Congestive heart failure ACE inhibitors: Difference between revisions

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__NOTOC__
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| [[File:Siren.gif|30px|link= Congestive heart failure resident survival guide]]|| <br> || <br>
| [[Acute decompensated heart failure resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{| class="infobox" style="float:right;"
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| [[File:Critical_Pathways.gif|88px|link= Congestive heart failure critical pathways]]|| <br> || <br>
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{{Congestive heart failure}}
{{Congestive heart failure}}


'''Editor(s)-In-Chief:''' James Chang, M.D., Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School [mailto:jchang@caregroup.org] and [[User:C Michael Gibson|C. Michael Gibson, M.S., M.D.]] [mailto:mgibson@perfuse.org], Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School
'''Editor(s)-In-Chief:''' James Chang, M.D., Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School [mailto:jchang@caregroup.org] and [[User:C Michael Gibson|C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com], Cardiovascular Division Beth Israel Deaconess Medical Center, Boston MA, Harvard Medical School; {{AOEIC}} {{LG}};{{MehdiP}} {{EdzelCo}}


==Overview==
==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.<ref name="pmid7654275">{{cite journal |author=Garg R, Yusuf S |title=Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials |journal=[[JAMA : the Journal of the American Medical Association]] |volume=273 |issue=18 |pages=1450–6 |year=1995 |month=May |pmid=7654275 |doi= |url= |accessdate=2012-04-03}}</ref>
==ACE Inhibitors==
===Indications for ACE Inhibitors Use===


==Indications for an ACE Inhibitor or ARB==
1. The [[left ventricular ejection fraction]] ([[LVEF]]) is ≤ 40%
1. The [[left ventricular ejection fraction]] ([[LVEF]]) is ≤ 40%


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2. There is a prior history of [[myocardial infarction]] ([[MI]])
2. There is a prior history of [[myocardial infarction]] ([[MI]])


==Background==
===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.
*[[ACE inhibitor|ACE-I]] or [[Angiotensin II receptor antagonist|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.
*In addition, [[ACE inhibitor|ACE-I]] or [[Angiotensin II receptor antagonist|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.
*[[ACE inhibitor|ACE-I]] or [[Angiotensin II receptor antagonist|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 [[Angiotensin converting enzyme inhibitor|ACEI]] therapy.
* Treatment should not be deferred in patients with few or no symptoms because of the significant mortality benefit derived from [[Angiotensin converting enzyme inhibitor|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]], 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==
===Dosing===
* [[ACE inhibitor|ACE-I]] or [[Angiotensin II receptor antagonist|ARB]] therapy should be initiated at low dosage such as 12.5 mg tid of [[captopril]], 2.5 mg bid of [[enalapril]]<ref name="pmid2057034">{{cite journal |author= |title=Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators |journal=[[The New England Journal of Medicine]] |volume=325 |issue=5 |pages=293–302 |year=1991 |month=August |pmid=2057034 |doi=10.1056/NEJM199108013250501 |url=http://dx.doi.org/10.1056/NEJM199108013250501 |accessdate=2012-04-03}}</ref><ref name="pmid2883575">{{cite journal |author= |title=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 |journal=[[The New England Journal of Medicine]] |volume=316 |issue=23 |pages=1429–35 |year=1987 |month=June |pmid=2883575 |doi=10.1056/NEJM198706043162301 |url=http://www.nejm.org/doi/abs/10.1056/NEJM198706043162301?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed |accessdate=2012-04-03}}</ref>, 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|enalapril maleate]], and 50-100 mg three times a day for [[captopril]], or to the maximum tolerated dosage.
* [[ACEIs|ACE inhibitors]] are rarely adequate for the treatment of congestion without the use of [[diuretics]].
 
==Complications==
* 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]].  
* 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.
*[[Angiotensin II receptor antagonist|ARBs]] are reserved for patients who are intolerant of [[ACEIs|ACE-Is]] for reasons (such as persistent cough) '''''OTHER''''' than [[hyperkalemia]], progression of chronic kidney disease/worsening [[azotemia]], or [[hypotension]] caused by prior [[ACEIs|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 [[Angiotensin II receptor antagonist|ARB therapy]]. In the CHARM study [[candesartan]] reduced both hospitalization and mortality.<ref name="pmid13678868">{{cite journal |author=Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S |title=Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme |journal=[[Lancet]] |volume=362 |issue=9386 |pages=759–66 |year=2003 |month=September |pmid=13678868 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673603142821 |accessdate=2012-04-03}}</ref><ref name="pmid15492298">{{cite journal |author=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 |title=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 |journal=[[Circulation]] |volume=110 |issue=17 |pages=2618–26 |year=2004 |month=October |pmid=15492298 |doi=10.1161/01.CIR.0000146819.43235.A9 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15492298 |accessdate=2012-04-03}}</ref>
* [[Renal artery stenosis]] should be considered if there's a decline in renal function with the initiation of [[ACE inhibitors]].
* [[Renal artery stenosis]] should be considered if there's a decline in renal function with the initiation of [[ACE inhibitors]].


