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Central pressure and arterial stiffness in patients with stable angina and arterial hypertension without left ventricular systolic dysfunction: effects of atenolol and ivabradine

Shavarov A. A., Kiyakbaev G. K., Kobalava Zh. D.
Federal State Autonomous Educational Institution of Higher Education, "Russian University of Peoples' Friendship", Miklukho-Maklaya 6, Moscow 117198

Keywords: ivabradine, atenolol, exertional angina, arterial stiffness, central arterial pressure, augmentation index

DOI: 10.18087/rhfj.2015.3.2101

Background. High heart rate (HR) is considered an important cause of increased arterial stiffness. Due to great wave reflections induced by bradycardia, decreasing HR with pulse-slowing drugs prevents the desirable decrease in aortic BP. This may be clinically important for IHD patients with AH, where a physician should aim at achieving the target HR of 55–60 bpm. Aim. To compare effects of ivabradine and atenolol on parameters of arterial stiffness and central hemodynamics in patients with exertional angina and AH without a history of MI or LV systolic dysfunction. Materials and methods. This open, randomized, prospective study included 31 patients (males, 57 %) aged 61 with FC II–III stable angina, AH and sinus rhythm. 15 patients were randomized to the ivabradine (I) 10 mg / day treatment group and another 16 patients – to the atenolol (A) 50 mg / day treatment group. Drug doses were up-titrated to the target HR of 55–60 bpm for two weeks and remained unchanged after that. A treadmill test, EchoCG, and applanation tonometry were performed for all patients. Results. Atenolol, as distinct from ivabradine, reduced BP measured on the brachial artery and did not change the central augmentation index, which was associated with prolongation of LV systole. Ivabradine, in contrast, reduced the central augmentation index and did not significantly influence the duration of LV systole. With comparable decreases in HR, ivabradine, like atenolol, slowed the pulse wave propagation velocity (by 1.5 and 1.6 m / sec, р=0.002 for both). Results of the treadmill test were comparable in both groups. Conclusion. Ivabradine, like atenolol, slowed the pulse wave propagation velocity in AH patients with stable angina without LV systolic dysfunction. Without affecting peripheral BP, ivabradine, like atenolol, reduced aortic BP. This effect was probably due to the ivabradine capability for decreasing the central augmentation index.
  1. Blacher J., Guerin A.P., Pannier B., Marchais S.J., Safar M.E., London G.M. Impact of aortic stiffness on survival in end-stage renal disease. Circulation. 1999;99 (18):2434–2439.
  2. Laurent S., Boutouyrie P., Asmar R., Gautier I., Laloux B., Guize L., et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001;37 (5):1236–1241.
  3. Cruickshank K., Riste L., Anderson S.G., Wright J.S., Dunn G., Gosling R.G. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106 (16):2085–2090.
  4. Орлова Я.А., Макарова Г.В., Яровая Е.Б., Нуралиев Э.Ю., Агеев Ф.Т. Прогностическое значение различных параметров артериальной жесткости при ИБС. Сердце. 2009;8 (2):98–103.
  5. Stefanadis C., Dernellis J., Tsiamis E., Stratos C., Diamantopoulos L., Michaelides A., et al. Aortic stiffness as a risk factor for recurrent acute coronary events in patients with ischaemic heart disease. Eur. Heart J. 2000;21 (5):390–396.
  6. Roman M.J., Devereux R.B., Kizer J.R., Lee E.T., Galloway J.M., Ali T., et al. Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension. 2007;50 (1):197–203.
  7. Pini R., Cavallini M.C., Palmieri V., Marchionni N., Di Bari M., Devereux R.B., et al. Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population: the ICARe Dicomano Study. J. Am. Coll. Cardiol. 2008;51 (25):2432–2439.
