Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study☆
Introduction
In cancer therapy, several cytotoxic drugs may cause cardiotoxicity which is associated with poor short- and long-term outcome. Anthracycline has long been demonstrated to improve survival in breast cancer patients. However, the development of dose-related, cumulative, and essentially irreversible cardiac toxicity undermines its long-term clinical benefits [1].
The proposed mechanisms of antracycline-induced cardiotoxicity (AIC) include the formation of free reactive oxygen radicals, direct DNA damage and/or interference with DNA repair, apoptosis, activation of immune reactions involving antigen-presenting cells in the heart, changes in calcium transport, histamine release and activation of coagulation system leading to coronary artery thrombosis [1], [2], [3], [4], [5], [6].
Free radical hypothesis has been suggested to be one of the major determinants for AIC [7], [8]. Animal experiments demonstrated that numerous agents could potentially counteract chemotherapy toxicity. Promising results have been reported in these animal studies involving angiotensin-converting enzyme inhibitors [9], telmisartan [10], carvedilol [11], nebivolol [12], erythropoietin [13], bosentan [14], carbon monoxide (CO) and bilirubin [15] on AIC. However, data are scant about their clinical use in humans.
Of them, nebivolol is a β1-selective (i.e. cardio-selective) adrenergic receptor antagonist (at doses up to 10 mg/d), with vasodilatory effects mediated by nitric oxide (NO) release, a mechanism possibly triggered by activation of β3-receptors [16], [17]. In this randomized, double-blind, placebo-controlled clinical study, we aimed to evaluate the effect of prophylactic nebivolol use on prevention of AIC in breast cancer patients receiving anthracycline-based chemotherapy.
Section snippets
Study population
From October 2007 to September 2008, 45 consecutive patients admitted to the medical oncology department of the Erciyes University Medical School for breast cancer and planned antracycline-based chemotheraphy were enrolled. All patients were female. Exclusion criteria included the presence of cardiomyopathy (dilated, restrictive or hypertrophic) detected by baseline echocardiography, coronary heart disease, moderate or severe aortic and/or mitral valve disease, prior chemotherapy or
Results
Patients received low dose nebivolol treatment did not experience any symptomatic hypotention or bradycardia. There were no heart failure hospitalization or death occurred during the study period. No patient from each group discontinued the nebivolol or placebo therapy because of their side effects.
Of the 45 consecutive patients enrolled in the study, 27 were randomized to oral nebivolol, and 18 were randomized to placebo. Baseline clinical and echocardiographic characteristics are listed in
Discussion
This small, randomized, placebo-controlled study demonstrated prophylactic nebivolol use may prevent LV enlargement and functional impairment caused by anthracycline therapy.
Anthracycline-induced cardiotoxicity (AIC) causes severe morbidity and even mortality in cancer patients. The fear of developing cardiotoxicity may also limit the dose of the drug to be used and leads to reduced tumour response. Cardiotoxicity is mainly caused by anthracyclines although a number of other chemotherapeutic
Acknowledgments
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References (35)
- et al.
Cardiotoxicity of cytotoxic drugs
Cancer Treat Rev
(2004) - et al.
L-carnitine reduces doxorubicin-induced apoptosis through a prostacyclin-mediated pathway in neonatal rat cardiomyocytes
Int J Cardiol
(2011) - et al.
Beneficial effects of angiotensin-converting enzyme inhibition in adriamycin-induced cardiomyopathy in hamsters
Jpn J Pharmacol
(2002) - et al.
Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats
Life Sci
(1999) - et al.
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) - et al.
5-Fluorouracil cardiotoxicity: a unique mechanism for ischaemic cardiopathy and cardiac failure?
Eur J Cancer
(1996) - et al.
Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer
Breast
(2004) Vokes EE 5-Fluorouracil cardiotoxicity: a critical review
Ann Oncol
(1990)- et al.
Protective effects of carvedilol against anthracycline-induced cardiomyopathy
J Am Coll Cardiol
(2006) - et al.
Study of the effect of nebivolol intervention on outcomes and rehospitalisation in seniors with heart failure (SENIORS). Rationale and design
Inter J Cardiol
(2002)
Nebivolol: The somewhat-different beta-adrenergic receptor blocker
J Am Coll Cardiol
Dendritic cells in the hearts of spontaneously hypertensive rats treated with doxorubicin with or without ICRF-187
Am J Pathol
Cardiomyocyte apoptosis and progression of heart failure to transplantation
Eur J Clin Invest
Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin
Cancer Res
Cardiotoxicity of the antiproliferative compound fluorouracil
Drugs
Chemoprotectants for cancer chemotherapy
Semin Oncol
A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine
Semin Oncol
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Conflict of Interest: None.