==Indications for Aldosterone Antagonists==
==2022 AHA/ ACC/ HFSA Heart Failure Guideline/ 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America ((DO NOT EDIT) <ref name="pmid35363500">{{cite journal| author=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM | display-authors=etal| title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. | journal=Circulation | year= 2022 | volume= 145 | issue= 18 | pages= e876-e894 | pmid=35363500 | doi=10.1161/CIR.0000000000001062 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=35363500  }} </ref><ref name="pmid23747642">{{cite journal| author=Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE et al.| title=2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=J Am Coll Cardiol | year= 2013 | volume=  | issue=  | pages=  | pmid=23747642 | doi=10.1016/j.jacc.2013.05.019 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23747642  }} </ref><ref name="pmid19324967">Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19324967 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.[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192064 DOI:10.1161/CIRCULATIONAHA.109.192064] PMID: [http://pubmed.gov/19324967 19324967]</ref>==
A patient should be on an aldosterone antagonist if:


1. The potassium (K) is ≤ 5.0 mmol/liter
====[[Renin-Angiotensin System]] Inhibition With [[ACEi]] or [[ARB]] or [[ARNi]]====
'''''and'''''
2. The creatinine (Cr) is ≤ 2.5 mg/dl
'''''and'''''
3. The [[left ventricular ejection fraction]] ([[LVEF]]) is ≤ 35%


'''''OR'''''
{|class="wikitable" style="width:80%"
|-
| colspan="1" style="text-align:center; background:LightGreen"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]


1. The potassium (K) is ≤  5.0 mmol/liter
|-
'''''and'''''
|bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' In [[patients]] with [[HFrEF]] and [[NYHA]] class II to III [[symptoms]], the use of [[ARNi]] is recommended to reduce [[morbidity]] and [[mortality]]. <ref name="pmid25176015">{{cite journal| author=McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR | display-authors=etal| title=Angiotensin-neprilysin inhibition versus enalapril in heart failure. | journal=N Engl J Med | year= 2014 | volume= 371 | issue= 11 | pages= 993-1004 | pmid=25176015 | doi=10.1056/NEJMoa1409077 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25176015  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25659916 Review in: Evid Based Med. 2015 Apr;20(2):61]  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25686189 Review in: Ann Intern Med. 2015 Feb 17;162(4):JC2] </ref><ref name="pmid31134724">{{cite journal| author=Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z | display-authors=etal| title=Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. | journal=Eur J Heart Fail | year= 2019 | volume= 21 | issue= 8 | pages= 998-1007 | pmid=31134724 | doi=10.1002/ejhf.1498 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31134724  }} </ref><ref name="pmid30415601">{{cite journal| author=Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K | display-authors=etal| title=Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. | journal=N Engl J Med | year= 2019 | volume= 380 | issue= 6 | pages= 539-548 | pmid=30415601 | doi=10.1056/NEJMoa1812851 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30415601  }} </ref><ref name="pmid31475296">{{cite journal| author=Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J | display-authors=etal| title=Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. | journal=JAMA | year= 2019 | volume= 322 | issue= 11 | pages= 1077-1084 | pmid=31475296 | doi=10.1001/jama.2019.12843 | pmc=6749534 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31475296  }} </ref><ref name="pmid31240976">{{cite journal| author=Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D| title=Effects of the Angiotensin-Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta-Analysis. | journal=J Am Heart Assoc | year= 2019 | volume= 8 | issue= 13 | pages= e012272 | pmid=31240976 | doi=10.1161/JAHA.119.012272 | pmc=6662364 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31240976  }} </ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
2. The creatinine (Cr) is ≤ 2.5 mg/dl
'''''and'''''
3. The [[left ventricular ejection fraction]] ([[LVEF]] is ≤ 40%
'''''and'''''
4. There is a history of prior [[myocardial infarction]] ([[MI]])


