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Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist

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Abstract

The presence of heart failure or left ventricular systolic dysfunction in the setting of acute myocardial infarction is associated with poor prognosis. Aldosterone is an important downstream mediator of the reninangiotensin-aldosterone system that promotes myocardial collagen deposition, myocardial fibrosis, apoptosis, ventricular remodeling, and endothelial dysfunction. It may play an important role in the increased morbidity and mortality and the development and progression of heart failure after acute myocardial infarction. Extending the findings from the Randomized Aldactone Evaluation Study (RALES) in patients with chronic heart failure, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone offered a significant survival benefit, attenuation of progression of heart failure, and prevention of sudden cardiac death when used in addition to optimal medical therapy. The current evidence-based guidelines now suggest that aldosterone blockade should be an integral component of heart failure therapy to improve outcomes in this high-risk population.

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References and Recommended Reading

  1. 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). Circulation 2004, 110:588–636.

    Article  PubMed  Google Scholar 

  2. Guidry UC, Evans JC, Larson MG, et al.: Temporal trends in event rates after Q-wave myocardial infarction: the Framingham Heart Study. Circulation 1999, 100:2054–2059.

    PubMed  CAS  Google Scholar 

  3. Haber E: George C. Griffith lecture. The role of renin in normal and pathological cardiovascular homeostasis. Circulation 1976, 54;849–861.

    PubMed  CAS  Google Scholar 

  4. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  5. Pitt B, Remme W, Zannad F, et al.; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321. [Published correction appears in N Engl J Med 2003, 348:2271.]

    Article  PubMed  CAS  Google Scholar 

  6. Weber KT, Sun Y: Recruitable ACE and tissue repair in the infarcted heart. J Renin Angiotensin Aldosterone Syst 2000, 1:295–303.

    Article  PubMed  CAS  Google Scholar 

  7. Weber KT, Brilla CG, Campbell SE, et al.: Myocardial fibrosis: role of angiotensin II and aldosterone. Basic Res Cardiol 1993, 88(Suppl 1)107–124.

    PubMed  CAS  Google Scholar 

  8. Hunt SA, Abraham WT, Chin MH, et al.: ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: 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 2005, 112:e154–e235.

    Article  PubMed  Google Scholar 

  9. Swedberg K, Cleland J, Dargie H, et al.: Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 2005, 26:1115–1140.

    Article  PubMed  CAS  Google Scholar 

  10. Struthers AD: Aldosterone blockade in cardiovascular disease. Heart 2004, 90:1229–1234.

    Article  PubMed  Google Scholar 

  11. Lal A, Veinot JP, Ganten D, Leenen FH: Prevention of cardiac remodeling after myocardial infarction in transgenic rats deficient in brain angiotensinogen. J Mol Cell Cardiol 2005, 39:521–529.

    Article  PubMed  CAS  Google Scholar 

  12. Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA: Controversies in ventricular remodelling. Lancet 2006, 367:356–367.

    Article  PubMed  Google Scholar 

  13. Delcayre C, Silvestre JS, Garnier A, et al.: Cardiac aldosterone production and ventricular remodeling. Kidney Int 2000, 57:1346–1351.

    Article  PubMed  CAS  Google Scholar 

  14. Silvestre JS, Heymes C, Oubenaissa A, et al.: Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation 1999, 99:2694–2701.

    PubMed  CAS  Google Scholar 

  15. Hayashi M, Tsutamoto T, Wada A, et al.: Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction. J Am Coll Cardiol 2001, 38:1375–1382.

    Article  PubMed  CAS  Google Scholar 

  16. Hein S, Arnon E, Kostin S, et al.: Progression from compensated hypertrophy to failure in the pressure-overloaded human heart. Structural deterioration and compensatory mechanisms. Circulation 2003, 107:984–991.

    Article  PubMed  Google Scholar 

  17. Modena MG, Aventa P, Menozzi PM, Rossi R: Aldosterone inhibition limits collagen synthesis and progressive left ventricular enlargement after anterior myocardial infarction. Am Heart J 2001, 141:41–46.

    Article  PubMed  CAS  Google Scholar 

  18. Poulsen SH, Host NB, Jensen SE, Egstrup K: Relationship between serum amino-terminal propeptide of type III procollagen and changes of left ventricular function after acute myocardial infarction. Circulation 2000, 101:1527–1532.