  8. Williams B., Lacy P.S., Thom S.M., Cruickshank K., Stanton A., Collier D., et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113 (9):1213–1225.
  9. Jankowski P., Kawecka-Jaszcz K., Czarnecka D., Brzozowska-Kiszka M., Styczkiewicz K., Loster M., et al. Pulsatile but not steady component of blood pressure predicts cardiovascular events in coronary patients. Hypertension. 2008;51 (4):848–855.
  10. Safar M.E., Blacher J., Pannier B., Guerin A.P., Marchais S.J., Guyonvarc’h P.-M., et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39 (3):735–738.
  11. Williams B., Lacy P.S. Central aortic pressure and clinical outcomes. J. Hypertens. 2009;27 (6):1123–1125.
  12. Vlachopoulos C., Aznaouridis K., O’Rourke M.F., Safar M.E., Baou K., Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur. Heart J. 2010;31 (15):1865–1871.
  13. Mulder P., Barbier S., Chagraoui A., Richard V., Henry J.P., Lallemand F., 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):1674–1679.
  14. Jondeau G., Korewicki J., Vasiliauskas D. Effect of ivabradine in patients with left ventricular systolic dysfunction and coronary artery disease. Eur Heart J Suppl. (25):451.
  15. Heidland U.E., Strauer B.E. Left ventricular muscle mass and elevated heart rate are associated with coronary plaque disruption. Circulation. 2001;104 (13):1477–1482.
  16. Giannattasio C., Vincenti A., Failla M., Capra A., Cirò A., De Ceglia S., et al. Effects of heart rate changes on arterial distensibility in humans. Hypertension. 2003;42 (3):253–256.
  17. Sa Cunha R., Pannier B., Benetos A., Siché J.P., London G.M., Mallion J.M., et al. Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects. J. Hypertens. 1997;15 (12 Pt 1):1423–1430.
  18. Asmar R., Topouchian J., Pannier B., Benetos A., Safar M., Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study. Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study. J. Hypertens. 2001;19 (4):813–818.
  19. Copie X., Hnatkova K., Staunton A., Fei L., Camm A.J., Malik M. Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study. J. Am. Coll. Cardiol. 1996;27 (2):270–276.
  20. Benetos A., Rudnichi A., Thomas F., Safar M., Guize L. Influence of heart rate on mortality in a French population: role of age, gender, and blood pressure. Hypertension. 1999;33 (1):44–52.
  21. Gillman M.W., Kannel W.B., Belanger A., Agostino R.B. D’. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am. Heart J. 1993;125 (4):1148–1154.
  22. Diaz A., Bourassa M.G., Guertin M.-C., Tardif J.-C. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur. Heart J. 2005;26 (10):967–974.
  23. Palatini P. Heart rate: a strong predictor of mortality in subjects with coronary artery disease. Eur. Heart J. 2005;26 (10):943–945.
  24. Pocock S.J., Wang D., Pfeffer M.A., Yusuf S., McMurray J.J.V., Swedberg K.B., et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur. Heart J. 2006;27 (1):65–75.
  25. Fox K., Ford I., Steg P.G., Tendera M., Robertson M., Ferrari R., et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet. 2008;372 (9641):817–821.
  26. Cucherat M. Quantitative relationship between resting heart rate reduction and magnitude of clinical benefits in post-myocardial infarction: a meta-regression of randomized clinical trials. Eur. Heart J. 2007;28 (24):3012–3019.
  27. Lechat P., Hulot J.S., Escolano S., Mallet A., Leizorovicz A., Werhlen-Grandjean M., et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001;103 (10):1428–1433.
  28. McAlister F.A., Wiebe N., Ezekowitz J.A., Leung A.A., Armstrong P.W. Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. Ann. Intern. Med. 2009;150 (11):784–794.
  29. Van Bortel L.M., Struijker-Boudier H.A., Safar M.E. Pulse pressure, arterial stiffness, and drug treatment of hypertension. Hypertension. 2001;38 (4):914–921.
  30. Law M.R., Morris J.K., Wald N.J. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
