Skip to main content
SpringerLink
Log in

Inhibiting the renin-angiotensin system with ACE inhibitors or ARBs after MI

  • Published:
Current Heart Failure Reports Aims and scope Submit manuscript

Abstract

As part of the recommended modern post-myocardial infarction (MI) management, including reperfusion strategies, antiplatelet therapy, and β-blockers, we may wonder whether the impact of early inhibition of the renin-angiotensin system (RAS) is as important as it was 20 years ago. This review demonstrates that significant clinical benefit can be derived from angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) even when added to other currently recommended treatment strategies in post-MI patients. Moreover, the effects of RAS inhibition extend far beyond the early post-MI neurohormonal activation and left ventricular remodeling phases. The favorable effects of RAS inhibition on important prognostic markers such as atrial fibrillation, renal function, and diabetes have recently been unraveled. Post-MI RAS inhibition also benefits all age groups, including elderly patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Pfeffer JM, Pfeffer MA, Braunwald E: Hemodynamic benefits and prolonged survival with long-term captopril therapy in rats with myocardial infarction and heart failure. Circulation 1987, 75:I149–I155.

    PubMed  CAS  Google Scholar 

  2. Pfeffer JM, Pfeffer MA, Fletcher PJ, et al.: Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol 1991, 260:H1406–H1414.

    PubMed  CAS  Google Scholar 

  3. Pfeffer MA, Braunwald E: Ventricular enlargement following infarction is a modifiable process. Am J Cardiol 1991, 68:127D–131D.

    Article  PubMed  CAS  Google Scholar 

  4. Pfeffer MA, Braunwald E, Moye LA, et al.: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992, 327:669–677.

    Article  PubMed  CAS  Google Scholar 

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

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Antman EM, Anbe DT, Armstrong PW, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol 2004, 44:671–719.

    Article  PubMed  Google Scholar 

  8. Sharpe N, Murphy J, Smith H, et al.: Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet 1988, 1(8580):255–259.

    Article  PubMed  CAS  Google Scholar 

  9. Lax CJ, Domenighetti AA, Pavia JM, et al.: Transitory reduction in angiotensin AT2 receptor expression levels in postinfarct remodelling in rat myocardium. Clin Exp Pharmacol Physiol 2004, 31:512–517.

    Article  PubMed  CAS  Google Scholar 

  10. Schmieder R, Hilgers K, Schlaich MP, et al.: Reninangiotensin system and cardiovascular risk. Lancet 2007, 369:1208–1219.

    Article  PubMed  CAS  Google Scholar 

  11. Adachi Y, Saito Y, Kishimoto I, et al.: Angiotensin II type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice. Circulation 2003, 107:2406–2408.

    Article  PubMed  CAS  Google Scholar 

  12. Yang Z, Bove CM, French BA, et al.: Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction. Circulation 2002, 106:106–111.

    Article  PubMed  CAS  Google Scholar 

  13. Takai S, Jin D, Sakaguchi M, Miyazaki M: Chymase-dependent angiotensin II formation in human vascular tissue. Circulation 1999, 100:654–658.

    PubMed  CAS  Google Scholar 

  14. Chrysant SG, Chrysant GS: The pleiotropic effects of angiotensin receptor blockers. J Clin Hypertens 2006, 8:261–268.

    Article  CAS  Google Scholar 

  15. Cohn JN, Ferrari R, Sharpe N, et al.: Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol 2000, 35:569–582.

    Article  PubMed  CAS  Google Scholar 

  16. Pfeffer MA, Braunwald E: Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation 1990, 81:1161–1172.

    PubMed  CAS  Google Scholar 

  17. St John Sutton M, Pfeffer MA, Plappert T, et al.: Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril. Circulation 1994, 89:68–75.

    PubMed  CAS  Google Scholar 

  18. Pfeffer MA: Left ventricular remodeling after acute myocardial infarction. Annu Rev Med 1995, 46:455–466.

    Article  PubMed  CAS  Google Scholar 

  19. Savoye C, Equine O, Tricot O, et al.: Left ventricular remodeling after anterior wall myocardial infarction in modern clinical practice (from the REmodelage VEntriculaire [REVE] Study Group). Am J Cardiol 2006, 98:1144–1149.

    Article  PubMed  Google Scholar 

  20. Abdulla J, Barlera S, Latini R, et al.: A systematic review: effect of angiotensin converting enzyme inhibition on left ventricular volumes and ejection fraction in patients with a myocardial infarction and in patients with left ventricular dysfunction. Eur Heart J 2007, 9:129–135.

