Rational Pharmacotherapy in Cardiology

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Aim. To study influence of ivabradine as compared with bisoprolol on clinical and hemodynamic indices, exercise tolerance, endothelial function, quality of life (QL) and erectile function in patients with ischemic heart disease. Material and methods. 60 males with stable angina pectoris were enrolled into comparative randomized crossover open study. One half of patients randomly received ivabradine during 14 days with replace it with bisoprolol for the next 3 months, another half of patients received compared drugs in the reverse order . Treadmill-test and flow-mediated dilatation (FMD) test were performed initially and after 14 days of treatment with each drug. QL and erectile function were evaluated after 3 months with Seattle Angina Questionnaire (SAQ) and International Index of Erectile Function (IIEF-5), respectively. Results. Heart rate reduced by 16.7±4.6 (p<0.005) and 16.4±4.8 bpm (p<0.005) after 2 weeks of treatment with bisoprolol and ivabradine, respectively. 30 (50.0%) and 31 (51.7%) patients treated with bisoprolol and ivabradine, respectively , increased exercise tolerance ≥1 min in the treadmill-test. Ivabradine treatment, in comparison with bisoprolol one, was associated by more expressed increase in chronotropic reserve in treadmill-test (p<0.05) and significant improvement of sensitivity coefficient of brachial artery to tension shift in FMD (p<0.005). In patients with endothelial dysfunction bisoprolol (69.4 %) and ivabradine (52.8%) efficacy did not differ significantly. At the same time in patients with normal endothelial functions increase in exercise tolerance ≥1 min in treadmill-test was observed in 50% (p<0.05) and 20.8% of patients treated with ivabradine and bisoprolol, respectively. Both drugs significantly increased QL, and ivabradine improved erectile function (p<0.005) in comparison with bisoprolol. Conclusion. The If-channel inhibitor ivabradine and beta-blocker bisoprolol have a similar antianginal efficacy in patients with stable angina pectoris. Treatment with ivabradine, in comparison with bisoprolol, was associated with improvement of chronotropic reserve in treadmill-test (p<0.05), sensitivity coefficient of brachial artery to tension shift in FMD test (p<0.005) and erectile function (p<0.005).

About the Authors

R. D. Kurbanov
Republican Specialized Center for Cardiology

A. O. Kan
Republican Specialized Center for Cardiology

F. M. Bekmetova
Republican Specialized Center for Cardiology

A. B. Shek
Republican Specialized Center for Cardiology


1. Kannel W.B., Kannel C., Paffenbarger R.S. et al. Heart rate and cardiovascular mortality: the Framing-ham Study. Am Heart J 1987; 113:1489-1494.

2. Diaz A., Bourassa M.G., Guertin M.C. et al. Long-term prognostic value of resting heart rate in patients with suspected of proven coronary artery disease. Eur Heart J 2005;26:967-974

3. Von Arnim T. Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine. The TIBBS Investigators. J Am Coll Car-diol 1995; 25: 231-238.

4. Von Arnim T. Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up. J Am Coll Cardiol 1996; 28: 20-24.

5. Borer J.D., Fox K., Jaillon P. et al. Antianginal and antiischemic effects of ivabradine, an If inhibitor in stable angina. Circulation 2003;107:817-823.

6. Tardif J.C., Ford I., Tendera M. et al. On behalf of the INITIATIVE study investigators group. Efficacy of ivabradine, a new selective If inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J 2005;26:2529-2536.

7. Fox K., Ford I., Steg P.G. et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomized, double-blind, placebo-controlled trial. Lancet 2008; 372: 807–816.

8. Simon L., Ghaleh B., Puybasset L. et al. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther 1995: 275: 659-666.

9. Drouin A., Gendron M.E., Thorin E. et al. Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br J of Pharmacol 2008; 154: 749-757.

10. Custodis F., Baumhakel M., Schlimmer N. Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in Apolipoprotein E-deficient mice. Circulation 2008; 117: 2377-2387.

11. Asadi-Lari M., Packham C., Gray D. Patientsґs satisfaction and quality of life in coronary artery disease. Health Qual Life Outcomes 2003;1: 57.

12. Asadi-Lari M., Packham C., Gray D. Psychometric properties of a new health needs analysis tool designed for cardiac patients. Public Health 2005; 119: 590-598.

13. The Task Force on Beta-Blockers of the European Society of Cardiology. Expert consensus document on в-adrenergic receptor blockers. Eur Heart J 2004; 25: 1341-1362.