|-
|bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' In [[patients]] with previous or current [[symptoms]] of [[chronic]] [[HFrEF]], the use of [[ACEi]] is beneficial to reduce [[morbidity]] and [[mortality]] when the use of [[ARNi]] is not feasible.<ref name="pmid2883575">{{cite journal| author=CONSENSUS Trial Study Group| title=Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). | journal=N Engl J Med | year= 1987 | volume= 316 | issue= 23 | pages= 1429-35 | pmid=2883575 | doi=10.1056/NEJM198706043162301 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2883575  }} </ref><ref name="pmid2057034">{{cite journal| author=SOLVD Investigators. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN| title=Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. | journal=N Engl J Med | year= 1991 | volume= 325 | issue= 5 | pages= 293-302 | pmid=2057034 | doi=10.1056/NEJM199108013250501 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2057034  }} </ref><ref name="pmid10587334">{{cite journal| author=Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM | display-authors=etal| title=Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. | journal=Circulation | year= 1999 | volume= 100 | issue= 23 | pages= 2312-8 | pmid=10587334 | doi=10.1161/01.cir.100.23.2312 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10587334  }} </ref><ref name="pmid1386652">{{cite journal| author=Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE | display-authors=etal| title=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. | journal=N Engl J Med | year= 1992 | volume= 327 | issue= 10 | pages= 669-77 | pmid=1386652 | doi=10.1056/NEJM199209033271001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1386652  }} </ref><ref name="pmid8104270">{{cite journal| author=| title=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. | journal=Lancet | year= 1993 | volume= 342 | issue= 8875 | pages= 821-8 | pmid=8104270 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8104270  }} </ref><ref name="pmid7477219">{{cite journal| author=Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K | display-authors=etal| title=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. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 25 | pages= 1670-6 | pmid=7477219 | doi=10.1056/NEJM199512213332503 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7477219  }} </ref><ref name="pmid7654275">{{cite journal| author=Garg R, Yusuf S| title=Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. | journal=JAMA | year= 1995 | volume= 273 | issue= 18 | pages= 1450-6 | pmid=7654275 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7654275  }} </ref><ref name="pmid20625347">{{cite journal| author=Woodard-Grice AV, Lucisano AC, Byrd JB, Stone ER, Simmons WH, Brown NJ| title=Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema. | journal=Pharmacogenet Genomics | year= 2010 | volume= 20 | issue= 9 | pages= 532-6 | pmid=20625347 | doi=10.1097/FPC.0b013e32833d3acb | pmc=2945219 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20625347  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>


==Background==
|-
|bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' In [[patients]] with previous or current [[symptoms]] of [[chronic]] [[HFrEF]] who are intolerant to [[ACEi]] because of [[cough]] or [[angioedema]] and when the use of [[ARNi]] is not feasible, the use of [[ARB]] is recommended to reduce [[morbidity]] and [[mortality]]. <ref name="pmid11759645">{{cite journal| author=Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators| title=A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. | journal=N Engl J Med | year= 2001 | volume= 345 | issue= 23 | pages= 1667-75 | pmid=11759645 | doi=10.1056/NEJMoa010713 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11759645  }} </ref><ref name="pmid14610160">{{cite journal| author=Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP | display-authors=etal| title=Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 20 | pages= 1893-906 | pmid=14610160 | doi=10.1056/NEJMoa032292 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14610160  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=15230551 Review in: ACP J Club. 2004 Jul-Aug;141(1):3] </ref><ref name="pmid19922995">{{cite journal| author=Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA | display-authors=etal| title=Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. | journal=Lancet | year= 2009 | volume= 374 | issue= 9704 | pages= 1840-8 | pmid=19922995 | doi=10.1016/S0140-6736(09)61913-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19922995  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=20436124 Review in: Evid Based Med. 2010 Apr;15(2):51-2] </ref><ref name="pmid18700309">{{cite journal| author=Dominiak M| title=[Commentary to the article: ONTARGET Investigators, Yusuf S, Teo KK, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-59]. | journal=Kardiol Pol | year= 2008 | volume= 66 | issue= 6 | pages= 705-6; discussion 707 | pmid=18700309 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18700309  }} </ref><ref name="pmid18757085">{{cite journal| author=Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Yusuf S, Teo K, Anderson C, Pogue J, Dyal L | display-authors=etal| title=Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. | journal=Lancet | year= 2008 | volume= 372 | issue= 9644 | pages= 1174-83 | pmid=18757085 | doi=10.1016/S0140-6736(08)61242-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18757085  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=19238604 Review in: Ann Intern Med. 2009 Feb 17;150(4):JC2-6] </ref>  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>


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%. 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.
|-
|bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' In [[patients]] with [[chronic]] [[symptomatic]] [[HFrEF]] [[NYHA]] class II or III who tolerate an [[ACEi]] or [[ARB]], replacement by an [[ARNi]] is recommended to further reduce [[morbidity]] and [[mortality]].  <ref name="pmid25176015">{{cite journal| author=McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR | display-authors=etal| title=Angiotensin-neprilysin inhibition versus enalapril in heart failure. | journal=N Engl J Med | year= 2014 | volume= 371 | issue= 11 | pages= 993-1004 | pmid=25176015 | doi=10.1056/NEJMoa1409077 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25176015  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25659916 Review in: Evid Based Med. 2015 Apr;20(2):61]  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=25686189 Review in: Ann Intern Med. 2015 Feb 17;162(4):JC2] </ref><ref name="pmid31134724">{{cite journal| author=Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z | display-authors=etal| title=Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study. | journal=Eur J Heart Fail | year= 2019 | volume= 21 | issue= 8 | pages= 998-1007 | pmid=31134724 | doi=10.1002/ejhf.1498 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31134724  }} </ref><ref name="pmid30415601">{{cite journal| author=Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K | display-authors=etal| title=Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. | journal=N Engl J Med | year= 2019 | volume= 380 | issue= 6 | pages= 539-548 | pmid=30415601 | doi=10.1056/NEJMoa1812851 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30415601  }} </ref><ref name="pmid31475296">{{cite journal| author=Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J | display-authors=etal| title=Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. | journal=JAMA | year= 2019 | volume= 322 | issue= 11 | pages= 1077-1084 | pmid=31475296 | doi=10.1001/jama.2019.12843 | pmc=6749534 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31475296  }} </ref><ref name="pmid31240976">{{cite journal| author=Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D| title=Effects of the Angiotensin-Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta-Analysis. | journal=J Am Heart Assoc | year= 2019 | volume= 8 | issue= 13 | pages= e012272 | pmid=31240976 | doi=10.1161/JAHA.119.012272 | pmc=6662364 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31240976  }} </ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>