  31. Диагностика и лечение стабильной стенокардии. Российские рекомендации (второй пересмотр). Кардиоваскулярная терапия и профилактика. 6(приложение 4):3–40.
  32. Palatini P., Benetos A., Grassi G., Julius S., Kjeldsen S.E., Mancia G., et al. Identification and management of the hypertensive patient with elevated heart rate: statement of a European Society of Hypertension Consensus Meeting. J. Hypertens. 2006;24 (4):603–610.
  33. López-Bescós L., Filipova S., Martos R. Long-term safety and efficacy of ivabradine in patients with chronic stable angina. Cardiology. 2007;108 (4):387–396.
  34. Tardif J.-C., Ford I., Tendera M., Bourassa M.G., Fox K., INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur. Heart J. 2005;26 (23):2529–2536.
  35. Tardif J.-C., Ponikowski P., Kahan T., ASSOCIATE Study Investigators. Efficacy of the I(f) current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial. Eur. Heart J. 2009;30 (5):540–548.
  36. Custodis F., Baumhäkel M., Schlimmer N., List F., Gensch C., Böhm M., 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):2377–2387.
  37. Tardif J.-C., Grégoire J., Lallier P.L., Joyal M. Chronic heart rate reduction with ivabradine andprevention of atherosclerosis progressionassessed using intravascular ultrasound. Eur Heart J. 5 (5 (Supplement G)):G46—G51.
  38. Thollon C., Vilaine J.-P. I(f) inhibition in cardiovascular diseases. Adv. Pharmacol. 2010;5953–92.
  39. Laurent S., Cockcroft J., Van Bortel L., Boutouyrie P., Giannattasio C., Hayoz D., et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur. Heart J. 2006;27 (21):2588–2605.
  40. Chirinos J.A., Zambrano J.P., Chakko S., Veerani A., Schob A., Willens H.J., et al. Aortic pressure augmentation predicts adverse cardiovascular events in patients with established coronary artery disease. Hypertension. 2005;45 (5):980–985.
  41. Guerin A.P., Blacher J., Pannier B., Marchais S.J., Safar M.E., London G.M. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001;103 (7):987–992.
  42. London G.M., Asmar R.G., O’Rourke M.F., Safar M.E., REASON Project Investigators. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J. Am. Coll. Cardiol. 2004;43 (1):92–99.
  43. Boutouyrie P., Achouba A., Trunet P., Laurent S., EXPLOR Trialist Group. Amlodipine-valsartan combination decreases central systolic blood pressure more effectively than the amlodipine-atenolol combination: the EXPLOR study. Hypertension. 2010;55 (6):1314–1322.
  44. Borer J.S., Fox K., Jaillon P., Lerebours G., Ivabradine Investigators Group. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107 (6):817–823.
  45. Drouin A., Gendron M.-E., Thorin E., Gillis M.-A., Mahlberg-Gaudin F., Tardif J.-C. Chronic heart rate reduction by ivabradine prevents endothelial dysfunction in dyslipidaemic mice. Br. J. Pharmacol. 2008;154 (4):749–757.
  46. Schiffrin E.L. Remodeling of resistance arteries in essential hypertension and effects of antihypertensive treatment. Am. J. Hypertens. 2004;17 (12 Pt 1):1192–1200.
  47. Burns J., Mary D.A.S.G., Mackintosh A.F., Ball S.G., Greenwood J.P. Arterial pressure lowering effect of chronic atenolol therapy in hypertension and vasoconstrictor sympathetic drive. Hypertension. 2004;44 (4):454–458.
  48. Colin P., Ghaleh B., Monnet X., Su J., Hittinger L., Giudicelli J.-F., et al. Contributions of heart rate and contractility to myocardial oxygen balance during exercise. Am. J. Physiol. Heart Circ. Physiol. 2003;284 (2):H676–H682.
Shavarov A. A., Kiyakbaev G. K., Kobalava Zh. D. Central pressure and arterial stiffness in patients with stable angina and arterial hypertension without left ventricular systolic dysfunction: effects of atenolol and ivabradine. Russian Heart Failure Journal. 2015;16 (3):179–186

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