Editing Digoxin (section)

== Medical uses ==

=== Irregular heartbeat ===
The most common indications for digoxin are [[atrial fibrillation]] and [[atrial flutter]] with rapid [[ventricle (heart)|ventricular]] response,<ref>{{cite journal | vauthors = Sticherling C, Oral H, Horrocks J, Chough SP, Baker RL, Kim MH, Wasmer K, Pelosi F, Knight BP, Michaud GF, Strickberger SA, Morady F | display-authors = 6 | title = Effects of digoxin on acute, atrial fibrillation-induced changes in atrial refractoriness | journal = Circulation | volume = 102 | issue = 20 | pages = 2503–8 | date = November 2000 | pmid = 11076824 | doi = 10.1161/01.CIR.102.20.2503 | s2cid = 127927 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hallberg P, Lindbäck J, Lindahl B, Stenestrand U, Melhus H | title = Digoxin and mortality in atrial fibrillation: a prospective cohort study | journal = European Journal of Clinical Pharmacology | volume = 63 | issue = 10 | pages = 959–71 | date = October 2007 | pmid = 17684738 | doi = 10.1007/s00228-007-0346-9 | s2cid = 30951337 }}</ref> especially in older or less active patients,<ref>{{cite book |title=Kumar and clark's clinical medicine |date=2017 |publisher=Elsevier |location=Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto |isbn=9780702066009 |page=972 |edition=9th}}</ref> though [[beta blocker]]s and/or [[calcium channel blocker]]s may be preferred in some patients, such as younger more active ones, or those without heart failure or hemodynamic instability.<ref name=Craig2019>{{cite journal | vauthors = January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW | display-authors = 6 | title = 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons | journal = Circulation | volume = 140 | issue = 2 | pages = e125–e151 | date = July 2019 | pmid = 30686041 | doi = 10.1161/CIR.0000000000000665 | s2cid = 59304609 | doi-access = free }}</ref>

Early observational studies showed an increased risk of death in patients taking digoxin, despite an attempt to allow for other risk factors for death (so-called [[propensity score matching]]).<ref>{{cite journal | vauthors = Ouyang AJ, LvYN, Zhong HL, Wen JH, Wei XH, Peng HW, Zhou J, Liu LL | display-authors = 6 | title = Meta-analysis of digoxin use and risk of mortality in patients with atrial fibrillation | language = English | journal = The American Journal of Cardiology | volume = 115 | issue = 7 | pages = 901–906 | date = April 2015 | pmid = 25660972 | doi = 10.1016/j.amjcard.2015.01.013 | doi-access = free }}</ref><ref name=Vamos2015>{{cite journal | vauthors = Vamos M, Erath JW, Hohnloser SH | title = Digoxin-associated mortality: a systematic review and meta-analysis of the literature | journal = European Heart Journal | volume = 36 | issue = 28 | pages = 1831–1838 | date = July 2015 | pmid = 25939649 | doi = 10.1093/eurheartj/ehv143 | doi-access = free }}</ref> However, systematic reviews focusing on [[randomised controlled trial|randomised controlled trials]] of digoxin (which ensured similarity between patients on digoxin, and those not on it) showed no difference in mortality.<ref>{{cite journal | vauthors = Sethi NJ, Nielsen EE, Safi S, Feinberg J, Gluud C, Jakobsen JC | title = Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials | journal = PLOS ONE | volume = 13 | issue = 3 | pages = e0193924 | date = 2018-03-08 | pmid = 29518134 | pmc = 5843263 | doi = 10.1371/journal.pone.0193924 | bibcode = 2018PLoSO..1393924S | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D | display-authors = 6 | title = Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data | journal = BMJ | volume = 351 | pages = h4451 | date = August 2015 | pmid = 26321114 | pmc = 4553205 | doi = 10.1136/bmj.h4451 }}</ref> Evidence suggested the increased mortality in patients taking digoxin was due to their having worse heart disease than those not taking it.<ref name="Ziff_2015">{{cite journal | vauthors = Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D | display-authors = 6 | title = Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data | journal = BMJ | volume = 351 | issue =  | pages = h4451 | date = August 2015 | pmid = 26321114 | pmc = 4553205 | doi = 10.1136/bmj.h4451 }}</ref> Cardiac arrhythmias may also occur when patients are prescribed digoxin alongside [[Thiazide|thiazides]] and [[Loop diuretic|loop diuretics]].<ref name="Kumar & Clark">{{cite book |title=Kumar and Clark's clinical medicine |date=2017 |publisher=Elsevier |location=Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto |isbn=9780702066009 |page=24 |edition=9th}}</ref>

=== Heart failure ===
[[Digitalis]] (i.e. extracts, including digoxin, from the plant genus ''Digitalis'') was the first drug used to treat [[dropsy]] (swollen ankles—a symptom of heart failure) following its discovery by [[William Withering]].<ref>{{cite book | vauthors = Withering W | url = https://archive.org/details/b21517356 | title = An Account of the Foxglove and some of its Medical Uses | location = Birmingham, England | publisher = M. Swinney | date =  1785 }}</ref> Alongside [[diuretics]], it was the mainstay of treatment for heart failure for over a century. Since the introduction of other drugs with better outcomes and fewer adverse effects, it is generally now only used where heart failure is associated with atrial fibrillation and or a rapid ventricular rate.<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 | display-authors = 6 | 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 | publisher = European Society of Cardiology | doi-access = free }}</ref> In certain circumstances it may be used under specialist guidance in addition to, or instead of, the recommended first-line treatments of  [[ACE inhibitor]], [[beta blocker]], [[Antimineralocorticoid|mineralocorticoid antagonist]], and [[SGLT-2 inhibitor]], where they are not effective or not tolerated. <ref>{{cite journal | vauthors = Ezekowitz JA, O'Meara E, McDonald MA, Abrams H, Chan M, Ducharme A, Giannetti N, Grzeslo A, Hamilton PG, Heckman GA, Howlett JG, Koshman SL, Lepage S, McKelvie RS, Moe GW, Rajda M, Swiggum E, Virani SA, Zieroth S, Al-Hesayen A, Cohen-Solal A, D'Astous M, De S, Estrella-Holder E, Fremes S, Green L, Haddad H, Harkness K, Hernandez AF, Kouz S, LeBlanc MH, Masoudi FA, Ross HJ, Roussin A, Sussex B | display-authors = 6 | title = 2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure | journal = The Canadian Journal of Cardiology | volume = 33 | issue = 11 | pages = 1342–1433 | date = November 2017 | pmid = 29111106 | doi = 10.1016/j.cjca.2017.08.022 | doi-access = free }}</ref><ref name="ESC2021"/>

=== Abortion ===
Digoxin is also used intrafetally or amniotically during [[abortions]] in the late second trimester and third trimester of pregnancy. It typically causes [[fetal demise]] (measured by cessation of cardiac activity) within hours of administration.<ref>{{cite book |url= https://books.google.com/books?id=iK7xrRr2p9sC |title=Management of Unintended and Abnormal Pregnancy: Comprehensive Abortion Care | vauthors = Paul M, Lichtenberg S, Borgatta L, Grimes DA, Stubblefield PG, Creinin MD |date=2011-08-24|publisher=John Wiley & Sons|isbn=9781444358476 |url-status=live|archive-url= https://web.archive.org/web/20170908135429/https://books.google.com/books?id=iK7xrRr2p9sC |archive-date=2017-09-08 }}</ref>