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Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Analysis of Intoxication, Rehospitalization, and One-year Survival of Heart Failure Patients Receiving Digoxin at Harapan Kita National Cardiovascular Center, Jakarta, Indonesia: A Cross Section-observational Study

Author(s): Nafrialdi Nafrialdi*, Cindy Tiaranita, Fransiscus D. Suyatna and Bambang Budi Siswanto

Volume 18, Issue 2, 2023

Published on: 20 August, 2022

Page: [246 - 252] Pages: 7

DOI: 10.2174/1574886317666220520114417

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Abstract

Background: Despite being the oldest therapy for heart failure, the use of digoxin is still controversial due to the narrow margin of safety. In Indonesia, digoxin is still considered one of the treatments for heart failure. However, analysis of intoxication has never been reported. This study aims to analyze the occurrence of digoxin intoxication, rate of rehospitalization and one-year survival in heart failure patients under digoxin treatment.

Methods: A cross section-observational study was conducted at Harapan Kita National Cardiovascular Centre from January 2017 to December 2018 on heart failure patients who received digoxin therapy and had data on serum digoxin level. Intoxication was defined as the presence of specific ECG alteration(s), at least one extra-cardiac symptom(s) and further classified as definite (serum digoxin >2 ng/mL), probable (serum digoxin 0.91-1.99 ng/mL), or possible (serum digoxin 0.5-0.9 ng/mL). Risk factors of intoxication were analyzed by Chi-square test, and one-year survival was analyzed with Kaplan Meyer method.

Results: 54 of 195 patients (27.69%) were classified as having intoxication, consisting of 32 (16.41%) definite, 19 (9.74%) probable, and 3 (1.54%) possible. Renal insufficiency was revealed as a significant influencing factor of digoxin intoxication with RR 2.48 (CI 1.13-5.464, p=0.016). Overall one-year survival of patients receiving digoxin was 259 days in the intoxication group and 307 days in the non-intoxication group. One-year rehospitalization was 11.8% in patients who received digoxin and 29.2% in those without digoxin (p=0.085).

Conclusion: The proportion of digoxin intoxication in heart failure patients was 27.69%. Renal insufficiency was revealed as a significant influencing factor of intoxication. There was a tendency of reduced hospitalization in those who received digoxin.

Keywords: Digoxin intoxication, heart failure, risk factors, survival, rehospitalization, treatment.

