Rational Pharmacotherapy in Cardiology

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Arterial hypertension (HT) takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS). Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (pro)renin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

About the Authors

V. V. Popov
Research Clinical Center of JSC "Russian Railways"
Russian Federation

N. A. Bulanov
I.M. Setchenov First Moscow State Medical University
Russian Federation

G. G. Ivanov
I.M. Setchenov First Moscow State Medical University
Russian Federation


1. National guidelines for diagnosis and treatment of hypertension. Kardiovaskulyarnaya Terapiya i Profilaktika 2008; 7(6) suppl 2: 1-31. Russian (Национальные рекомендации по диагностике и лечению артериальной гипертонии. Кардиоваскулярная Терапия и Профилактика 2008; 7(6) Приложение 2: 1-31).

2. Shlyakhto E.V. Hypertensive heart disease. Pathogenesis and progression from the position of neurogenic mechanisms. Kardiovaskulyarnaya Terapiya i Profilaktika 2003; (2): 22-26. Russian (Шляхто Е.В. Гипертоническая болезнь. Патогенез и прогрессирование с позиции нейрогенных механизмов. Кардиоваскулярная Терапия и Профилактика 2003; (2): 22-26).

3. Chazov E.I., Chazova I.E., editors. Guidelines for hypertension. Moscow: Media Medika; 2005. Russian (Чазов Е.И., Чазова И.Е., редакторы. Руководство по артериальной гипертонии. М.: Медиа Медика; 2005).

4. Shlyakhto E.V., Baranova E.I., Bol'shakova O.O. Hypertensive heart disease. Diagnosis and treatment. A Manual for Students 5.6 courses, physicians and medical residents. St. Petersburg: St. Petersburg State Medical University; 2007. Russian (Шляхто Е.В., Баранова Е.И., Большакова О.О. Г ипертоническая болезнь. Диагностика и лечение. Пособие для студентов 5-6 курсов, врачей и клинических ординаторов. Санкт-Петербург: СПбГМУ; 2007).

5. Aram V., Chobanian M.D. The hypertension paradox – more uncontrolled disease despite improved therapy. N Engl J Med 2009; 361: 878-887.

6. 2007 Guidelines for the Management of Arterial Hypertension. Journal of Hypertension 2007; 25: 1105–1187.

7. Wu K.C., Gerstenblith G. Update on Newer Antihypertensive Medicines and Interventions. Journal of Cardiovascular Pharmacology and Therapeutics 2010;15(3):257-267.

8. Unger T. The role of the renin-angiotensinsystem in the development of cardiovascular disease. Am J Cardiol 2002; 89: 3A-9A.

9. Stryuk R.I. The validity of sartanov in hypertensive patients. Sistemnye Gipertenzii 2009; (4): 29-34. Russian (Стрюк Р .И. Обоснованность использования сартанов у больных артериальной гипертонией. Системные Гипертензии 2009; (4): 29-34).

10. Wan Y ., Wallinder C., Plouffe B. et al. Design, synthesis and biological evaluation of the first selective non-peptide AT2 receptor agonist. J Med Chem 2004; 47: 5995-6008.

11. Bosnyak S., Welungoda I.K., Hallberg A. et al. Stimulation of angiotensin AT2 receptors by the non- peptide agonist, Compound 21, evokes vasodepressor effects in conscious spontaneously hypertensive rats. Br J Pharmacol 2010; 159: 709-716.

12. Kaschina E., Grzesiak A., Li J. et al. AT2-receptor stimulation:a novel option of therapeutic interference with the renin-angiotensin-system in myocardial infarction? Circulation 2008; 118: 2523-32.

13. Muscha U. Steckelings, Franziska Rompe, Elena Kaschina et al. The past, present and future of angiotensin II type 2 receptor stimulation. Journal of Renin-Angiotensin-Aldosterone System 2010; 11(1):67-73.

