Editing Heart failure (section)

====Medication====
Quadruple medical therapy using a combination of [[sacubitril/valsartan|angiotensin receptor-neprilysin inhibitors (ARNI)]], [[beta blocker]]s, [[Antimineralocorticoid|mineralocorticoid receptor antagonists (MRA)]], and [[SGLT2 inhibitor|sodium/glucose cotransporter 2 inhibitors (SGLT2 inhibitors)]] is the standard of care as of 2021 for heart failure with reduced ejection fraction (HFrEF).<ref>{{cite journal | vauthors= Greene S, Khan M, et al. |title=Quadruple Medical Therapy for Heart Failure |journal = J Am Coll Cardiol |date= March 2021 |volume= 77 |issue=11 |pages=1408–1411  |doi=10.1016/j.jacc.2021.02.006 |pmid=33736822 |s2cid=232299815 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Straw S, McGinlay M, Witte KK  |title= Four pillars of heart failure: contemporary pharmacological therapy for heart failure with reduced ejection fraction |journal=[[Open Heart (journal)|Open Heart]] |date= 2021  |volume= 8 |issue= 1 |page=e001585 |doi= 10.1136/openhrt-2021-001585|pmid= 33653703 |pmc= 7929859 }}</ref>

There is no convincing evidence for pharmacological treatment of heart failure with preserved ejection fraction (HFpEF).<ref name="ESC2021">{{cite journal | vauthors = McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JG, Coats AJ, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CS, Lyon AR, McMurray JJ, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GM, Ruschitzka F, Kathrine Skibelund A | title = 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure | journal = European Heart Journal | volume = 42 | issue = 36 | pages = 3599–3726 | date = September 2021 | pmid = 34447992 | doi = 10.1093/eurheartj/ehab368 | url = https://academic.oup.com/eurheartj/article-pdf/42/36/3599/40594787/ehab368.pdf | access-date = 7 February 2023 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20220908043625/https://academic.oup.com/eurheartj/article-pdf/42/36/3599/40594787/ehab368.pdf | archive-date = 8 September 2022 }}</ref> Medication for HFpEF is symptomatic treatment with diuretics to treat congestion.<ref name="ESC2021"/> Managing risk factors and comorbidities such as [[hypertension]] is recommended in HFpEF.<ref name="ESC2021"/>

Inhibitors of the [[renin–angiotensin system]] (RAS) are recommended for heart failure. The [[sacubitril/valsartan|angiotensin receptor-neprilysin inhibitors (ARNI) sacubitril/valsartan]] is recommended as the first choice of RAS inhibitors in American guidelines published by AHA/ACC in 2022.<ref name="AHA2022"/> Use of [[ACE inhibitor]], or [[angiotensin receptor blockers]] (ARBs) if the person develops a long-term cough as a side effect of the ACE-I,<ref>{{cite book | vauthors = Goljan EF |title=Rapid Review Pathology |edition = 4th |location=Philadelphia, PA |publisher=Saunders/Elsevier |date=2014 |isbn=978-0-323-08787-2 }}</ref> is associated with improved survival, fewer hospitalizations for heart failure exacerbations, and improved quality of life in people with heart failure.<ref name=NICECG108>{{NICE|108|Chronic heart failure – managements (ARBs) of chronic heart failure in adults in primary and secondary care | August 2010}}</ref> European guidelines published by ESC in 2021 recommends that [[sacubitril/valsartan|ARNI]] should be used in those who still have symptoms while on an [[ACE inhibitor|ACE-I]] or [[angiotensin receptor blocker|ARB]], [[beta blocker]], and a [[mineralocorticoid receptor antagonist]]. Use of the combination agent ARNI requires the cessation of ACE-I or ARB therapy at least 36 hours before its initiation.<ref name="AHA2022"/>

