Current Role of Digoxin in Heart Failure as Per Guidelines and DIGIT-HF trial of Digitoxin

Current Role of Digoxin in Heart Failure as Per Guidelines and DIGIT-HF trial of Digitoxin

Use of digoxin in heart failure has come down markedly over the past decades due to concerns of toxicity and availability of more effective medications. Concern for toxicity is because of the narrow therapeutic window of digoxin along with interactions with other cardiovascular drugs and in those with renal dysfunction, which can enhance toxicity. Though an initial loading dose was given earlier, it is no longer used. As per the 2021 ESC guidelines, digoxin may be considered in heart failure with reduced ejection fraction, in sinus rhythm for reducing risk of hospitalizations, though there is no mortality benefit. It may also be useful in those with associated atrial fibrillation and fast ventricular rate when other therapeutic options are not feasible. Caution is needed in females, elderly, frail, malnourished and hypokalemic persons. Serum concentrations below 1.2 ng/mL should be aimed at [1].

In those with reduced renal function another related medication digitoxin could be considered. DIGIT-HF trial evaluated the role of digitoxin in advanced chronic heart failure [2]. An analysis of 307 patients randomized to digitoxin showed that in patients with HFrEF, treatment with digitoxin may be started at 0.05 mg daily in those with either female gender, estimated glomerular filtration rate below 50 ml/min/1.73 sq. m body surface area, body mass index less than 27 kg/sq. m, or age 75 years or more. In others, dose suggested was 0.07 mg daily, for digitoxin [3].

References

  1. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Erratum in: Eur Heart J. 2021 Oct 14;: PMID: 34447992.
  2. Bavendiek U, Berliner D, Dávila LA, Schwab J, Maier L, Philipp SA, Rieth A, Westenfeld R, Piorkowski C, Weber K, Hänselmann A, Oldhafer M, Schallhorn S, von der Leyen H, Schröder C, Veltmann C, Störk S, Böhm M, Koch A, Bauersachs J; DIGIT-HF Investigators and Committees (see Appendix). Rationale and design of the DIGIT-HF trial (DIGitoxin to Improve ouTcomes in patients with advanced chronic Heart Failure): a randomized, double-blind, placebo-controlled study. Eur J Heart Fail. 2019 May;21(5):676-684. doi: 10.1002/ejhf.1452. Epub 2019 Mar 20. PMID: 30892806; PMCID: PMC6607489.
  3. Bavendiek U, Großhennig A, Schwab J, Berliner D, Liu X, Maier L, Gaspar T, Rieth A, Philipp S, Hambrecht R, Westenfeld R, Münzel T, Winkler S, Hülsmann M, Westermann D, Zdravkovic M, Lichtinghagen R, von der Leyen H, Zimmermann S, Veltmann C, Böhm M, Störk S, Koch A, Bauersachs J. Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial. Clin Res Cardiol. 2023 Aug;112(8):1096-1107. doi: 10.1007/s00392-023-02199-z. Epub 2023 Apr 22. PMID: 37087503; PMCID: PMC10359203.