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Rational pharmacotherapy of chronic heart failure with increased endothelin-1 activity: beta-adrenoblocker nebivolol place

Abstract

Aim. To optimize chronic heart failure (CHF) pharmacotherapy, basing on endothelin (ET) system activity, functional and cardio-hemodynamic parameters, and their dynamics in beta-adrenoblocker nebivolol therapy.
Material and methods. The study included 52 patients with coronary heart disease and systolic CHF, Functional Class (FC) II-IV by NYHA. Pulmonary hypertension (PH) was registered in 27 participants. The control group included 10 age-matched healthy individuals. CHF patients were divided into two groups: Group 1 (n=28) additionally received nebivolol (5 mg/d); Group 2 (n=24) continued standard treatment. At baseline and 10 week slater, 6-minute walk test (6MWT), quality of life (QoL) questionnaire survey, and echocardiography were performed. In 40 patients, plasma ET-1 level dynamics was assessed.
Results. Ten weeks later, in nebivolol group, CHF FC decreased, 5MWT distance increased (р=0,0046) as well as
left ventricular ejection fraction, QoL significantly improved. No significant changes were observed in Group 2. Maximal ET-1 level was registered in FC IV CHF or PH patients. ET-1 concentration significantly correlated with mean and systolic pulmonary artery pressure (PAP), right ventricular myocardial diameter and wall thickness. After 10 weeks of nebivolol therapy, ET-1 level significantly decreased in CHF and PH participants (р=0,0096). ET-1 concentration dynamics in nebivolol group correlated with PAP dynamics and increased physical stress tolerance (PST).
Conclusion. ET-1 concentration increased in parallel with CHF FC and PAP increase. Nebivolol significantly improved myocardial contractility, prevented further myocardial remodeling, improved pulmonary hemodynamics, therefore enhancing PST and QoL. In PH patients nebivolol significantly decreased plasma ET-1 levels.

About the Authors

L. I. Olbinskaya
I.M. Sechenov Moscow Medical Academy, Moscow
Russian Federation


Yu. I. Naymann
I.M. Sechenov Moscow Medical Academy, Moscow
Russian Federation


References

1. Гуревич М.А., Санина Н.П.. Хохлова Т.Ф., Бувальцев В.И. Оценка клинико-гемодинамического действия небиволола у больных с хронической сердечной недостаточностью. РКЖ 2001; 2: 38-41.

2. Гомазков О.А. Система эндотелиновых пептидов: механизмы кардиоваскулярных патологий. Воп мед химии 1999; 45(4):10-7.

3. Евдокимова А.Г., Радзевич А.Э., Терещенко О.И. и др. Применение небиволола в комплексной терапии больных ИБС с хронической сердечной недостаточностью. РКЖ 2004; 48(4): 45-8.

4. Лопатин Ю.М. Европейские рекомендации по диагностике и лечению хронической сердечной недостаточности 2005 г.: новые позиции β-адреноблокаторов. CONS-MED 2005; 7(11): 926-9.

5. Российские рекомендации по лечению и диагностике ХСН. Общество специалистов по СН и секция по СН ВНОК, 2006г.

6. Brehm BR, Wolf SC, Bertsch D, et al. Effects of nebivolol on proliferation and apoptosis of human coronary artery smooth muscle and endothelial cells. Cardiovasc Res 2001; 49(2): 430-9.

7. Brixius K, Bundkirchen A, Bolck B, et al. Nebivolol, bucindolol, metoprolol and carvedilol are devoid of intrinsic sympathomimetic activity in human myocardium. Br J Pharmac 2001; 133: 1330-8.

8. Brune S, Schmidt T, Tebbe U, Kreuzer H. Hemodynamic effects of nebivolol at rest and on exertion in patients with heart failure. Angiology1990; 41(9 Pt 1): 696-701.

9. Butler J, Chomsky DB, Wilson JR. Pulmonary hypertension and exercise intolerance in patients with heart failure. JACC 1999; 34: 1802-6.

10. Cody RJ, Haas GJ, Binkley PF, et al. Plasma endothelin correlates with the extent of pulmonary hyperension in patients with chronic congestive heart failure. Circulation 1992; 85: 504-9.

11. Edes I, Gasior Z, Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure:results of the ENECA study. Eur J Heart Fail 2005; 7(4): 631-9.

12. Flather MD, Shibata MC, Coats AJS, et al. on behalf of the SENIORS Investigators Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005; 26(3): 215-25.

13. Ghio S, Magrini G, Serio A, еt аl. on behalf of the SENIORS investigators Effects of nebivolol in elderly heart failure patients with or without systolic left ventricular dysfunction: results of the SENIORS echocardiographic substudy. Eur Heart J 2006; 27(5): 562-8.

14. Ignarro LJ, Byrns RE, Trinh K, еt аl. Nebivolol: a selective beta(1)-adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide- and cyclic GMP-dependent mechanisms. Nitric Oxide 2002; 7(2): 75-82.

15. Krum H, Goldsmith R, Wilshire-Clement M, et al. Role of endothelin in the exercise intolerance of chronic heart failure. Am J Cardiol 1995; 75: 1282-3.

16. Nodari S, Metra M, Livio Dei Cas. β-Blocker treatment of patients with diastolic heart failure and arterial hypertension. A prospective, randomized, comparison of the long-term effects of atenolol vs. nebivolol. Eur J Heart Fail 2003; 5(5): 621-7.

17. Pousset F, Isnard R, Lechat P, et al. Prognostic value of plasma endothelin-1 in patients with chronic heart failure. Eur Heart J 1997; 18(2): 254-8.

18. Stoleru l, Wijns W, Van Eyll C, et al. Effects of d-nebivolol and Inebivolol on left ventricular systolic and diastolic function: comparison with d-l-nebivolol and atenolol. J Cardiovasc Pharmacol 1993; 22(2): 183-90.

19. Swedberg K, Cleland J, Dargie H, et аl. The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005; 26: 1115-40.

20. Tsutamoto T, Wada A, Maeda Y, et al. Relation between endothelin-1 spillover in the lungs and pulmonary vascular resistance in patients with chronic heart failure. JACC 1994; 23: 1427-33.

21. Wagner FD, Buz S, Knosalla C, et аl. Modulation of Circulating Endothelin-1 and Big Endothelin by Nitric Oxide Inhalation Following Left Ventricular Assist Device Implantation. Circulation 2003; 108(II): 278-84.

22. Wei CM, Lerman A, Rodeheffer RJ, et al. Endothelin in human congestive heart failure. Circulation 1994; 89: 1580-6.

23. Wisenbaugh T, Katz I, Davis J, et аl. Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy. JACC 1993; 21(5): 1094-100.


Review

For citations:


Olbinskaya L.I., Naymann Yu.I. Rational pharmacotherapy of chronic heart failure with increased endothelin-1 activity: beta-adrenoblocker nebivolol place. Cardiovascular Therapy and Prevention. 2007;6(1):61-67. (In Russ.)

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