[1]
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016; 18(8): 891-975.
[http://dx.doi.org/10.1002/ejhf.592] [PMID: 27207191]
[2]
Reyes EB, Ha JW, Firdaus I, et al. Heart failure across Asia: Same healthcare burden but differences in organization of care. Int J Cardiol 2016; 223: 163-7.
[http://dx.doi.org/10.1016/j.ijcard.2016.07.256] [PMID: 27541646]
[3]
van Riet EES, Hoes AW, Wagenaar KP, Limburg A, Landman MAJ, Rutten FH. Epidemiology of heart failure: The prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Syst Rev 2016; 18(3): 242-52.
[http://dx.doi.org/10.1002/ejhf.483] [PMID: 26727047]
[4]
Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev 2017; 3(1): 7-11.
[http://dx.doi.org/10.15420/cfr.2016:25:2] [PMID: 28785469]
[5]
Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: A report from the American Heart Association. Circulation 2019; 139(10): e56-e528.
[http://dx.doi.org/10.1161/CIR.0000000000000659] [PMID: 30700139]
[6]
Ziff OJ, Lane DA, Samra M, et al. Safety and efficacy of digoxin: Systematic review and meta-analysis of observational and controlled trial data. BMJ 2015; 351: h4451.
[http://dx.doi.org/10.1136/bmj.h4451] [PMID: 26321114]
[7]
Eschenhagen T. Therapy of heart failure Goodman & Gilman’s The pharmacological basis of therapeutics. (13th ed.). New York: McGraw-Hill, Medical Publishing Division 2018; pp. 527-46.
[8]
Kirilmaz B, Saygi S, Gungor H, et al. Digoxin intoxication: An old enemy in modern era. J Geriatr Cardiol 2012; 9(3): 237-42.
[http://dx.doi.org/10.3724/SP.J.1263.2012.01101] [PMID: 23097652]
[9]
Goldberger ZD, Goldberger AL. Therapeutic ranges of serum digoxin concentrations in patients with heart failure. Am J Cardiol 2012; 109(12): 1818-21.
[http://dx.doi.org/10.1016/j.amjcard.2012.02.028] [PMID: 22502901]
[10]
Katzung BG. Drug use in heart failure Katzung BG, Trevor AJ. (14th ed.). Basic & Clinical Pharmacology 2018; pp. 212-27.
[11]
Bauman JL, Didomenico RJ, Galanter WL. Mechanisms, manifestations, and management of digoxin toxicity in the modern era. Am J Cardiovasc Drugs 2006; 6(2): 77-86.
[http://dx.doi.org/10.2165/00129784-200606020-00002] [PMID: 16555861]
[12]
Kanji S, MacLean RD. Cardiac glycoside toxicity: More than 200 years and counting. Crit Care Clin 2012; 28(4): 527-35.
[http://dx.doi.org/10.1016/j.ccc.2012.07.005] [PMID: 22998989]
[13]
Butler J, Braunwald E, Gheorghiade M. Recognizing worsening chronic heart failure as an entity and an end point in clinical trials. JAMA 2014; 312(8): 789-90.
[http://dx.doi.org/10.1001/jama.2014.6643] [PMID: 25157719]
[14]
Cummings ED, Swoboda HD. Digoxin Toxicity https://www.ncbi.nlm.nih.gov/books/NBK470568/
[15]
The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336(8): 525-33.
[http://dx.doi.org/10.1056/NEJM199702203360801] [PMID: 9036306]
[16]
Muchtar A, Suyatna FD. Obat antiaritmia. Nafrialdi, Instiaty: Farmakologi dan Terapi 2016; pp. 318-44.
[17]
Beller GA, Smith TW, Abelmann WH, Haber E, Hood WB Jr. Digitalis intoxication. A prospective clinical study with serum level correlations. N Engl J Med 1971; 284(18): 989-97.
[http://dx.doi.org/10.1056/NEJM197105062841801] [PMID: 5553483]
[18]
Nafrialdi N, Martina SJ, Djer MM, et al. Plasma digoxin levels and ejection fraction in pediatric heart failure. Paediatr Indones 2015; 55(6): 322-7.
[http://dx.doi.org/10.14238/pi55.6.2015.06]
[19]
Albert CL, Kamdar F, Hanna M. Contemporary controversies in digoxin use in systolic heart failure. Curr Heart Fail Rep 2016; 13(5): 197-206.
[http://dx.doi.org/10.1007/s11897-016-0302-z] [PMID: 27696142]
[20]
See I, Shehab N, Kegler SR, Laskar SR, Budnitz DS. Emergency department visits and hospitalizations for digoxin toxicity: United States, 2005 to 2010. Circ Heart Fail 2014; 7(1): 28-34.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.113.000784] [PMID: 24300242]
[21]
Ahmed A, Bourge RC, Fonarow GC, Patel K, Morgan CJ, et al. Digoxin use and lower 30-day All-cause readmission for Medicare beneficiaries hospitalized for heart failure. 2014; 127(1): 61-70.
[22]
Uretsky BF, Young JB, Shahidi FE, Yellen LG, Harrison MC, Jolly MK. Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: Results of the PROVED trial. J Am Coll Cardiol 1993; 22(4): 955-62.
[http://dx.doi.org/10.1016/0735-1097(93)90403-N] [PMID: 8409069]
[23]
Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993; 329(1): 1-7.
[http://dx.doi.org/10.1056/NEJM199307013290101] [PMID: 8505940]

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