

    PubMed  CAS  Google Scholar 

  37. Guazzi M, Marenzi G, Alimento M, et al.: Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin. Circulation 1997, 95:1930–1936.

    PubMed  CAS  Google Scholar 

  38. Guazzi M, Melzi G, Agostoni P: Comparison of changes in respiratory function and exercise oxygen uptake with losartan versus enalapril in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1997, 80:1572–1576.

    Article  PubMed  CAS  Google Scholar 

  39. Guazzi M, Pontone G, Agostoni P: Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors. Am Heart J 1999, 138:254–260. This group from the Institute of Cardiology in Milan, Italy has extensively studied the effects of aspirin and ACE inhibitors on pulmonary function in patients with heart failure, demonstrating counteracting effects of aspirin on ACE inhibitor-induced improvements in pulmonary function and exercise performance.

    Article  PubMed  CAS  Google Scholar 

  40. Nguyen KN, Aursnes I, Kjekshus J: Interaction between enalapril and aspirin on mortality after acute myocardial infarction: subgroup analysis of the Cooperative New Scandinavian Enalapril Survival Study II. Am J Cardiol 1997, 79:115–119.

    Article  PubMed  CAS  Google Scholar 

  41. Peterson JG, Topol EJ, Sapp SK, et al.: Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease. Am J Med 2000, 109:371–377. The most recent study suggesting negative interaction between ACE inhibitors and aspirin in ischemic heart disease.

    Article  PubMed  CAS  Google Scholar 

  42. Garg R, Yusuf S: Overview of randomized trials of angiotensin- converting enzyme inhibitors on mortality and morbidity in patients with heart failure: Collaborative Group on ACE Inhibitor Trials. JAMA 1995, 273:1450–1456.

    Article  PubMed  CAS  Google Scholar 

  43. Leor J, Reicher-Reiss H, Goldbourt U, et al.: Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: a cohort study of 11,575 patients with coronary artery disease. J Am Coll Cardiol 1999, 33:1920–1925. A subgroup analysis of the BIP trial suggesting there may be synergy between ACE inhibitors and aspirin in the treatment of ischemic disease, both with and without heart failure.

    Article  PubMed  CAS  Google Scholar 

  44. Latini R, Santoro E, Masson S, et al. for the GISSI-3 Investigators: Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 trial. Heart Disease 2000, 2:185–190.

    PubMed  CAS  Google Scholar 

  45. Latini R, Tognoni G, Maggioni AP, et al. for the Angiotensinconverting Enzyme Inhibitor Myocardial Infarction Collaborative Group: Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. J Am Coll Cardiol 2000, 35:1801–1807. Very recent meta-analysis finding no significant antagonism between ACE inhibitor and aspirin therapy in the treatment of acute myocardial infarction.

    Article  PubMed  CAS  Google Scholar 

  46. Pitt B, Yusuf S, et al. for the Studies of Left Ventricular Dysfunction (SOLVD) Investigators: Studies of Left Ventricular Dysfunction (SOLVD): subgroup results. J Am Coll Cardiol 1992, 19(Suppl A):215A.

    Google Scholar 

  47. Al-khadra AS, Salem DN, Rand WM, et al.: Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial. J Am Coll Cardiol 1998, 31:419–425. The first major post hoc analysis of a large clinical trial in heart failure patients, suggesting a negative interaction with concomitant ACE inhibitor and antiplatelet administration (> 95% on aspirin).

    Article  PubMed  CAS  Google Scholar 

  48. Flather MD, Yusuf S, Kober L, et al. for the ACE-Inhibitor Myocardial Infarction Collaborative Group: Long-term ACEinhibitor therapy in patients with heart failure or leftventricular dysfunction: a systematic overview of data from individual patients. Lancet 2000, 355:1575–1581. Large meta-analysis of heart failure patients on chronic ACE inhibitor therapy demonstrating efficacy in reducing morbidity and mortality regardless of concomitant aspirin use.

    Article  PubMed  CAS  Google Scholar 

  49. Harjai KJ, Solis S, Prasad A, et al.: The use of aspirin in conjunction with angiotensin converting enzyme inhibitors does not worsen long-term survival in heart failure. Circulation 2000, 102(Suppl II):413.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moskowitz, R. The angiotensin-converting enzyme inhibitor and aspirin interaction in congestive heart failure:Fear or reality?. Curr Cardiol Rep 3, 247–253 (2001). https://doi.org/10.1007/s11886-001-0030-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-001-0030-0

Keywords

Navigation