[[Beta blockers|Beta-adrenergic blocking agents (beta blockers)]] add to the improvement in symptoms and [[Case fatality rate|mortality]] provided by ACE-I/ARB.<ref name=NICECG108 /><ref>{{cite journal | vauthors = Kotecha D, Manzano L, Krum H, Rosano G, Holmes J, Altman DG, Collins PD, Packer M, Wikstrand J, Coats AJ, Cleland JG, Kirchhof P, von Lueder TG, Rigby AS, Andersson B, Lip GY, van Veldhuisen DJ, Shibata MC, Wedel H, Böhm M, Flather MD | title = Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis | journal = BMJ | volume = 353 | pages = i1855 | date = April 2016 | pmid = 27098105 | pmc = 4849174 | doi = 10.1136/bmj.i1855 }}</ref> The mortality benefits of beta blockers in people with systolic dysfunction who also have [[atrial fibrillation]] is more limited than in those who do not have it.<ref name="Kotecha 2014">{{cite journal | vauthors = Kotecha D, Holmes J, Krum H, Altman DG, Manzano L, Cleland JG, Lip GY, Coats AJ, Andersson B, Kirchhof P, von Lueder TG, Wedel H, Rosano G, Shibata MC, Rigby A, Flather MD | title = Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis | journal = Lancet | volume = 384 | issue = 9961 | pages = 2235–43 | date = December 2014 | pmid = 25193873 | doi = 10.1016/S0140-6736(14)61373-8 | s2cid = 25660815 | url = http://pure-oai.bham.ac.uk/ws/files/21568198/Kotecha_et_al_Lancet_Efficacy_of_beta_blockers_The_Lancet_2014_Post_Print.pdf | access-date = 27 May 2019 | archive-date = 28 September 2020 | archive-url = https://web.archive.org/web/20200928221341/http://pure-oai.bham.ac.uk/ws/files/21568198/Kotecha_et_al_Lancet_Efficacy_of_beta_blockers_The_Lancet_2014_Post_Print.pdf | url-status = live }}</ref> If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed, but reduction in hospital admission for uncontrolled symptoms has not been observed.<ref>{{cite journal | vauthors = Liu F, Chen Y, Feng X, Teng Z, Yuan Y, Bin J | title = Effects of beta-blockers on heart failure with preserved ejection fraction: a meta-analysis | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e90555 | date = 5 March 2014 | pmid = 24599093 | pmc = 3944014 | doi = 10.1371/journal.pone.0090555 | bibcode = 2014PLoSO...990555L | doi-access = free }}</ref>

In people who are intolerant of ACE-I and ARB or who have significant kidney dysfunction, the use of combined [[hydralazine]] and a long-acting nitrate, such as [[isosorbide dinitrate]], is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure.<ref name="NatClinGuide CHF">{{cite book | chapter = Chapter 5: Treating heart failure | title = Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care | edition = Partial Update [Internet]. | author = National Clinical Guideline Centre (UK) | publisher = Royal College of Physicians | location = London (UK) | date = August 2010 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK65330/ | access-date = 31 August 2017 | archive-date = 6 September 2017 | archive-url = https://web.archive.org/web/20170906120901/https://www.ncbi.nlm.nih.gov/books/NBK65330/ | url-status = live }}</ref> It is especially beneficial in the black population.{{efn|Specifically, in one randomized control trial the patients self-identified as black (defined as of African descent), and in one randomized control trial the patients were defined as ''black'', without further details given.<ref name="NatClinGuide CHF" />}}<ref name="NatClinGuide CHF" />

Use of a [[mineralocorticoid antagonist]], such as [[spironolactone]] or [[eplerenone]], in addition to beta blockers and ACE-I, can improve symptoms and reduce mortality in people with symptomatic heart failure with reduced ejection fraction (HFrEF).<ref name="NICE2018ch6"/>

[[SGLT2 inhibitor]]s are used for heart failure with reduced ejection fraction as they have demonstrated benefits in reducing hospitalizations and mortality, regardless of whether an individual has comorbid Type 2 Diabetes or not.<ref name="AHA2022">{{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 = Journal of the American College of Cardiology | volume = 79 | issue = 17 | pages = e263–e421 | date = May 2022 | pmid = 35379503 | doi = 10.1016/j.jacc.2021.12.012 | s2cid = 247882156 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, Packer M | title = SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials | journal = Lancet | volume = 396 | issue = 10254 | pages = 819–829 | date = September 2020 | pmid = 32877652 | doi = 10.1016/S0140-6736(20)31824-9 }}</ref>

