Congestive heart failure ACE inhibitors
Editor(s)-In-Chief: James Chang, M.D., Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School [1] and C. Michael Gibson, M.S., M.D. [2], Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [3]
Overview
The Collaborative Group on ACE Inhibitor Trials demonstrated significant reduction in total mortality and hospitalization with the administration of ACEIs that was consistent among wide range of patients.[1]
ACE Inhibitors
Indications for an ACE Inhibitor or ARB
1. The left ventricular ejection fraction (LVEF) is ≤ 40%
or
2. There is a prior history of myocardial infarction (MI)
Background
- ACE-I or ARB therapy is recommended for ANY patient with reduced left ventricular ejection fraction (≤ 40%) regardless of the etiology of left ventricular systolic dysfunction (ischemic or nonischemic) or presence/absence of symptoms. Patients with or without heart failure (in other words, even those with asymptomatic left ventricular systolic dysfunction) are included in this recommendation.
- In addition, ACE-I/ARB therapy is indicated for patients with history of myocardial infarction whether or not left ventricular systolic dysfunction or heart failure is present.
- ACE-I or ARB therapy is also recommended for patients who are at high risk for the development of heart failure due to the presence of coronary, cerebrovascular, or peripheral vascular disease.
- Treatment should not be deferred in patients with few or no symptoms because of the significant mortality benefit derived from ACEI therapy.
Dosing
- ACE-I/ARB therapy should be initiated at low dosage such as 12.5 mg tid of captopril, 2.5 mg bid of enalapril[2][3], or 2.5 mg daily lisinopril.
- Every 4 to 6 weeks the dose is gradually uptitrated, as tolerated, toward target dosages of 20-40 mg daily for lisinopril, 10-20 mg twice daily for enalapril maleate, and 50-100 mg three times a day for captopril, or to the maximum tolerated dosage.
- ACE inhibitors are rarely adequate for the treatment of congestion without the use of diuretics.
Complications of ACE Inhibitors
- 5-10 % patients cannot tolerate ACE inhibitors because of cough. Cough can be a sign of elevated left-sided filling pressures or a side effect of ACE inhibitors due to excess bradykinin.
- ARBs are reserved for patients who are intolerant of ACE-Is for reasons (such as persistent cough) OTHER than hyperkalemia, progression of chronic kidney disease/worsening azotemia, or hypotension caused by prior ACE-I therapy. If a patient experiences hyperkalemia, worsening azotemia, or hypotension as a result of ACE-I therapy, the same is likely to result from ARB therapy. In the CHARM study candesartan reduced both hospitalization and mortality.[4][5]
- Renal artery stenosis should be considered if there's a decline in renal function with the initiation of ACE inhibitors.
2011 ACC/AHA Guidelines- Angiotensin-converting enzyme inhibitors [6][7]
| “ |
Class I1. Angiotensin-converting enzyme inhibitors (ACEIs) are recommended for all patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (LVEF), unless contraindicated.[8][1][9][10][11][12][13][14][15][16][3] (Level of Evidence: A) |
” |
Aldosterone Antagonists
Indications for Aldosterone Antagonists
A patient should be on an aldosterone antagonist if:
1. The potassium (K) is ≤ 5.0 mmol/liter
and
2. The creatinine (Cr) is ≤ 2.5 mg/dl
and
3. The left ventricular ejection fraction (LVEF) is ≤ 35%
OR
1. The potassium (K) is ≤ 5.0 mmol/liter
and
2. The creatinine (Cr) is ≤ 2.5 mg/dl
and
3. The left ventricular ejection fraction (LVEF is ≤ 40%[17]
and
4. There is a history of prior myocardial infarction (MI)
Background
- Aldosterone antagonists are, as the name suggests, receptor antagonists at the mineralocorticoid receptor. Antagonism of these receptors inhibits sodium resorption in the collecting duct of the nephron in the kidneys. This interferes with sodium/potassium exchange, reducing urinary potassium excretion and weakly increasing water excretion (diuresis). [18]
- Members of this class in clinical use include: Spironolactone[19]; Eplerenone[20][17] - more specific than spironolactone on target, but also more expensive; and Canrenone (canrenoate potassium)
- Aldosterone antagonist therapy is recommended for patients with advanced heart failure (NYHA class III or IV) and left ventricular systolic dysfunction (LVEF ≤ 35%), who are already receiving optimal medical therapy including loop diuretics, beta blockers and ACE-I/ARBs.
- In patients with diabetes mellitus or prior myocardial infarction, the LVEF below which this recommendation applies is 40%.
- In addition, the EMPHASIS-HF trial showed that eplerenone at a dose of 25-50mg daily reduced mortality and HF hospitalizations in patients with NYHA class I or II HF and should now be considered in these patients. This is not yet an AHA guideline but should be considered in this group of patients based on the available evidence.