    PubMed  CAS  Google Scholar 

  19. Zannad F, Alla F, Dousset B, et al.: Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure. Circulation 2000, 102:2700–2706.

    PubMed  CAS  Google Scholar 

  20. Katada J, Meguro T, Saito H, et al.: Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptorknockout mice after myocardial infarction. Circulation 2005, 111:2157–2164.

    Article  PubMed  CAS  Google Scholar 

  21. Staessen J, Lijnen P, Fagard R, et al.: Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol 1981, 91:457–465.

    PubMed  CAS  Google Scholar 

  22. Borghi C, Boschi S, Ambrosioni E, et al.: Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol 1993, 33:40–45.

    PubMed  CAS  Google Scholar 

  23. 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. [Published correction appears in J Am Coll Cardiol 2002, 39:746].

    Article  PubMed  CAS  Google Scholar 

  24. Tang WH, Parameswaran AC, Maroo AP, Francis GS: Aldosterone receptor antagonists in the medical management of chronic heart failure. Mayo Clin Proc 2005, 80:1623–1630.

    Article  PubMed  CAS  Google Scholar 

  25. Bauersachs J, Heck M, Fraccarollo D, et al.: Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol 2002, 39:351–358.

    Article  PubMed  CAS  Google Scholar 

  26. Farquharson CA, Struthers AD: Spironolactone increases nitric oxide bioactivity, improves endothelial vasodilator dysfunction, and suppresses vascular angiotensin I/angiotensin II conversion in patients with chronic heart failure. Circulation 2000, 101:594–597.

    PubMed  CAS  Google Scholar 

  27. Barr CS, Lang CC, Hanson J, et al.: Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease. Am J Cardiol 1995, 76:1259–1265.

    Article  PubMed  CAS  Google Scholar 

  28. Dyckner T, Wester PO, Widman L: Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. Eur J Clin Pharmacol 1986, 30:535–540.

    Article  PubMed  CAS  Google Scholar 

  29. Pitt B, Pitt GS: Added benefit of mineralocorticoid receptor blockade in the primary prevention of sudden cardiac death. Circulation 2007, 115:2976–2982.

    Article  PubMed  Google Scholar 

  30. Cohn JN, Colucci W: Cardiovascular effects of aldosterone and post-acute myocardial infarction pathophysiology. Am J Cardiol 2006, 97(Suppl):4F–12F.

    Article  PubMed  CAS  Google Scholar 

  31. Pitt B, White H, Nicolau J, et al.: Eplerenone reduces mortality 30 days postrandomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005, 46:425–431.

    Article  PubMed  CAS  Google Scholar 

  32. 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 

  33. Banas J, White H, Parkhomenko A, et al.: Favorable outcomes with 25 mg of eplerenone in patients with post-AMI heart failure: results from the EPHESUS trial. J Card Fail 2005, 11(6 Suppl):S156.

    Google Scholar 

  34. Pitt B, Ferrari R, Gheorghiade M, et al.: Aldosterone blockade in post-acute myocardial infarction heart failure. Clin Cardiol 2006, 29:434–438.

    Article  PubMed  Google Scholar 

  35. Weintraub WS, Zhang Z, Mahoney EM, et al.: Cost-effectiveness of eplerenone compared with placebo in patients with myocardial infarction complicated by left ventricular dysfunction and heart failure. Circulation 2005, 111:1106–1113.

    Article  PubMed  Google Scholar 

  36. Hohnloser SH, Kuck KH, Dorian P, et al.: Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004, 351:2481–2488.

    Article  PubMed  CAS  Google Scholar 

  37. Juurlink DN, Mamdani MM, Lee DS, et al.: Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004, 351:543–551.

    Article  PubMed  CAS  Google Scholar 

  38. Levey AS, Bosch JP, Lewis JB, et al.: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 1999, 130:461–447.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Noninvasive Cardiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Scott D. Solomon

  2. Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Scott D. Solomon

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  1. Anil Verma
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  2. Scott D. Solomon
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Correspondence to Scott D. Solomon.

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Verma, A., Solomon, S.D. Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist. Curr Heart Fail Rep 4, 183–189 (2007). https://doi.org/10.1007/s11897-007-0011-8

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  • DOI: https://doi.org/10.1007/s11897-007-0011-8

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