=====Other medications=====
Second-line medications for CHF do not confer a mortality benefit. [[Digoxin]] is one such medication. Its narrow therapeutic window, a high degree of toxicity, and the failure of multiple trials to show a mortality benefit have reduced its role in clinical practice. It is now used in only a small number of people with refractory symptoms, who are in atrial fibrillation, and/or who have chronic hypotension.<ref>{{cite web| url=https://www.lecturio.com/concepts/congestive-heart-failure/| title=Congestive Heart Failure| website=The Lecturio Medical Concept Library| date=7 August 2020| access-date=10 July 2021| archive-date=10 July 2021| archive-url=https://web.archive.org/web/20210710035402/https://www.lecturio.com/concepts/congestive-heart-failure/| url-status=live}}</ref><ref>{{cite web|title=Digoxin|url=https://www.drugs.com/monograph/digoxin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221004328/https://www.drugs.com/monograph/digoxin.html|archive-date=21 December 2016}}</ref>

Diuretics have been a mainstay of treatment against symptoms of fluid accumulation, and include diuretics classes such as [[loop diuretic]]s (such as [[furosemide]]), [[thiazide-like diuretic]]s, and [[potassium-sparing diuretic]]s. Although widely used, evidence on their efficacy and safety is limited, except for [[mineralocorticoid antagonist]]s such as [[spironolactone]].<ref name="NICE2018ch6"/><ref name=vonLueder>{{cite journal | vauthors = von Lueder TG, Atar D, Krum H | title = Diuretic use in heart failure and outcomes | journal = Clinical Pharmacology and Therapeutics | volume = 94 | issue = 4 | pages = 490–8 | date = October 2013 | pmid = 23852396 | doi = 10.1038/clpt.2013.140 | s2cid = 7441258 }}</ref>

Anemia is an independent factor in mortality in people with chronic heart failure. Treatment of anemia significantly improves the quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates.<ref name=He2009>{{cite journal | vauthors = He SW, Wang LX | title = The impact of anemia on the prognosis of chronic heart failure: a meta-analysis and systemic review | journal = Congestive Heart Failure | volume = 15 | issue = 3 | pages = 123–30 | year = 2009 | pmid = 19522961 | doi = 10.1111/j.1751-7133.2008.00030.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nunez-Gil MI, Peraira-Moral MJ |title=Anaemia in heart failure: intravenous iron therapy |journal=e-Journal of the ESC Council for Cardiology Practice |volume=10 |issue=16 |date=19 January 2012 |url=http://www.escardio.org/communities/councils/ccp/e-journal/volume10/Pages/anemia-in-heart-failure-intravenous-iron-therapy-Peraira-Moral-J-Roberto-Nunez-Gil-Ivan-J.aspx |url-status=dead |archive-url=https://web.archive.org/web/20130603124155/http://www.escardio.org/communities/councils/ccp/e-journal/volume10/Pages/anemia-in-heart-failure-intravenous-iron-therapy-Peraira-Moral-J-Roberto-Nunez-Gil-Ivan-J.aspx |archive-date=3 June 2013 |df=dmy-all |access-date=3 October 2012 }}</ref> The [[European Society of Cardiology]] recommends screening for iron deficiency and treating with [[parenteral iron|intravenous iron]] if deficiency is found.<ref name="ESC2021"/>{{rp|pages=3668–3669}}

The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions that increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative.<ref name="Hunt-2005" />

[[Vasopressin receptor antagonist]]s can also treat heart failure. [[Conivaptan]] is the first medication approved by the US [[Food and Drug Administration]] for the treatment of euvolemic hyponatremia in those with heart failure.<ref name="US cardiology 2008"/> In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia.<ref name="US cardiology 2008"/>

[[Ivabradine]] is recommended for people with symptomatic heart failure with reduced left ventricular ejection fraction who are receiving optimized guideline-directed therapy (as above) including the maximum tolerated dose of beta-blocker, have a normal heart rhythm and continue to have a resting heart rate above 70 beats per minute.<ref name=ACC2017/> Ivabradine has been found to reduce the risk of hospitalization for heart failure exacerbations in this subgroup of people with heart failure.<ref name=ACC2017>{{cite journal | vauthors = Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, Drazner MH, Filippatos GS, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C | title = 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 | journal = Circulation | volume = 136 | issue = 6 | pages = e137–e161 | date = August 2017 | pmid = 28455343 | doi = 10.1161/CIR.0000000000000509 | doi-access = free }}</ref>