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.
|}
* [[Spironolactone]] is third line therapy for CHF
 
* An important side effect of spironolactone is [[hyperkalemia]]
{|class="wikitable" style="width:80%"
|-
| colspan="1" style="text-align:center; background:"White"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class Value Statement: High Value]]
 
|-
|bgcolor="White"|<nowiki>"</nowiki>'''4.''' In [[patients]] with previous or current [[symptoms]] of [[chronic]] [[HFrEF]], in whom [[ARNi]] is not feasible, [[treatment]] with an [[ACEi]] or [[ARB]] provides high economic value. <ref name="pmid23433562">{{cite journal| author=Banka G, Heidenreich PA, Fonarow GC| title=Incremental cost-effectiveness of guideline-directed medical therapies for heart failure. | journal=J Am Coll Cardiol | year= 2013 | volume= 61 | issue= 13 | pages= 1440-6 | pmid=23433562 | doi=10.1016/j.jacc.2012.12.022 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23433562  }} </ref><ref name="pmid10516413">{{cite journal| author=Dasbach EJ, Rich MW, Segal R, Gerth WC, Carides GW, Cook JR | display-authors=etal| title=The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure. | journal=Cardiology | year= 1999 | volume= 91 | issue= 3 | pages= 189-94 | pmid=10516413 | doi=10.1159/000006908 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10516413  }} </ref><ref name="pmid12836712">{{cite journal| author=Glick H, Cook J, Kinosian B, Pitt B, Bourassa MG, Pouleur H | display-authors=etal| title=Costs and effects of enalapril therapy in patients with symptomatic heart failure: an economic analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial. | journal=J Card Fail | year= 1995 | volume= 1 | issue= 5 | pages= 371-80 | pmid=12836712 | doi=10.1016/s1071-9164(05)80006-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12836712  }} </ref><ref name="pmid8185426">{{cite journal| author=Paul SD, Kuntz KM, Eagle KA, Weinstein MC| title=Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure. | journal=Arch Intern Med | year= 1994 | volume= 154 | issue= 10 | pages= 1143-9 | pmid=8185426 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8185426  }} </ref><ref name="pmid15215801">{{cite journal| author=Reed SD, Friedman JY, Velazquez EJ, Gnanasakthy A, Califf RM, Schulman KA| title=Multinational economic evaluation of valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT). | journal=Am Heart J | year= 2004 | volume= 148 | issue= 1 | pages= 122-8 | pmid=15215801 | doi=10.1016/j.ahj.2003.12.040 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15215801  }} </ref><ref name="pmid14571595">{{cite journal| author=Shekelle P, Morton S, Atkinson S, Suttorp M, Tu W, Heidenreich P | display-authors=etal| title=Pharmacologic management of heart failure and left ventricular systolic dysfunction: effect in female, black, and diabetic patients, and cost-effectiveness. | journal=Evid Rep Technol Assess (Summ) | year= 2003 | volume=  | issue= 82 | pages= 1-6 | pmid=14571595 | doi= | pmc=4781559 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14571595  }} </ref><ref name="pmid7560617">{{cite journal| author=Tsevat J, Duke D, Goldman L, Pfeffer MA, Lamas GA, Soukup JR | display-authors=etal| title=Cost-effectiveness of captopril therapy after myocardial infarction. | journal=J Am Coll Cardiol | year= 1995 | volume= 26 | issue= 4 | pages= 914-9 | pmid=7560617 | doi=10.1016/0735-1097(95)00284-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7560617  }} </ref>''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
 
