Yüksek serum digoksin konsantrasyonu risk faktörlerinin değerlendirilmesi direkt oral antikoagülan ajanlar ve digoksin arasındaki etkileşim

Amaç:Digoksin, pozitif inotropik özelliğe sahip anti-aritmik bir ilaçtır. Esas olarak valvüler olmayan atriyal fibrilasyonda kalp hızını kontrol etmek ve kalp yetmezliğinde ejeksiyon fraksiyonunu iyileştirmek için kullanılır. Son yıllarda digoksin ve yeni ilaç kombinasyonlarının kullanım sıklığı artmaktadır. Bu nedenle, doğrudan oral antikoagülan ajanlar ile kardiyovasküler ilaçlar arasındaki farmakokinetik etkileşimi değerlendirmek, zehirlenmeler için gereklidir.Gereç ve Yöntemler:Hastalar Serum Digoksin Konsantrasyonları seviyeleri ve digoksin intoksikasyonları retrospektif risk faktörlerine göre değerlendirildi. Serum Digoxin Konsantrasyonu seviyeleri <1 ng / ml düşük, 1-2 ng / ml tedavi aralığı, 2.1-2.4 ng / ml yüksek ve> 2.4 ng / ml toksisite olarak kabul edilmektedir.Bulgular:Çalışma 248 kadın (% 60,2) ve 160 erkek hastadan (% 39,2) oluşturuldu. Hastaların ortalama yaşı 70,5 idi. 408 hastanın serum digoksin konsantrasyonları; % 44.81’i düşük terapötik aralıkta, % 34.41’i terapötik aralıkta, % 6.23’ü yüksek terapötik aralıkta, % 14.55’i toksik terapötik aralıkta saptanmıştır. Ortalama glomerüler filtrasyon hızı 58.45 ve ortalama Serum Digoxin Konsantrasyonu 1.36 ng / ml idi. Yaş ile Serum Digoxin Konsantrasyonu arasındaki istatistiksel olarak anlamlı ilişki % 16,3 idi (p <0,05). Glomerüler Filtrasyon hızı ve Serum Digoxin konsantrasyonu arasında istatistiksel olarak anlamlı bir ilişki vardı; biri artarken diğeri azaldı (p <0,05). Aterosklerotik kalp hastalığı olmayan hastalarda Serum Digoxin konsantrasyonu, aterosklerotik kalp hastalığı olanlardan anlamlı olarak düşüktü (p <0.05). Serum Digoksin konsantrasyonları, rivaroksaban ile tedavi edilen hastalarda anlamlı olarak daha yüksekti ve bunların oranları 0.05 düzeyinde birbirinden önemli ölçüde farklıydı. Sonuç: Günümüzde digoksin ve direkt oral antikoagülanların birlikte kullanım sıklığı artmaktadır. Digoksinin terapötik düzeyinin dar olması, ilaç-ilaç etkileşimleri nedeniyle yakın takibi gerektirir.

Anahtar Kelimeler:

serum digoksin konsantrasyonu, ilaç etkileşimi, direkt oral antikoagülan

Evaluating high serum digoxin concentration risk factors interaction between direct oral anticoagulant agents and digoxin

Aim:Digoxin is an anti-arrhythmic drug that also has a positive inotropic property. It is mainly used to control heart rate in nonvalvular atrial fibrillation, and improve ejection fraction in heart failure. In recent years, the frequency of digoxin and a combination of new drug using has been increasing. Therefore, to assess the pharmacokinetic interaction between direct oral anticoagulant agents and cardiovascular drugs is necessary for intoxications. Material and Methods:Patients Serum Digoxin Concentrations levels and digoxin intoxications were evaluated according to risk factors investigated retrospectively Patients Serum Digoxin Concentrations levels <1 ng/ml is accepted as low, 1-2 ng/ml therapeutic range, 2.1-2.4 ng/ml is high and >2.4 ng/ml toxicity. Results:The study consisted of 248 females (60.2%) and 160 males (39.2%). The mean age of the patients was 70.5 years. The average age of patients was 70.5 years. Serum digoxin concentrations of 408 patients; 44.81% were detected in the low therapeutic range, 34.41% in the therapeutic range, 6.23% in the high therapeutic range, 14.55% in the toxic therapeutic range. The mean glomerular filtration rate was 58.45, and the mean Serum Digoxin Concentration was 1.36 ng/ml. The statistically significant relationship between age and Patients Serum Digoxin Concentration was 16.3% (p <0.05). There was a statistically significant relationship between Glomerular Filtration Rate and Serum Digoxin Concentrations; one increased and the other decreased (p <0.05). In patients without atherosclerotic heart disease, Serum Digoxin Concentration was significantly lower than those with atherosclerotic heart disease(p< 0.05). Serum Digoxin Concentrations were significantly higher in patients treated with rivaroxaban, the proportions of which differ significantly from each other at the 0.05 level. Conclusion:Nowadays, the frequency of using digoxin and direct oral anticoagulants together is increasing. The narrow therapeutic level of digoxin necessitates close monitoring due to drug-drug interactions.