    Article  CAS  Google Scholar 

  21. Pfeffer MA, McMurray JJ, Velazquez EJ, et al.: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003, 349:1893–1906.

    Article  PubMed  CAS  Google Scholar 

  22. Solomon SD, Skali H, Anavekar NS, et al.: Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction. Circulation 2005, 111:3411–3419.

    Article  PubMed  CAS  Google Scholar 

  23. Flather MD, Yusuf S, Kober L, et al.: Long-term ACE-inhibitor therapy in patients with heart failure or leftventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000, 355:1575–1581.

    Article  PubMed  CAS  Google Scholar 

  24. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987, 316:1429–1435.

  25. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991, 325:293–302.

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

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

    Article  PubMed  CAS  Google Scholar 

  28. Swedberg K, Held P, Kjekshus J, et al.: Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 1992, 327:678–684.

    Article  PubMed  CAS  Google Scholar 

  29. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico. Lancet 1994, 343:1115–1122.

  30. ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet 1995, 345:669–685.

  31. Oral captopril versus placebo among 14,962 patients with suspected acute myocardial infarction: a multicenter, randomized, double-blind, placebo controlled clinical trial. Chinese Cardiac Study (CCS-1) Collaborative Group. Chin Med J (Engl) 1997, 110:834–838.

  32. Ambrosioni E, Borghi C, Magnani B: The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. N Engl J Med 1995, 332:80–85.

    Article  PubMed  CAS  Google Scholar 

  33. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group. Circulation 1998, 97:2202–2212.

  34. Mielniczuk L, Stevenson LW: Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers in the management of congestive heart failure patients: what have we learned from recent clinical trials? Curr Opin Cardiol 2005, 20:250–255.

    Article  PubMed  Google Scholar 

  35. Yusuf S, Sleight P, Pogue J: Effects of an angiotensinconverting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:145–153.

    Article  PubMed  CAS  Google Scholar 

  36. Fox KM: Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003, 362:782–788.

    Article  PubMed  CAS  Google Scholar 

  37. Braunwald E, Antman EM, Beasley JW: ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002, 106:1893–1900.

    Article  PubMed  Google Scholar 

  38. Petrie MC, Padmanabhan N, McDonald JE, et al.: Angiotensin converting enzyme (ACE) and non-ACE dependent angiotensin II generation in resistance arteries from patients with heart failure and coronary heart disease. J Am Coll Cardiol 2001, 37:1056–1061.

    Article  PubMed  CAS  Google Scholar 

  39. Mankad S, d’Amato TA, Reichek N, et al.: Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling. Circulation 2001, 103:2845–2850.

    PubMed  CAS  Google Scholar 

  40. Yu CM, Tipoe GL, Wing-Hon LK, et al.: Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction. J Am Coll Cardiol 2001, 38:1207–1215.

    Article  PubMed  CAS  Google Scholar 

  41. Konstam MA, Patten RD: Antagonism of the reninangiotensin system in heart failure. In Heart Failure: A Companion to Braunwald’s Heart Disease. Edited by Mann DJ. Philadelphia: Saunders; 2004:603–618.

    Google Scholar 

  42. Dickstein K, Kjekshus J; OPTIMAAL Steering Committee of the OPTIMAAL Study Group: Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002, 360:752–760.

    Article  PubMed  CAS  Google Scholar 

  43. Cohn JN, Tognoni G: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001, 345:1667–1675.

    Article  PubMed  CAS  Google Scholar 

  44. McMurray JJ, Ostergren J, Swedberg K, et al.: Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003, 362:767–771.

    Article  PubMed  CAS  Google Scholar 

  45. Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321.

    Article  PubMed  CAS  Google Scholar 

  46. Matsubara H: Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res 1998, 83:1182–1191.

    PubMed  CAS  Google Scholar 

  47. Strauss MH, Hall AS: Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARBMI paradox. Circulation 2006, 114:838–854.

    Article  PubMed  Google Scholar 

  48. Yamada T, Horiuchi M, Dzau VJ: Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A 1996, 93:156–160.

    Article  PubMed  CAS  Google Scholar 

  49. Kim MP, Zhou M, Wahl LM: Angiotensin II increases human monocyte matrix metalloproteinase-1 through the AT2 receptor and prostaglandin E2: implications for atherosclerotic plaque rupture. J Leukoc Biol 2005, 78:195–201.