|-
|bgcolor="White"|<nowiki>"</nowiki>'''6.''' In [[patients]] with [[chronic]] [[symptomatic]] [[HFrEF]], [[treatment]] with an [[ARNi]] instead of an [[ACEi]] provides high economic value. <ref name="pmid27438344">{{cite journal| author=Gaziano TA, Fonarow GC, Claggett B, Chan WW, Deschaseaux-Voinet C, Turner SJ | display-authors=etal| title=Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction. | journal=JAMA Cardiol | year= 2016 | volume= 1 | issue= 6 | pages= 666-72 | pmid=27438344 | doi=10.1001/jamacardio.2016.1747 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27438344  }} </ref><ref name="pmid32785628">{{cite journal| author=Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD| title=Cost-effectiveness of Sacubitril-Valsartan in Hospitalized Patients Who Have Heart Failure With Reduced Ejection Fraction. | journal=JAMA Cardiol | year= 2020 | volume= 5 | issue= 11 | pages= 1236-1244 | pmid=32785628 | doi=10.1001/jamacardio.2020.2822 | pmc=7675099 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32785628  }} </ref><ref name="pmid27039128">{{cite journal| author=King JB, Shah RU, Bress AP, Nelson RE, Bellows BK| title=Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction. | journal=JACC Heart Fail | year= 2016 | volume= 4 | issue= 5 | pages= 392-402 | pmid=27039128 | doi=10.1016/j.jchf.2016.02.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27039128  }} </ref><ref name="pmid27571284">{{cite journal| author=Sandhu AT, Ollendorf DA, Chapman RH, Pearson SD, Heidenreich PA| title=Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction. | journal=Ann Intern Med | year= 2016 | volume= 165 | issue= 10 | pages= 681-689 | pmid=27571284 | doi=10.7326/M16-0057 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27571284  }} </ref>  ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
 
|}
 
{|class="wikitable" style="width:80%"
|-
|colspan="1" style="text-align:center; background:LightCoral"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (Harm)
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''7.''' [[ARNi]] should not be administered concomitantly with [[ACEi]] or within 36 hours of the last [[dose]] of an [[ACEi]]. <ref name="pmid12186794">{{cite journal| author=Packer M, Califf RM, Konstam MA, Krum H, McMurray JJ, Rouleau JL | display-authors=etal| title=Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE). | journal=Circulation | year= 2002 | volume= 106 | issue= 8 | pages= 920-6 | pmid=12186794 | doi=10.1161/01.cir.0000029801.86489.50 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12186794  }} </ref><ref name="pmid14751650">{{cite journal| author=Kostis JB, Packer M, Black HR, Schmieder R, Henry D, Levy E| title=Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial. | journal=Am J Hypertens | year= 2004 | volume= 17 | issue= 2 | pages= 103-11 | pmid=14751650 | doi=10.1016/j.amjhyper.2003.09.014 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14751650  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B-R]])'' <nowiki>"</nowiki>
 
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''8.''' [[ARNi]] should not be administered to [[patients]] with any [[history]] of [[angioedema]].<ref name="pmid25306450">{{cite journal| author=Vardeny O, Miller R, Solomon SD| title=Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure. | journal=JACC Heart Fail | year= 2014 | volume= 2 | issue= 6 | pages= 663-70 | pmid=25306450 | doi=10.1016/j.jchf.2014.09.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25306450  }} </ref><ref name="pmid10968427">{{cite journal| author=Messerli FH, Nussberger J| title=Vasopeptidase inhibition and angio-oedema. | journal=Lancet | year= 2000 | volume= 356 | issue= 9230 | pages= 608-9 | pmid=10968427 | doi=10.1016/S0140-6736(00)02596-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10968427  }} </ref><ref name="pmid25766951">{{cite journal| author=Braunwald E| title=The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure. | journal=J Am Coll Cardiol | year= 2015 | volume= 65 | issue= 10 | pages= 1029-41 | pmid=25766951 | doi=10.1016/j.jacc.2015.01.033 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25766951  }} </ref><ref name="pmid20236700">{{cite journal| author=Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP| title=Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study. | journal=Lancet | year= 2010 | volume= 375 | issue= 9722 | pages= 1255-66 | pmid=20236700 | doi=10.1016/S0140-6736(09)61966-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20236700  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C-LD]])'' <nowiki>"</nowiki>
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''9.''' [[ACEi]] should not be administered to [[patients]] with any [[history]] of [[angioedema]]. <ref name="pmid17085287">{{cite journal| author=Byrd JB, Adam A, Brown NJ| title=Angiotensin-converting enzyme inhibitor-associated angioedema. | journal=Immunol Allergy Clin North Am | year= 2006 | volume= 26 | issue= 4 | pages= 725-37 | pmid=17085287 | doi=10.1016/j.iac.2006.08.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17085287  }} </ref><ref name="pmid23147456">{{cite journal| author=Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF | display-authors=etal| title=Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. | journal=Arch Intern Med | year= 2012 | volume= 172 | issue= 20 | pages= 1582-9 | pmid=23147456 | doi=10.1001/2013.jamainternmed.34 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23147456  }}  [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=&cmd=prlinks&id=23635842 Review in: Evid Based Med. 2013 Dec;18(6):e52] </ref><ref name="pmid22521308">{{cite journal| author=Makani H, Messerli FH, Romero J, Wever-Pinzon O, Korniyenko A, Berrios RS | display-authors=etal| title=Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. | journal=Am J Cardiol | year= 2012 | volume= 110 | issue= 3 | pages= 383-91 | pmid=22521308 | doi=10.1016/j.amjcard.2012.03.034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22521308  }} </ref><ref name="pmid30618189">{{cite journal| author=Rasmussen ER, Pottegård A, Bygum A, von Buchwald C, Homøe P, Hallas J| title=Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study. | journal=J Intern Med | year= 2019 | volume= 285 | issue= 5 | pages= 553-561 | pmid=30618189 | doi=10.1111/joim.12867 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30618189  }} </ref> ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C-LD]])'' <nowiki>"</nowiki>
 
|}
 
==Vote on and Suggest Revisions to the Current Guidelines==
*[[The Living Guidelines: Diagnosis and Management of Chronic Heart Failure | The CHF Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines]]
 