Contraindications
- However, patients with baseline renal insufficiency (creatinine > 2.5 mg/dl or creatinine clearance < 30 ml/min), hyperkalemia (K > 5.0 mmol/liter), or who are unlikely to be available for frequent monitoring of renal function and electrolytes should NOT receive an aldosterone antagonist. Other potassium-sparing diuretics (such as triamterene) should not be administered concomitantly with an aldosterone antagonist.
Vote on and Suggest Revisions to the Current Guidelines
Guidelines Resources
- The ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult [6]
- 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation [7]
References
- ↑ 1.0 1.1 Garg R, Yusuf S (1995). "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 : the Journal of the American Medical Association. 273 (18): 1450–6. PMID 7654275. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ "Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators". The New England Journal of Medicine. 325 (5): 293–302. 1991. doi:10.1056/NEJM199108013250501. PMID 2057034. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 "Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group". The New England Journal of Medicine. 316 (23): 1429–35. 1987. doi:10.1056/NEJM198706043162301. PMID 2883575. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S (2003). "Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme". Lancet. 362 (9386): 759–66. PMID 13678868. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K (2004). "Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials". Circulation. 110 (17): 2618–26. doi:10.1161/01.CIR.0000146819.43235.A9. PMID 15492298. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ 6.0 6.1 Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American College of Chest Physicians; International Society for Heart and Lung Transplantation; Heart Rhythm Society. 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 Sep 20; 112(12): e154-235. Epub 2005 Sep 13. PMID 16160202
- ↑ 7.0 7.1 Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 119 (14):1977-2016. DOI:10.1161/CIRCULATIONAHA.109.192064 PMID: 19324967
- ↑ "A placebo-controlled trial of captopril in refractory chronic congestive heart failure. Captopril Multicenter Research Group". Journal of the American College of Cardiology. 2 (4): 755–63. 1983. PMID 6350401. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Sharpe DN, Murphy J, Coxon R, Hannan SF (1984). "Enalapril in patients with chronic heart failure: a placebo-controlled, randomized, double-blind study". Circulation. 70 (2): 271–8. PMID 6329547. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Chalmers JP, West MJ, Cyran J, De La Torre D, Englert M, Kramar M, Lewis GR, Maranhao MF, Myburgh DP, Schuster P (1987). "Placebo-controlled study of lisinopril in congestive heart failure: a multicentre study". Journal of Cardiovascular Pharmacology. 9 Suppl 3: S89–97. PMID 2442560.
|access-date=requires|url=(help) - ↑ Cleland JG, Dargie HJ, Hodsman GP, Ball SG, Robertson JI, Morton JJ, East BW, Robertson I, Murray GD, Gillen G (1984). "Captopril in heart failure. A double blind controlled trial". British Heart Journal. 52 (5): 530–5. PMC 481676. PMID 6388612. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Cleland JG, Dargie HJ, Ball SG, Gillen G, Hodsman GP, Morton JJ, East BW, Robertson I, Ford I, Robertson JI (1985). "Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state". British Heart Journal. 54 (3): 305–12. PMC 481900. PMID 2994698. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Cowley AJ, Rowley JM, Stainer KL, Hampton JR (1982). "Captopril therapy for heart failure. A placebo controlled study". Lancet. 2 (8301): 730–2. PMID 6125809. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Bayliss J, Norell MS, Canepa-Anson R, Reid C, Poole-Wilson P, Sutton G (1985). "Clinical importance of the renin-angiotensin system in chronic heart failure: double blind comparison of captopril and prazosin". British Medical Journal (Clinical Research Ed.). 290 (6485): 1861–5. PMC 1416765. PMID 3924285. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Drexler H, Banhardt U, Meinertz T, Wollschläger H, Lehmann M, Just H (1989). "Contrasting peripheral short-term and long-term effects of converting enzyme inhibition in patients with congestive heart failure. A double-blind, placebo-controlled trial". Circulation. 79 (3): 491–502. PMID 2521816. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ Erhardt L, MacLean A, Ilgenfritz J, Gelperin K, Blumenthal M (1995). "Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group". European Heart Journal. 16 (12): 1892–9. PMID 8682023. Retrieved 2012-04-05. Unknown parameter
|month=ignored (help) - ↑ 17.0 17.1 Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B (2011). "Eplerenone in patients with systolic heart failure and mild symptoms". The New England Journal of Medicine. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. PMID 21073363. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
- ↑ Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999). "The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators". The New England Journal of Medicine. 341 (10): 709–17. doi:10.1056/NEJM199909023411001. PMID 10471456. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help) - ↑ Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M (2003). "Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction". The New England Journal of Medicine. 348 (14): 1309–21. doi:10.1056/NEJMoa030207. PMID 12668699. Retrieved 2012-04-03. Unknown parameter
|month=ignored (help)