14. Baumhдkel M., Custodis F., Schlimmer N. et al. Heart rate reduction with ivabradine improves erectile dysfunction in parallel to decrease in atherosclerotic plaque load in ApoE-knockout mice. Atherosclerosis 2010;212(1):55-62.

15. Celermajer D.S., Sorensen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111-1115

16. Bernard A., Ducardonnet A., Hoffman O. et al. Exercise Testing in Cardiology. Paris: Springer; 2009.

17. Aronov D.M., Lupanov V.P. Functional tests in cardiology. Moscow: MEDpress-inform; 2007. Russian (Аронов Д.М., Лупанов В.П. Функциональные пробы в кардиологии. М.: МЕДпресс- информ; 2007).

18. Manak N.A., Karpova I.S., Karoza A.E. et al. A differentiated approach to the correction of endothelial dysfunction in patients with stable angina with risk factors for coronary heart disease (hypertension, hypercholesterolemia, smoking). Minsk: Republican Scientific and Practical Center "Cardiology" MOH Rep. Belarus; 2004. Манак Н.А., Карпова И.С., Кароза А.Е. и др. Дифференцированный подход к коррекции эндотелиальной дисфункции у больных стабильной стенокардией с факторами риска ишемической болезни сердца (артериальной гипертензией, гиперхолестеринемией, курением). Минск: Республиканский научно-практический центр «Кардиология» МЗ Респ Беларусь; 2004.

19. Taddei S., Virdis A., Ghiadoni L. et al. Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. Drugs 2002: 62(2): 265–284.

20. Flammer A.J., Hermann F., Wiesli P. et al. Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension. J Hypertens 2007:25(4):785-791.

21. Brehm B.R., Bertsch D., von Fallois J., Wolf S.C. Beta-blockers of the third generation inhibit endothelin-1 liberation, mRNA production and proliferation of human coronary smooth muscle and endothelial cells. J Cardiovasc Pharmacol 2000:36(5 Suppl. 1): S401–S403.

22. Brehm B.R., Wolf S.C., 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): 430–439.

23. Grigor'eva N.Iu., Sharabrin E.G., Kuznetsov A.N. et al. Effects of beta 1-adrenoblocker bisoprolol on endothelial dysfunction in patients with stable angina pectoris in combination with chronic obstructive pulmonary disease. Ter Arkh 2009;81(3):28-31. Russian (Григорьева Н.Ю., Шарабрин Е.Г, Кузнецов А.Н. и др. Влияние бета-1 адреноблокатора бисопролола на эндотелиальную дисфункцию у больных стабильной стенокардией напряжения с хронической обструктивной болезнью лёгких. Тер Архив 2009;3:28-31).

24. Saku K., Liu K., Takeda Y. et al. Effects of lisinopril and bisoprolol on lipoprotein metabolism in patients with mild-to-moderate essential hypertension. Clin Ther 1995: 17(6): 1136-1146.

25. Kukes V.G., Ostroumova O.D., Mamaev V.I. et al. Efficacy and safety of different beta-blockers in patients with isolated systolic hypertension associated with diabetes mellitus and obstructive pulmonary diseases. Ter Arkh 2003;75(8):43-7. Russian (Кукес В.Г., Остроумова О.Д, Мамаев В.И. и др. Эффективность и безопасность различных бета-блокаторов у пациентов с изолированной систолической гипертонией и сопутствующими сахарным диабетом и обструктивными болезнями легких. Тер архив 2003; 75 (8): 43–47).

26. Kosheleva N.A., Rebrov A.P. Dynamics of structural functional parameters of cardiovascular system in patients with Stable Angina and Congestive Heart Failure treated with Ivabradine for six months. Kardiologiia 2010;50(9):34-40. Russian (Кошелева Н.А., Ребров А.П. Динамика структурно-функциональных показателей сердечно-сосудистой системы у больных стабильной стенокардией и хронической сердечной недостаточностью на фоне 6-месячной терапии ивабрадином. Кардиология 2010: 9:34-40).

27. Broekman C.P., Haensel S.M., Van de Ven L.L. et al. Bisoprolol and hypertension: effects on sexual functioning in men. J Sex Marital Ther 1992; 18(4): 325-331.

28. Prisant L.M., Weir M.R., Frishman W.H. et al. Self Reported Sexual Dysfunction in Men and Women Treated With Bisoprolol, Hydrochlorothiazide, Enalapril, Amlodipine, Placebo, or Bisoprolol/Hydrochlorothiazide. J Clin Hypertens (Greenwich) 1999; 1(1): 22-26.

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