14. Prasad V.S., Palaniswamy C., Frishman W.H. Endothelin as a clinical target in the treatment of systemic hypertension. Cardiol Rev 2009; 17(4): 181-191.

15. Barst R.J., Rich S., Widlitz A. et al. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension: open-label pilot study. Chest 2002; 121: 1860-8.

16. Trenkner J., Preim F ., Bauer C. et al. Endothelin receptor A blockade reduces proteinuria and vascular hypertrophy in spontaneously hypertensive rats on hight-salt diet in a blood-pressure-independent manner . Clin Sci 2002;103:385-8.

17. Cosenzi A., Bernobich E., Bonavita M. et al. Antihypertensive treatment with enrasentan (SB217242) in an animal model ofhypertension and hyperinsulinemia. J Cardiovasc Pharmacol 2002;39:488-95.

18. Krum H., Viskoper R.J., Lacourciere Y . et al. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. N Engl J Med 1998;338:784-90.

19. Nakov R., Pfarr E., Eberle S. Darusentan: an effective endothelin A receptor antagonist for treatment of hypertension. Am J Hypertens 2002;15:583–589.

20. Black H.R., Bakris G.L., Weber M.A. et al. Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, double-blind, placebo-controlled dose-ranging study. J Clin Hypertens (Greenwich) 2007;9(10):760-9.

21. Weber M.A., Black H., Bakris G. et al. A selective endothelinreceptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomized, double-blind, placebo-controlled trial. Lancet 2009;374(9699):1423-1431.

22. Minushkina L.O., Zateyshchikov D.A. Are there any prospects of endothelin receptor antagonists? Farmateka 2003;6:51-58. Russian (Минушкина Л.О., Затейщиков Д.А. Есть ли перспективы у антагонистов рецепторов эндотелина? Фарматека 2003;6:51-58).

23. Martynyuk T .V., Nakonechnikov S.N., Chazova I.E. Endothelin receptor antagonists for pulmonary arterial hypertension: yesterday , today and tomorrow. Rossiyskiy Kardiologicheskiy zhurnal 2009;4:73-

24. Russian (Мартынюк Т .В., Наконечников С.Н., Чазова И.Е. Антагонисты рецепторов эндотелина при легочной артериальной гипертензии: вчера, сегодня и завтра. Российский Кардиологический журнал 2009;4:73-82).

25. Pitt B., Zannad F ., Remme W.J. et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone evaluation Study Investigators. N Engl J Med 1999; 341: 709-717.

26. Minushkina L.O., Zateyshchikov D.A. Eplerenone — a selective aldosterone receptor blocker . Farmateka 2007;138(3):10-17. Russian (Минушкина Л.О., Затейщиков Д.А. Эплеренон — селективный блокатор рецепторов альдостерона. Фарматека 2007;138(3):10-17).

27. White W.B., Duprez D., Hillaire R. et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension 2003;41:1021-1026.

28. Williams G.H., Burgess E., Kolloch R.E. et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol 2004;93:990-996.

29. Weinberger M.H., White W.B., Ruilope L.M. et al. Effects of eplerenone versus losartan in patients with low-renin hypertension. Am Heart J 2005;150:426-433.

30. Pitt B., White H., Nicolau J. et al. for the EPHESUS Investigators. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005;46:425-431.

31. Amar L., Azizi M., Menard J. et al. Aldosterone synthase inhibition with LCI699 a proof-of-concept study in patients with primary aldosteronism. Hypertension 2010;56:831.

32. Menard J., Watson C., Rebello S. Hormonaland and electrolyte responses to the aldosterone synthase inhibitor LCI699 in sodium depleted healthy. JACC 2010;55:I.10A.

33. White W.B., Calhoun D.A., Krum H. Blockade of aldosterone production as a novel approach to the management of high blood pressure: efficacy and tolerability of the aldosterone synthase inhibitor LCI699 in patients with stage 1-2 hypertension. JACC 2010;55;A61.E585.