==External Links==
*[https://www.ahajournals.org/doi/epub/10.1161/CIR.0000000000001063.full.pdf 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines]<ref name="pmid35363499">{{cite journal |vauthors=Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW |title=2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines |journal=Circulation |volume=145 |issue=18 |pages=e895–e1032 |date=May 2022 |pmid=35363499 |doi=10.1161/CIR.0000000000001063 |url=}} </ref>
 
*[http://circ.ahajournals.org/content/112/12/e154.full.pdf The ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult] <ref name="Hunt"> 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</ref>
 
*[http://content.onlinejacc.org/cgi/reprint/53/15/1343.pdf 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] <ref name="pmid19324967">Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG et al. (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19324967 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. [http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192064 DOI:10.1161/CIRCULATIONAHA.109.192064] PMID: [http://pubmed.gov/19324967 19324967]</ref>


==References==
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Latest revision as of 20:59, 22 June 2022
Resident
Survival
Guide
File:Critical Pathways.gif

Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

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Treatment

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Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
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Hydralazine
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Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure ACE inhibitors On the Web

Most recent articles

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Ongoing Trials at Clinical Trials.gov

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Congestive heart failure ACE inhibitors in the news

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Directions to Hospitals Treating Congestive heart failure ACE inhibitors

Risk calculators and risk factors for 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];Seyedmahdi Pahlavani, M.D. [4] Edzel Lorraine Co, DMD, MD[5]

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 ACE Inhibitors Use

1. The left ventricular ejection fraction (LVEF) is ≤ 40%

or

2. There is a prior history of myocardial infarction (MI)

Background

Dosing

  • ACE-I or 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

2022 AHA/ ACC/ HFSA Heart Failure Guideline/ 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America ((DO NOT EDIT) [6][7][8]

Renin-Angiotensin System Inhibition With ACEi or ARB or ARNi

Class I
"1. In patients with HFrEF and NYHA class II to III symptoms, the use of ARNi is recommended to reduce morbidity and mortality. [9][10][11][12][13](Level of Evidence: A) "
"2. In patients with previous or current symptoms of chronic HFrEF, the use of ACEi is beneficial to reduce morbidity and mortality when the use of ARNi is not feasible.[3][2][14][15][16][17][1][18] (Level of Evidence: A) "
"3. In patients with previous or current symptoms of chronic HFrEF who are intolerant to ACEi because of cough or angioedema and when the use of ARNi is not feasible, the use of ARB is recommended to reduce morbidity and mortality. [19][20][21][22][23] (Level of Evidence: A) "
"5. In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACEi or ARB, replacement by an ARNi is recommended to further reduce morbidity and mortality. [9][10][11][12][13](Level of Evidence: B-R) "
Class Value Statement: High Value
"4. In patients with previous or current symptoms of chronic HFrEF, in whom ARNi is not feasible, treatment with an ACEi or ARB provides high economic value. [24][25][26][27][28][29][30](Level of Evidence: A) "
"6. In patients with chronic symptomatic HFrEF, treatment with an ARNi instead of an ACEi provides high economic value. [31][32][33][34] (Level of Evidence: A) "
Class III (Harm)
"7. ARNi should not be administered concomitantly with ACEi or within 36 hours of the last dose of an ACEi. [35][36] (Level of Evidence: B-R) "
"8. ARNi should not be administered to patients with any history of angioedema.[37][38][39][40] (Level of Evidence: C-LD) "
"9. ACEi should not be administered to patients with any history of angioedema. [41][42][43][44] (Level of Evidence: C-LD) "

