Siroz ve kalp yetmezliği olan hastalarda tolvaptanın erken dönemde hiponatremi üzerindeki etkinliği ve güvenliği

Year 2021, Volume: 4 Issue: 2, 67 - 73, 01.07.2021

Ahmet Uyanıkoğlu , Çiğdem Cindoğlu , Süleyman Sari

Abstract

Giriş: Siroz ve kalp yetmezliği olan hastalarda hiponatremi sık görülen bir elektrolit bozukluğudur. Bu çalışmada bir vazopressör V2 reseptör antagonisti olan tolvaptan`ın sirotik hastalarda ve kalp yetmezliği olan hastalarda serum sodyum (Na) değeri üzerindeki etkisinin araştırılması amaçlanmıştır.
Materyal metod: Ocak 2018 – Haziran 2020 tarihleri arasında Harran Üniversitesi Tıp Fakültesi Hastanesi Gastroenteroloji ve Kardiyoloji kliniklerinde takip edilen, hiponatremi nedeniyle tolvaptan verilen 59 hasta değerlendirildi. Hastalara 15 mg tolvaptan verildikten sonra 0., 3. ve 5. günlerdeki Na değerleri incelendi.
Bulgular: Toplam 59 hastanın 41`i (%70) kalp yetmezliği, 18`i (%30) siroz idi. Hastaların 35`i (%59) kadın, yaş ortalaması 67.06 ± 13.35, yaş dağılımı 21 - 89 idi. Siroz hastalarında 0., 3. ve 5. günlerdeki Na değerleri sırasıyla 120.94 ± 3.88, 125.94 ± 4.20, 128.61 ± 5.58 (dağılımı sırasıyla 113–128, 120 – 134, 118 – 138) mEq/L olup, 3. ve 5. günlerde Na anlamı olarak yükselmiştir (p<0,000, p<0,0166). Kalp yetmezliği olan hastalarda 0., 3. ve 5. günlerdeki Na değerleri sırasıyla 128.68 ± 7.32, 133.43 ± 4.61, 132.77 ± 5 (dağılımı sırasıyla 111 – 143, 124 – 142, 123 – 146) mEq/L olup, 3. günde Na artışı anlamlı iken (p<.0,0166), 3 ve 5.gün arası Na artış değeri anlamlı olarak yükselmemiştir (p>0.587). Tedaviyi kesmeyi gerektirecek ciddi tan etki ve hipernatremi gelişmemiştir.
Sonuç: Tolvaptan sirozlu hastalarda, Na’yı başlangıç değerine göre 3. ve 5. günde anlamlı olarak yükseltmiştir. Kalp yetmezliğinde ise Na’yı 3.günde anlamlı yükseltirken 3.ve 5.gün arasında anlamlı yükselme sağlamamıştır. Tolvaptan sirotik ve kalb yetmezliği olan hiponatremik hastalarda erken dönemde etkili ve güvenlidir.

Keywords

siroz, kalp yetmezliği, tolvaptan, hiponatremi

Efficacy and safety of tolvaptan on hyponatremia in patients with cirrhosis and heart failure

Abstract

Introduction: Hyponatremia is a common electrolyte disorder in patiients with cirrhosis and heart failure. In this study, it was aimed to invastgate the effect of tolvaptan, a vasopressor antagonist, on serum sodium (Na) value in hyponatremic cirrhotic and heart failure patients.
Material method: 59 patients who were followed up in Harran University Medical Faculty Hospital, Gastroenterology and Cardiology clinics between January 2018 – June 2020 and given tolvaptan due to hyponatremia were evaluated. After giving 15 mg of tolvaptan to patients, Na values at 0, 3 and 5 days were examined.
Results: A total of 59 patients, 41 (70%) had heart failure, 18 (30%) had cirrhosis. 35 (59%) of the patients were female, mean age was 67.06 ± 13.35, and age distribution was 21-89 years. Na values at 0, 3, and 5 days in patients with cirrhosis are 120.94 ± 3.88, 125.94 ± 4.20, 128.61 ± 5.58 (distribution 113–128, 120 - 134, 118 - 138, respectively) and 3 and 5. days increased as meaning (p <0.000, p <0.0166). Na values at 0, 3 and 5 days in patients with heart failure are 128.68 ± 7.32, 133.43 ± 4.61, 132.77 ± 5 (distribution is 111 - 143, 124 - 142, 123 - 146, respectively) and on day 3 while Na increase was significant (p <.0.0166), Na increase value between 3 and 5 days did not increase significantly (p> 0.587). Serious adverse effects and hypernatremia that would require discontinuation of treatment have not developed.
Conclusion: In cirrhotic patients with tolvaptan, Na increased significantly according to baseline on the 3rd and 5th days. In heart failure patients, Na significantly increased on the 3rd day, but did not increase significantly between the 3rd and 5th days. Tolvaptan is effective and safe in the early period in patients with hyponatremic cirrhotic and heart failure.

