Russian Heart Failure Journal 2010year Ivabradine as an alternative to beta-blockers in treatment of chronic heart failure FC III

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Ivabradine as an alternative to beta-blockers in treatment of chronic heart failure FC III

Kanorsky S. G., Tregubov V. G., Kumacheva E. S., Pokrovskiy V. M.

Keywords: ivabradine, metoprolol succinate, regulatory and adaptive status, cardio-respiratory synchronicity, CHF

DOI: 10.18087/rhfj.2010.6.1421

Urgency. Chronic heart failure is common, serious, unfavorable consequence of all cardiovascular disease. β-blockers (BB) usage in patients with CHF can be limited due to their negative effect on bronchus, peripheral blood vessels and erectile function, presence of bradycardia, hypertension, severe systolic dysfunction. This justifies the use of drugs that control heart rate, have positive effect on target organs, do not impair the functional organism state – the capacity for regulation and adaptation. For objective quantitative assessment of regulatory and adaptive status (RAS) a test of cardio-respiratory synchronization (SDS) was proposed, taking into account the interaction between two most important functions of vegetative supply – cardiac and respiratory. Aim. To determine the efficacy of combined treatment with ivabradine of CHF FC III and CAD and / or essential hypertension (EH) III stage, by assessment of RAS. In such cases an inhibitor of If -channel ivabradine can be an alternative to BB. Materials and methods. The study included 100 patients with CHF FC III and CAD and / or EH III stage, randomized into two groups of combined therapy. The first group (56 patients aged 62.9±1.8 years) received metoprolol succinate sustained-release (the average dose 59.1±4.5 mg / day). The second group (44 patients aged 59.4±1.3 years) received If -channel inhibitor ivabradine (the average dose 12.1±2.3 mg / day) in case of impossibility to use BB. At baseline and after 6 months further examination was performed: treadmill test with estimation of maximal oxygen consumption under load (VO2 max), echocardiography, ambulatory blood pressure monitoring, 6 min walk test, blood level of NT-proBNP, RAS test. Results. Therapy with ivabradine improved structural and functional myocardial state, increased exercise tolerance, caused positive dynamics in NT-proBNP plasma levels, VO2 max, and RAS test. Thus, ivabradine can probably serve as an alternative to BB in case of impossibility of their use in patients with CHF FC III, including patients with decreased LVEF.
  1. Dickstein K, Kjekshus J; OPTIMAAL Steering Committee of the OPTIMAAL Study Group. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet. 2002;360 (9335):752–760.
  2. Сторожаков Г. И., Гендлин Г. Е. Основные направления в лечении больных с хронической сердечной недостаточностью (руководст­во для врачей терапевтов врачей общей практики). – М.: Миклош. 2008. – 312 с.
  3. Fox K, Ford I, Steg PG 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 (9641):807–816.
  4. DiFrancesco D, Camm J. Heart rat lowering by specific and selective If current inhibition with ivabradine. A new therapeutc in cardiovascular disease. Drugs. 2004;64 (16):1757–1765.
  5. Cooney MT, Vartiainen E, Laatikainen T et al. Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. Am Heart J. 2010;159 (4):612–619.
  6. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357 (9266):1385–1390.
  7. Lopez-Sendon J, Swedberg K, McMurray J et al. Expert consensus document on beta-adrenergic receptor blockers. Eur Heart J. 2004;25 (15):1341–1362.
  8. Heusch G, Schulz R. The role of heart rate and the benetits of heart rate reduction in acute myocardial ishemia. Eur Heart J. 2007; (Suppl F): F8‑F14.
  9. De Ferrari GM, Mazzuero A, Agnesina L et al. Ivabradine infusion in patiens with severe heart failure is safe, reduces heart rate and increases left ventricular stroke volume and systolic work. Eur Heart J. 2006;27: (Suppl):Abstract 330.
  10. 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):1674–1679.
  11. Покровский В. М. Воспроизведение сердцем ритма сигналов, сформированных в центральной нервной системе. Формирование ритма сердца в организме человека и животных. – Краснодар: Кубань-Книга. 2007. – С. 61–71.
  12. Покровский В. М., Пономарев В. В., Артюшков В. В. и др. Система для определения сердечно-дыхательного синхронизма у человека. Россия, патент № 86860, 2009.
  13. Покровский В. М. Сердечно-дыхательный синхронизм – метод количественной интегративной оценки регуляторно-адаптивного статуса (состояния) организма. Сердечно-дыхательный синхронизм в оценке регуляторно-адаптивных возможностей организма. – Краснодар: Кубань-Книга. 2010. – С. 183–185.
  14. Ерофеева С. Б., Манешина О. А., Белоусов Ю. Б. Место ивабрадина – первого If -ингибитора избирательного и специфического действия, в лечении сердечно-сосудистых заболеваний. Качественная клиниче­ская практика. 2006;1:10–22.
  15. Покровский В. М., Потягайло Е. Г., Абушкевич В. Г. и др. Сердечно-дыхательный синхронизм: выявление у человека, зависимость от свойств нервной системы и функциональных состояний организма. Успехи физиологических наук. 2003;3:68–77.
  16. Couvreur N, Tissier R, Pons S et al. Chronic heart rate reduction with ivabradine improves systolic function of the reperfused heart through a dual mechanism involving a direct mechanical effect and a long-term increase in FKBP12 / 12.6 expression. Eur Heart J. 2010;31 (12):1529–1537.
  17. Zhang RL, Christensen LP, Tomanek RJ. Chronic heart rate reduction facilitates cardiomyocyte survival after myocardial infarction. Anat Rec. (Hoboken). 2010;293 (5):839–848.
Kanorsky S. G., Tregubov V. G., Kumacheva E. S. et al. Ivabradine as an alternative to beta-blockers in treatment of chronic heart failure FC III. Russian Heart Failure Journal. 2010;11(6):368-371.

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