Vote on and Suggest Revisions to the Current Guidelines

External Links

References

  1. ↑ 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)
  2. ↑ 2.0 2.1 "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. ↑ 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)
  4. ↑ 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)
  5. ↑ 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. ↑ Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM; et al. (2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e876–e894. doi:10.1161/CIR.0000000000001062. PMID 35363500 Check |pmid= value (help).
  7. ↑ Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE; et al. (2013). "2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. doi:10.1016/j.jacc.2013.05.019. PMID 23747642.
  8. ↑ 8.0 8.1 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
  9. ↑ 9.0 9.1 McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR; et al. (2014). "Angiotensin-neprilysin inhibition versus enalapril in heart failure". N Engl J Med. 371 (11): 993–1004. doi:10.1056/NEJMoa1409077. PMID 25176015. Review in: Evid Based Med. 2015 Apr;20(2):61 Review in: Ann Intern Med. 2015 Feb 17;162(4):JC2
  10. ↑ 10.0 10.1 Wachter R, Senni M, Belohlavek J, Straburzynska-Migaj E, Witte KK, Kobalava Z; et al. (2019). "Initiation of sacubitril/valsartan in haemodynamically stabilised heart failure patients in hospital or early after discharge: primary results of the randomised TRANSITION study". Eur J Heart Fail. 21 (8): 998–1007. doi:10.1002/ejhf.1498. PMID 31134724.
  11. ↑ 11.0 11.1 Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K; et al. (2019). "Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure". N Engl J Med. 380 (6): 539–548. doi:10.1056/NEJMoa1812851. PMID 30415601.
  12. ↑ 12.0 12.1 Desai AS, Solomon SD, Shah AM, Claggett BL, Fang JC, Izzo J; et al. (2019). "Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial". JAMA. 322 (11): 1077–1084. doi:10.1001/jama.2019.12843. PMC 6749534 Check |pmc= value (help). PMID 31475296.
  13. ↑ 13.0 13.1 Wang Y, Zhou R, Lu C, Chen Q, Xu T, Li D (2019). "Effects of the Angiotensin-Receptor Neprilysin Inhibitor on Cardiac Reverse Remodeling: Meta-Analysis". J Am Heart Assoc. 8 (13): e012272. doi:10.1161/JAHA.119.012272. PMC 6662364 Check |pmc= value (help). PMID 31240976.
  14. ↑ Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM; et al. (1999). "Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group". Circulation. 100 (23): 2312–8. doi:10.1161/01.cir.100.23.2312. PMID 10587334.
  15. ↑ Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE; et al. (1992). "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. 327 (10): 669–77. doi:10.1056/NEJM199209033271001. PMID 1386652.
  16. ↑ "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. 342 (8875): 821–8. 1993. PMID 8104270.
  17. ↑ Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K; et al. (1995). "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. 333 (25): 1670–6. doi:10.1056/NEJM199512213332503. PMID 7477219.
  18. ↑ Woodard-Grice AV, Lucisano AC, Byrd JB, Stone ER, Simmons WH, Brown NJ (2010). "Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema". Pharmacogenet Genomics. 20 (9): 532–6. doi:10.1097/FPC.0b013e32833d3acb. PMC 2945219. PMID 20625347.
  19. ↑ Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators (2001). "A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure". N Engl J Med. 345 (23): 1667–75. doi:10.1056/NEJMoa010713. PMID 11759645.
  20. ↑ Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP; et al. (2003). "Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both". N Engl J Med. 349 (20): 1893–906. doi:10.1056/NEJMoa032292. PMID 14610160. Review in: ACP J Club. 2004 Jul-Aug;141(1):3
  21. ↑ Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA; et al. (2009). "Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial". Lancet. 374 (9704): 1840–8. doi:10.1016/S0140-6736(09)61913-9. PMID 19922995. Review in: Evid Based Med. 2010 Apr;15(2):51-2
  22. ↑ Dominiak M (2008). "[Commentary to the article: ONTARGET Investigators, Yusuf S, Teo KK, Pogue J et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547-59]". Kardiol Pol. 66 (6): 705–6, discussion 707. PMID 18700309.
  23. ↑ Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Yusuf S, Teo K, Anderson C, Pogue J, Dyal L; et al. (2008). "Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial". Lancet. 372 (9644): 1174–83. doi:10.1016/S0140-6736(08)61242-8. PMID 18757085. Review in: Ann Intern Med. 2009 Feb 17;150(4):JC2-6
  24. ↑ Banka G, Heidenreich PA, Fonarow GC (2013). "Incremental cost-effectiveness of guideline-directed medical therapies for heart failure". J Am Coll Cardiol. 61 (13): 1440–6. doi:10.1016/j.jacc.2012.12.022. PMID 23433562.
  25. ↑ Dasbach EJ, Rich MW, Segal R, Gerth WC, Carides GW, Cook JR; et al. (1999). "The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure". Cardiology. 91 (3): 189–94. doi:10.1159/000006908. PMID 10516413.