    Article  PubMed  CAS  Google Scholar 

  50. Teo K, Yusuf S, Sleight P, et al.: Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004, 148:52–61.

    Article  PubMed  CAS  Google Scholar 

  51. Domanski MJ, Exner DV, Borkowf CB, et al.: Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol 1999, 33:598–604.

    Article  PubMed  CAS  Google Scholar 

  52. Solomon SD, Zelenkofske S, McMurray JJV, et al.: Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. N Engl J Med 2005, 352:2581–2588.

    Article  PubMed  CAS  Google Scholar 

  53. Mäkikallio TH, Barthel P, Schneider R, et al.: Frequency of sudden cardiac death among acute myocardial infarction survivors with optimized medical and revascularization therapy. Am J Cardiol 2006, 97:480–484.

    Article  PubMed  Google Scholar 

  54. Pedersen OD, Bagger H, Kober L, Torp-Pedersen C: The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TR Andolapril Cardiac Evaluation. Eur Heart J 1999, 20:748–754.

    Article  PubMed  CAS  Google Scholar 

  55. Pedersen OD, Bagger H, Kober L, et al.: Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation 1999, 100:376–380.

    PubMed  CAS  Google Scholar 

  56. Patlolla V, Alsheikh-Ali AA, Al-Ahmad AM: The reninangiotensin system: a therapeutic target in atrial fibrillation. Pacing Clin Electrophysiol 2006, 29:1006–1012.

    Article  PubMed  Google Scholar 

  57. Anavekar NS, McMurray JJV, Velazquez EJ, et al.: Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004, 351:1285–1295.

    Article  PubMed  CAS  Google Scholar 

  58. Tokmakova MP, Skali H, Kenchaiah S, et al.: Chronic kidney disease, cardiovascular risk, and response to angiotensin-converting enzyme inhibition after myocardial infarction: the Survival And Ventricular Enlargement (SAVE) study. Circulation 2004, 110:3667–3673.

    Article  PubMed  CAS  Google Scholar 

  59. Windt WAKM, Eijkelkamp WBA, Henning RH, et al.: Renal damage after myocardial infarction is prevented by renin-angiotensin-aldosterone system intervention. J Am Soc Nephrol 2006, 17:3059–3066.

    Article  PubMed  CAS  Google Scholar 

  60. Jose P, Tomson C, Skali H, et al.: Influence of proteinuria on cardiovascular risk and response to angiotensin-converting enzyme inhibition after myocardial infarction. J Am Coll Cardiol 2006, 47:1725–1727.

    Article  PubMed  Google Scholar 

  61. Aguilar D, Solomon SD, Kober L, et al.: Newly diagnosed and previously known diabetes mellitus and 1-year outcomes of acute myocardial infarction: the VAL sartan In Acute myocardial iNfarcTion (VALIANT) trial. Circulation 2004, 110:1572–1578.

    Article  PubMed  Google Scholar 

  62. Abdulla J, Pogue J, Abildstrom SZ, et al.: Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction—a meta-analysis. Eur J Heart Fail 2006, 8:90–96.

    Article  PubMed  CAS  Google Scholar 

  63. O’Meara E, Solomon S, McMurray J, et al.: 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 2004, 25:1920–1926.

    Article  PubMed  CAS  Google Scholar 

  64. Gold LD, Krumholz HM. Gender differences in treatment of heart failure and acute myocardial infarction: a question of quality or epidemiology? Cardiol Rev 2006, 14:180–186.

    Article  PubMed  Google Scholar 

  65. White HD, Aylward PE, Huang Z, et al.: Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Circulation 2005, 112:3391–3399.

    Article  PubMed  CAS  Google Scholar 

  66. Ferrari R; Perindopril and Remodeling in Elderly with Acute Myocardial Infarction Investigators: Effects of angiotensin-converting enzyme inhibition with perindopril on left ventricular remodeling and clinical outcome: results of the randomized Perindopril and Remodeling in Elderly with Acute Myocardial Infarction (PREAMI) Study. Arch Intern Med 2006, 166:659–666.

    Article  PubMed  CAS  Google Scholar 

  67. Alexander KP, Newby LK, Armstrong PW, et al.: Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007, 115:2570–2589.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Montreal Heart Institute (Université de Montréal), 5000 Belanger, Montreal, QC, H1T 1C8, Canada

    Eileen O’Meara

Authors
  1. Maryse Palardy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anique Ducharme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eileen O’Meara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eileen O’Meara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Palardy, M., Ducharme, A. & O’Meara, E. Inhibiting the renin-angiotensin system with ACE inhibitors or ARBs after MI. Curr Heart Fail Rep 4, 190–197 (2007). https://doi.org/10.1007/s11897-007-0012-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11897-007-0012-7

Keywords

Search

Navigation