Keywords

cirrhosis, heart failure, tolvaptan, hyponatremia

References

• Referans1 Peri A. Management of hyponatremia: causes, clinical aspects, differential diagnosis and treatment. Expert Rev Endocrinol Metab. 2019;14(1):13-21. doi: 10.1080/17446651.2019.1556095.
• Referans2 Shiba S, Chu PS, Nakamoto N, Yamataka K, et al. Clinical implications with tolvaptan on monitored bioimpedance-defined fluid status in patients with cirrhotic ascites: an observational study. BMC Gastroenterol. 2020;20(1):53. doi: 10.1186/s12876-020-01205-2.
• Referans3 Barajas-Galindo DE, Vidal-Casariego A, Gomez-Hoyos E, Guerra-Gonzalez M. Clinical experience with Tolvaptan outpatient use. Cost and effectiveness in 9 cases. Gac Med Mex. 2020;156(1):78-81. doi: 10.24875/GMM.19005250.
• Referans4 Sola E, Gines P. Hypervolemic Hyponatremia (Liver). Front Horm Res. 2019;52:104-112. doi: 10.1159/000493241.
• Referans5 Sakaida I, Terai S, Kurosaki M, Okada M, Hirano T, Fukuta Y. Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study). J Gastroenterol. 2020. doi: 10.1007/s00535-020-01691-x.
• Referans6 Kida Y. Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites. Dig Dis. 2019;37(3):239-246. doi: 10.1159/000494438.
• Referans7 Kin H, Matsumura K, Yamamoto Y, Fujii K, et al. Renoprotective effect of tolvaptan in patients with new-onset acute heart failure. ESC Heart Fail. 2020. doi: 10.1002/ehf2.12738.
• Referans8 Kinugawa K, Sato N, Inomata T. Effects of Tolvaptan on Volume Overload in Patients with Heart Failure. Int Heart J. 2018;59(6):1368-1377. doi: 10.1536/ihj.18-119. Epub 2018 Oct 25.
• Referans9 Kinugawa K, Sato N, Inomata T, Yasuda M, Shimakawa T, Fukuta Y. Real-World Effectiveness and Tolerability of Tolvaptan in Patients With Heart Failure　- Final Results of the Samsca Post-Marketing Surveillance in Heart Failure (SMILE) Study. Circ J. 2019;83(7):1520-1527. doi: 10.1253/circj.CJ-19-0158.
• Referans10 Kogiso T, Sagawa T, Kodama K, Taniai M, Tokushige K. Impact of continued administration of tolvaptan on cirrhotic patients with ascites. BMC Pharmacol Toxicol. 2018;19(1):87. doi: 10.1186/s40360-018-0277-3
• Referans11 Atsukawa M, Tsubota A, Takaguchi K, et al. Analysis of factors associated with the prognosis of cirrhotic patients who were treated with tolvaptan for hepatic edema. J Gastroenterol Hepatol. 2019. doi: 10.1111/jgh.14965.
• Referans12 Kanayama K, Chiba T, Kobayashi K, et al. Long-term administration of Tolvaptan to patients with decompensated cirrhosis. Int J Med Sci. 2020;17(7):874-880. doi: 10.7150/ijms.41454. eCollection 2020.
• Referans13 Wang S, Zhang X, Han T, Xie W, Li Y, Ma H, Liebe R, Weng H, Ding HG. Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia. BMC Gastroenterol. 2018;18(1):137. doi: 10.1186/s12876-018-0857-0.
• Referans14 Hiramine Y, Uto H, Mawatari S, et al. Effect of tolvaptan on the prognosis of patients with hepatic ascites. Hepatol Res. 2019;49(7):765-777. doi: 10.1111/hepr.13337.
• Referans15 Bellos I, Kontzoglou K, Psyrri A, Pergialiotis V. Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis. Dig Dis. 2019;1-9. doi: 10.1159/000503559.
• Referans16 Tajiri K, Tokimitsu Y, Ito H, et al. Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis. Dig Dis. 2018;36(4):314-321. doi: 10.1159/000489258.
• Referans17 Iwamoto T, Maeda M, Saeki I, Hidaka I, Tajima K, Ishikawa T, Takami T, Sakaida I. Analysis of tolvaptan non-responders and outcomes of tolvaptan treatment of ascites. J Gastroenterol Hepatol. 2019;34(7):1231-1235. doi: 10.1111/jgh.14524.
• Referans18 Gunderson EG, Lillyblad MP, Fine M, Vardeny O, Berei TJ. Tolvaptan for Volume Management in Heart Failure. Pharmacotherapy. 2019;39(4):473-485. doi: 10.1002/phar.2239.
• Referans19 Watanabe Y, Nara Y, Hioki H, et al. Short-term effects of low-dose tolvaptan in acute decompensated heart failure patients with severe aortic stenosis: The LOHAS registry. Int J Cardiol. 2020;305:82-86. doi: 10.1016/j.ijcard.2020.02.017.
• Referans20 Uojima H, Hidaka H, Tanaka Y, et al. Furosemide Dose Changes Associated with Furosemide/Tolvaptan Combination Therapy in Patients with Cirrhosis. Dig Dis. 2020;38(1):38-45. doi: 10.1159/000501267.
• Referans21 Ma G, Ma X, Wang G, Teng W, Hui X. Effects of tolvaptan add-on therapy in patients with acute heart failure: meta-analysis on randomised controlled trials. BMJ Open. 2019;9(4):e025537. doi: 10.1136/bmjopen-2018-025537.
• Referans22 Matsumura K, Morishita S, Taniguchi N, et al. Prognostic factors for long-term outcomes in acute decompensated heart failure patients under tolvaptan treatment. Heart Vessels. 2019;34(4):607-615. doi: 10.1007/s00380-018-1290-6.
• Referans23 Gao WQ1, Meng XD, Sun Z. Efficacy of tolvaptan for chronic heart failure: Study protocol for a systematic review of randomized controlled trial. Medicine (Baltimore). 2019;98(7):e14540. doi: 10.1097/MD.0000000000014540.