  26. ↑ Glick H, Cook J, Kinosian B, Pitt B, Bourassa MG, Pouleur H; et al. (1995). "Costs and effects of enalapril therapy in patients with symptomatic heart failure: an economic analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial". J Card Fail. 1 (5): 371–80. doi:10.1016/s1071-9164(05)80006-5. PMID 12836712.
  27. ↑ Paul SD, Kuntz KM, Eagle KA, Weinstein MC (1994). "Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure". Arch Intern Med. 154 (10): 1143–9. PMID 8185426.
  28. ↑ Reed SD, Friedman JY, Velazquez EJ, Gnanasakthy A, Califf RM, Schulman KA (2004). "Multinational economic evaluation of valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial (Val-HeFT)". Am Heart J. 148 (1): 122–8. doi:10.1016/j.ahj.2003.12.040. PMID 15215801.
  29. ↑ Shekelle P, Morton S, Atkinson S, Suttorp M, Tu W, Heidenreich P; et al. (2003). "Pharmacologic management of heart failure and left ventricular systolic dysfunction: effect in female, black, and diabetic patients, and cost-effectiveness". Evid Rep Technol Assess (Summ) (82): 1–6. PMC 4781559. PMID 14571595.
  30. ↑ Tsevat J, Duke D, Goldman L, Pfeffer MA, Lamas GA, Soukup JR; et al. (1995). "Cost-effectiveness of captopril therapy after myocardial infarction". J Am Coll Cardiol. 26 (4): 914–9. doi:10.1016/0735-1097(95)00284-1. PMID 7560617.
  31. ↑ Gaziano TA, Fonarow GC, Claggett B, Chan WW, Deschaseaux-Voinet C, Turner SJ; et al. (2016). "Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction". JAMA Cardiol. 1 (6): 666–72. doi:10.1001/jamacardio.2016.1747. PMID 27438344.
  32. ↑ Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD (2020). "Cost-effectiveness of Sacubitril-Valsartan in Hospitalized Patients Who Have Heart Failure With Reduced Ejection Fraction". JAMA Cardiol. 5 (11): 1236–1244. doi:10.1001/jamacardio.2020.2822. PMC 7675099 Check |pmc= value (help). PMID 32785628 Check |pmid= value (help).
  33. ↑ King JB, Shah RU, Bress AP, Nelson RE, Bellows BK (2016). "Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction". JACC Heart Fail. 4 (5): 392–402. doi:10.1016/j.jchf.2016.02.007. PMID 27039128.
  34. ↑ Sandhu AT, Ollendorf DA, Chapman RH, Pearson SD, Heidenreich PA (2016). "Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction". Ann Intern Med. 165 (10): 681–689. doi:10.7326/M16-0057. PMID 27571284.
  35. ↑ Packer M, Califf RM, Konstam MA, Krum H, McMurray JJ, Rouleau JL; et al. (2002). "Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE)". Circulation. 106 (8): 920–6. doi:10.1161/01.cir.0000029801.86489.50. PMID 12186794.
  36. ↑ Kostis JB, Packer M, Black HR, Schmieder R, Henry D, Levy E (2004). "Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial". Am J Hypertens. 17 (2): 103–11. doi:10.1016/j.amjhyper.2003.09.014. PMID 14751650.
  37. ↑ Vardeny O, Miller R, Solomon SD (2014). "Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure". JACC Heart Fail. 2 (6): 663–70. doi:10.1016/j.jchf.2014.09.001. PMID 25306450.
  38. ↑ Messerli FH, Nussberger J (2000). "Vasopeptidase inhibition and angio-oedema". Lancet. 356 (9230): 608–9. doi:10.1016/S0140-6736(00)02596-4. PMID 10968427.
  39. ↑ Braunwald E (2015). "The path to an angiotensin receptor antagonist-neprilysin inhibitor in the treatment of heart failure". J Am Coll Cardiol. 65 (10): 1029–41. doi:10.1016/j.jacc.2015.01.033. PMID 25766951.
  40. ↑ Ruilope LM, Dukat A, Böhm M, Lacourcière Y, Gong J, Lefkowitz MP (2010). "Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study". Lancet. 375 (9722): 1255–66. doi:10.1016/S0140-6736(09)61966-8. PMID 20236700.
  41. ↑ Byrd JB, Adam A, Brown NJ (2006). "Angiotensin-converting enzyme inhibitor-associated angioedema". Immunol Allergy Clin North Am. 26 (4): 725–37. doi:10.1016/j.iac.2006.08.001. PMID 17085287.
  42. ↑ Toh S, Reichman ME, Houstoun M, Ross Southworth M, Ding X, Hernandez AF; et al. (2012). "Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system". Arch Intern Med. 172 (20): 1582–9. doi:10.1001/2013.jamainternmed.34. PMID 23147456. Review in: Evid Based Med. 2013 Dec;18(6):e52
  43. ↑ Makani H, Messerli FH, Romero J, Wever-Pinzon O, Korniyenko A, Berrios RS; et al. (2012). "Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors". Am J Cardiol. 110 (3): 383–91. doi:10.1016/j.amjcard.2012.03.034. PMID 22521308.
  44. ↑ Rasmussen ER, Pottegård A, Bygum A, von Buchwald C, Homøe P, Hallas J (2019). "Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study". J Intern Med. 285 (5): 553–561. doi:10.1111/joim.12867. PMID 30618189.
  45. ↑ Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW (May 2022). "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 145 (18): e895–e1032. doi:10.1161/CIR.0000000000001063. PMID 35363499 Check |pmid= value (help).
  46. ↑ 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

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