Keywords:

serum digoxin concentration, drug interaction, direct oral anticoagulant,

PDF

___

1. Hollman A. Drug for atrial fibrillation. Digoxin comes from Digitalis lanata. BMJ. 1996; 312: 912
2. Lee G, Hendriks J. Digoxin - Don’t dismiss it just yet. Eur J Cardiovasc Nurs. 2017; 16: 464–5.
3. Roger VL, Go AS, Lloyd-Jones DM et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15. Erratum in: Circulation. 2011 Feb 15;123(6):e240. Erratum in: Circulation 2011; 124: 426.
4. Freeman J V., Yang J, Sung SH, Hlatky MA, Go AS. Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure. Circ Cardiovasc Qual Outcomes 2013; 6: 525–33.
5. Adams KF, Ghali JK, Herbert Patterson J et al. A perspective on re-evaluating digoxin’s role in the current management of patients with chronic systolic heart failure: Targeting serum concentration to reduce hospitalization and improve safety profile. Eur J Heart Fail 2014; 16: 483–93.
6. Cheng JWM, Rybak I. Use of digoxin for heart failure and atrial fibrillation in elderly patients. Am J Geriatr Pharmacother 2010; 8: 419–27.
7. England TN. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525–33.
8. Kotecha D, Bunting K V, Gill SK et al. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life the RATE-AF Randomized Clinical Trial 2021; 324: 2497–508.
9. Aronis KN, Hylek EM. Evidence gaps in the era of non-vitamin K oral anticoagulants. J Am Heart Assoc 2018; 7: 7338
10. Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomised trials. Lancet 2014; 383: 955–62.
11. Van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman M V. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: A systematic review and meta-analysis. J Thromb Haemost 2014; 12: 320–8.
12. Kapoor A, Ellis A, Shaffer N et al. Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis. J Thromb Haemost 2017; 15: 284–94.
13. Sakaeda T, Nakamura T, Okumura K. MDR1 genotype-related pharmacokinetics and pharmacodynamics. Biol Pharm Bull 2002; 25: 1391–400.
14. Al-Shawi MK, Omote H. The remarkable transport mechanism of P-glycoprotein: A multidrug transporter. J Bioenerg Biomembr 2005; 37: 489–96.
15. Eberl S, Renner B, Neubert A et al. Role of P-glycoprotein inhibition for drug interactions: Evidence from in vitro and pharmacoepidemiological studies. Clin Pharmacokinet 2007; 46: 1039–49.
16. Fromm M, Kim R. Handbook of Experimental Pharmacology 201; Drug Transporters. 2011.
17. Adams KF, Gheorghiade M, Uretsky BF, Patterson JH, Schwartz TA, Young JB. Clinical benefits of low serum digoxin concentrations in heart failure. J Am Coll Cardiol 2002; 39: 946–53.
18. Adams KF, Patterson JH, Gattis WA et al. Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: A retrospective analysis. J Am Coll Cardiol 2005; 46: 497–504.
19. Ahmed A, Rich MW, Love TE et al. Digoxin and reduction in mortality and hospitalization in heart failure: A comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006; 27: 178–86.
20. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: Executive summary: A report of the American college of cardiology foundation/american heart association task force on practice guidelines. J Am Coll Cardiol 2013; 62: 1495–539.
21. Heart Failure Society of America, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC, Stevenson WG, Tang WH, Teerlink JR, Walsh MN. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2019; 16: 1-194.
22. Mcmurray JJV, Adamopoulos S, Anker SD et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012. Eur J Heart Fail 2012; 14: 803–69.
23. Adams KF, Butler J, Patterson JH et al. Dose response characterization of the association of serum digoxin concentration with mortality outcomes in the Digitalis Investigation Group trial. Eur J Heart Fail 2016; 18: 1072–81.
24. Sokol J, Nehaj F, Ivankova J, Mokan M. Interaction between direct factor Xa inhibitors and digoxin. Am J Ther 2019; 26: 649–52.
25. Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol 2013; 61: 2495–502.