34. Fiebeler A., Nussberger J., Shagdarsuren E. et al. Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage. Circulation 2005;111:3087-3094.

35. Lea W.B., Kwak E.S., Luther J.M. et al. Aldosterone antagonism or synthase inhibition reduces endorgan damage induced by treatment with angiotensin and high salt. Kidney Int 2009;75:936-944.

36. Graul A.I., Revel L., Rosa E., Cruces E. Overcoming the obstacles in the pharma/biotech industry: 2008 Update. Drug News Perspect 2009; 22(1): 39

37. Berezin A.E. Cyrene — direct renin inhibitors — a new class of drugs. The potential for clinical application. Ukr Med Chasopis 2009;6(74):58-65. Ukrainian (Березин А.Е. Кирены — прямые ингибиторы ренина — новый класс лекарственных средств. Потенциальные возможности клинического применения. Укр Мед Часопис 2009;6(74):58-65).

38. Azizi M., Menard J., Bissery A. et al. Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1-receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J Am Soc Nephrol 2004;15: 3126-33.

39. Shestakova M.V., Kutyrina I.M. The first direct renin inhibitor aliskiren: New Perspectives nefroprotektsii diabetes. Consilium Medicum 2009;11(12):61-66. Russian (Шестакова М.В., Кутырина И.М. Первый прямой ингибитор ренина алискирен: новые перспективы нефропротекции при сахарном диабете. Consilium Medicum 2009;11(12):61-66).

40. Wood J.M., Maibaum J., Rahuel J. et al. Structure-based design of aliskiren, a novel orally effective renin inhibitor . Biochem Biophys Res Commun 2003;308:698-705.

41. Villamil A., Chrysant S., Calhoun D. et al. The novel renin inhibitor aliskiren provides effective blood pressure control in patients with hypertension when used alone or in combination with hy- drochlorothiazide. J Clin Hypertens 2006;8:100.

42. Tuttle K.R. Could renin inhibition be the next step forward in the treatment of diabetic kidney disease? Nat Clin Pract Endocrinol Metab 2009;5(1):20-1

43. Solomon S.D., Appelbaum E., Manning W.J. et al. Effect of the direct Renin inhibitor aliskiren, the Angiotensin receptor blocker losartan, or both on left ventricular mass in patients with hypertension and left ventricular hypertrophy. Circulation 2009;119(4):530-7

44. Parving H.H., Persson F ., Lewis J.B. et al. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med 2008;358(23):2433–2446.

45. Solomon S.D., Shin S.H., Shah A. Effect of the direct renin inhibitor aliskiren on left ventricular remodeling following myocardial infarction with systolic dysfunction. Eur Heart J 2011;32(10):1227-34.

46. Parving H.H., Brenner B.M., McMurray J.J. et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant 2009;24(5): 1663-71

47. Chazova I.E., Fomin V.V., Razuvaeva M.A. Direct renin inhibitor aliskiren — an innovative strategy for antihypertensive therapy. Consilium Medicum 2009;11(1):9-14. Russian (Чазова И.Е., Фомин В.В., Разуваева М.А. Прямой ингибитор ренина алискирен — инновационная стратегия антигипертензивной терапии. Consilium Medicum 2009;11(1):9-14).

48. Mukhin N.A., Fomin V.V. Plasma renin activity — an independent risk factor and target of antihypertensive therapy: the role of aliskiren. Consilium Medicum Ukraina 2010;(7):38-45. Russian (Мухин Н.А., Фомин В.В. Активность ренина плазмы — фактор риска и самостоятельная мишень антигипертензивной терапии: роль алискирена. Consilium Medicum Ukraina 2010;(7):38-45).

For citation:

Popov V.V., Bulanov N.A., Ivanov G.G. CURRENT TARGET OF ANTIHYPERTENSIVE THERAPY. DATA FROM CLINICAL TRIALS. PART 1. Rational Pharmacotherapy in Cardiology. 2012;8(1):88-94. (In Russ.)

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