DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20195537

Role of nebivolol in anthracycline-induced cardiotoxicity

John Satish Rudrapogu, Biju Govind, Adinarayana Unnagiri

Abstract


Background: Anthracyclines are extensively used in the treatment of breast cancer. However, these therapeutic agents are responsible for chemotherapy-induced cardiotoxicity. Aim of this study was to assess the effect of use of prophylactic nebivolol for the prevention of anthracycline-induced cardiotoxicity in breast cancer patients.

Methods: This was a prospective, randomized, single-blind, and placebo-controlled trial involving 80 participants with breast cancer, scheduled to undergo chemotherapy with doxorubicin. Patients were randomly divided into two groups: the nebivolol group (n=40) to receive nebivolol 5 mg daily and the placebo group (n=40) to receive placebo. All patients were evaluated with baseline Electrocardiogram (ECG) and echocardiography prior to treatment, and at the 6-month follow-up. Echocardiography included 2D echocardiography, colour doppler and tissue doppler imaging.

Results: The study groups had comparable baseline echocardiographic variables. At the 6-month echocardiographic follow-up, there were no changes of statistical significance in any 2D echocardiographic variables in either group. However, there were minimal reductions of 0.4% in left ventricular ejection fraction in the nebivolol group (62.2±4.4% to 61.9±4.2%, p=0.75) and 1.6% in the placebo group (62.8±3.6% to 61.8±3.2%, p=0.18). Doppler examinations also did not reveal any statistically significant changes in variables such as peak A velocity, peak E velocity, E/A ratio, isovolumic relaxation time, and isovolemic contraction time in either group.

Conclusions: Prophylactic use of nebivolol treatment may possess cardioprotective properties against anthracycline-induced cardiotoxicity in breast cancer patients although not statistically significant in this study.


Keywords


Anthracycline, Beta-blockers, Cardiotoxicity, Echocardiography, Left ventricular ejection fraction, Nebivolol

Full Text:

PDF

References


Porter PL. Global trends in breast cancer incidence and mortality. Salud publica de Mexico. 2009;51:s141-6.

Babu GR, Lakshmi SB, Thiyagarajan JA. Epidemiological correlates of breast cancer in South India. Asian Paci J Cancer Preve. 2013;14(9):5077-83.

Ali I, Wani WA, Saleem K. Cancer Scenario in India with Future Perspectives. Cancer Ther. 2011 Jan 1;8.

Barbosa RR, Bourguignon TB, Torres LD, Arruda LS, Jacques TD, Serpa RG, et al. Anthracycline-associated cardiotoxicity in adults: systematic review on the cardioprotective role of beta-blockers. Revista Associação Médica Brasil. 2018 Aug;64(8):745-54.

Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013 Sep 1;167(5):2306-10.

Oreto L, Todaro MC, Umland MM, Kramer C, Qamar R, Carerj S, et al. Use of echocardiography to evaluate the cardiac effects of therapies used in cancer treatment: what do we know?. J Am Soc Echocard. 2012 Nov 1;25(11):1141-52.

Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardio Pharmacol. 1999 Dec 1;34(6):879-86.

Mason RP, Kalinowski L, Jacob RF, Jacoby AM, Malinski T. Nebivolol reduces nitroxidative stress and restores nitric oxide bioavailability in endothelium of black Americans. Circulation. 2005 Dec 13;112(24):3795-801.

Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Imaging. 2015 Feb 18;16(3):233-71.

de Nigris F, Rienzo M, Schiano C, Fiorito C, Casamassimi A, Napoli C. Prominent cardioprotective effects of third generation beta blocker nebivolol against anthracycline-induced cardiotoxicity using the model of isolated perfused rat heart. Eur J Cancer. 2008 Feb 1;44(3):334-400.

Mohamed EA, Kassem HH. Protective effect of nebivolol on doxorubicin-induced cardiotoxicity in rats. Archi Med Sci: AMS. 2018 Oct;14(6):1450.

Cochera F, Dinca D, Bordejevic DA, Citu IM, Mavrea AM, Andor M, et al. Nebivolol effect on doxorubicin-induced cardiotoxicity in breast cancer. Cancer Manag Res. 2018;10:2071.

Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer: Inter Int J Am Cancer Soc. 2003 Jun 1;97(11):2869-79.

Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014 Sep 2;64(9):938-45.