ASSESSMENT OF THE CHANGES IN BLOOD PRESSURE CIRCADIAN PROFILE AND VARIABILITY IN PATIENTS WITH CHRONIC HEART FAILURE AND ARTERIAL HYPERTENSION DURING COMBINED THERAPY INCLUDING IVABRADINE

Aim. To assess the changes in blood pressure (BP) circadian profile and variability in patients with chronic heart failure (CHF) of ischemic etiology and arterial hypertension (HT) due to the complex therapy including ivabradine. Material and methods. Patients (n=90) with CHF class II–III NYHA associated with stable angina II-III class and HT were examined. The patients were randomized into 3 groups depending on received drugs: perindopril and ivabradine - group 1; perindopril, bisoprolol and ivabradine - group 2; perindopril and bisoprolol - group 3. The duration of therapy was 6 months. Ambulatory BP monitoring (ABPM) was assessed at baseline and after treatment. Results. More significant reduction in average 24-hours systolic BP was found in groups 1 and 2 compared to group 3 (Δ%: -19.4±0,4; -21.1±0.4 and -11.8±0.6, respectively) as well as diastolic BP (Δ%: -10.6±0.6; -12.9±0.4 and -4,3±0.3, respectively) and other ABPM indicators. Improvement of BP circadian rhythm was found due to increase in the number of «Dipper» patients (p=0.016). More significant reduction in average daily and night systolic and diastolic BP (p=0.001), as well as daily and night BP variability (p=0.001) was also found in patients of group 2 compared to these of group 1. Conclusion. Moderate antihypertensive effect (in respect of both diastolic and systolic BP) was shown when ivabradine was included into the complex therapy of patients with ischemic CHF and HT. The effect was more pronounced when ivabradine was combined with perindopril and bisoprolol. This was accompanied by reduction in high BP daily variability and improvement of the BP circadian rhythm.

1. Fomin I.V. Epidemiology of heart failure in the European part of the Russian Federation. In: Ageev F.T., Arutyunov G.P., Belenkov Y.N. et al. Chronic heart failure. Moscow: GEOTAR Media; 2010: 7–76. Russian (Фомин И.В. Эпидемиология хронической сердечной недостаточности в Европейской части Российской Федерации. В: Агеев Ф.Т., Арутюнов Г.П., Беленков Ю.Н. и др. Хроническая сердечная недостаточность. М.: ГЭОТАР Медиа; 2010: 7–76).

2. Lee D.S., Ghosh N., Floras J.S. et al. Association of blood pressure at hospital discharge with mortality in patients diagnosed with heart failure. Circ Heart Fail 2009;2(6):616–23.

3. Shin J., Kline S., Moore M. et al. Association of diurnal blood pressure pattern with risk of hospitalization or dearth in men with heart failure. J Card Fail 2007;13(8):656–62.

4. Fox K., Ford I., Steg P.G. et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:807–16.

5. Swedberg K., Komajda M., Bеhm M. et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376(9744):875–85.

6. Mulder P., Barbier S., Chagraoui A. et al. Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation 2004;109(13):1674–9.

7. Kröller-Schön S., Schulz E., Wenzel P. et al. Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress. Basic Res Cardiol 2011;106(6):1147–58.

8. Albaladejo P., Challande P., Kakou A. et al. Selective reduction of heart rate by ivabradine: effect on the visco-elastic arterial properties in rats. J Hypertens 2004;22(9):1739–45.

9. Riccioni G. Ivabradine: from molecular basis to clinical effectiveness. Adv Ther 2010;27(3):160–7.

10. Borer J.S., Le Heuzey J.Y. Characterization of the heart rate-lowering action of ivabradine, a selective I(f) current inhibitor. Am J Ther 2008;15(5):461–73.

11. National guidelines for diagnosis and treatment of chronic heart failure. Serdechnaya Nedostatochnost' 2010; 11(1): 3–62. Russian (Национальные рекомендации по диагностике и лечению хронической сердечной недостаточности. Сердечная Недостаточность 2010; 11(1): 3–62).

12. Nichols W.W., O’Rourke M.F. McDonald’s blood flow in arteries. – 4th ed. – London: Arnold, 1998, 564 pages

13. Panagiotakos D.B., Kromhout D., Menotti A. et al. The relation between pulse pressure and cardiovascular mortality in 12,763 middle-aged men from various parts of the world: a 25-year follow-up of the seven countries study. Arch Intern Med 2005;165:2142–7.

14. Blacher J., Staessen J.A., Girerd X. et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med 2000;160:1085–9.

15. Gibelin P., Spillner E., Bonnan S., Chevallier T. Non-invasive blood pressure variability in chronic heart failure: characteristics and prognostic value. Arch Mal Coeur Vaiss 2003;96(10):955–62.

16. Hoshide S., Kario K., Hoshide Y. et al. Associations between nondipping of nocturnal blood pressure decrease and cardiovascular target organ damage in strinctly selected community-dwelling normotensives. Am J Hypertens 2003;16(6):434–8.

17. Ingellson E., Bjorklund-Bodegard K., Lind L. et al. Diurnal blood pressure pattern and risk of congestive heart failure. JAMA 2006;295(24):2859–66.

18. Benetos A., Rudnichi A., Thomas F. et al. Influence of heart rate on mortality in a French population: role of age, gender and blood pressure. Hypertension 1999;33:44–52.

19. Gilman M., Kannel W., Belanger A., D'Agostino R. Influence of heart rate on mortality among persons with hypertension. The Framingham study. Am Heart J 1993;125:1148–54.

20. Ulu N., Henning R.H., Goris M. et al. Effects of ivabradine and metoprolol on cardiac angiogenesis and endothelial dysfunction in rats with heart failure. J Cardiovasc Pharmacol 2009;53(1):9–17.

21. Milliez P., Messaoudi S., Nehme J. et al. Beneficial effects of delayed ivabradine treatment on cardiac anatomical and electrical remodeling in rat severe chronic heart failure. Am J Physiol Heart Circ Physiol 2009;296(2):435–41.

22. Custodis F., Baumhäkel M., Schlimmer N. et al. Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice. Circulation 2008;117(18):2377–87.

23. Drouin A., Gendron M.E., Thorin E. et al. Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br J Pharmacol 2008;154(4):749–57.