Triple combination - a new approach to the treatment of metabolic syndrome

Objective. To investigate efficacy of combination therapy including I1-imidazoline receptor agonist, angiotensin receptor blocker, and thiazide diuretic in metabolic syndrome (MS). Design and methods. We investigated 34 patients (mean age 52,3 ± 6,7 years old, mean systolic blood pressure (ВР) 175 ± 21,0 mmHg, mean diastolic BP 102,4 ± 10,5 mmHg) with MS. Blood tests for serum lipids, plasma renin activity, aldosterone, immunoreactive insulin, and leptin, peroral glucose tolerance test, semiquantitative test for microalbuminuria, 24-hour ECG-monitoring for heart rate variability (HRV) analysis were performed. All patients were treated with moxonidine 200 mg per day, and combination of eprosartan 600 mg/day with hydrochlorothiazide 12,5 mg/day for 18-week period. Results. After 18 weeks target BP levels were achieved in 88 % of the patients. HRV analysis demonstrated increase of the total power, decrease of sympathetic (low frequency [LF n.u.] and low to high frequency ration - LF/HF), humoral and metabolic (% VLF), and increase of parasympathetic parameters (HF n.u. and % HF) (р < 0,05). We found a decrease of triglyceride levels, increase of high-density lipoprotein levels, and decline of percentage of patients with microalbuminuria (р < 0,05). Aldosterone, leptin, and immunoreactive insulin levels were lower compared to basic levels (р < 0,05). Conclusion. Three-component therapy of MS with eprosartan, hydrochlorothiazide, and moxonidine provides high antihypertensive and metabolic efficacy, affecting the majority of the pathological mechanisms.

metabolic syndrome, eprosartan, moxonidine, hydrochlorothiazide

1. Guidelines for the Management of Arterial Hypertension The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // J. Hypertens. - 2007. - Vol. 25, № 6. - P. 1105-1187.

2.

3. Lakka H.-M., Laaksonen D.E., Lakka T.A. et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men // J. Am. Med. Assoc. - 2002. - Vol. 288, № 21. - P. 2709-2716. 3.

4.

5. Диагностика и лечение артериальной гипертензии. Российские рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов (третий пересмотр) // Кардиоваск. терапия. Профилактика. - 2008 - Т. 7, № 6, прил. 2. - С. 1-32.

6.

7. Chobaniam A.V., Bakris G.L., Black H.R. et al. The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of the high blood pressure. The JNC 7 Report // J. Am. Med. Assoc. - 2003. - Vol. 289, № 19. - P. 2560-2572. 5.

8.

9. American Diabetes Association. Treatment of hypertension in adults with diabetes // Diabetes Care. - 2003. - Vol. 26, suppl. 1. - P. S80-S82. 6.

10.

11. National Kidney Foundation Guideline. KDOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative // Am. J. Kidney Dis. - 2002. - Vol. 39, suppl. 2. - P. S1-S246.

12.

13. Morse S.A., Zhang R., Thakur V. et al. Hypertension and metabolic syndrome // Am. J. Med. Sci. - 2005. - Vol. 330, № 6. - P. 303-310.

14.

15. Elliott W.J., Meyer P.M. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis // Lancet. - 2007. - Vol. 369, № 9572. - P. 201-207.

16.

17. Waters J., Ashford J., Jager B. et al. Use of moxonidine as initial therapy and in combination in the treatment of essential hypertension: results of the TOPIC (Trial Of Physiotens In Combination) study // J. Clin. Basic Cardiol. - 1999. - Vol. 2, № 2. - Р. 219-224.

18.

19. Sharma A.M., Wagner T., Marsalek P. Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study // J. Hum. Hypertens. - 2004. - Vol. 18, № 9. - P. 669-675.

20.

21. Derosa G., Cicero A.F., D'Angelo A. et al. Metabolic and antihypertensive effects of moxonidine and moxonidine plus irbesartan in patients with type 2 diabetes mellitus and mild hypertension: a sequential, randomized, double-blind clinical trial // Clin. Ther. - 2007. - Vol. 29, № 4. - Р. 602-610.

22.

23. Neumann J., Ligtenberg G., Oey L. et al. Moxonidine normalizes sympathetic hyperactivity in patients with eprosartan-treated chronic renal failure // J. Am. Soc. Nephrol. - 2004. - Vol. 15, № 11. - Р. 2902-2907.

24.

25. Alberti K.G., Zimmet P.Z., Shaw J.E. The metabolic syndrome - a new worldwide definition from the International Diabetes Federation Consensus // Lancet. - 2005. - Vol. 366, № 9491. - P. 1059-1062.

26.

27. Мильто А.С., Толкачева В.В., Кобалава Ж.Д. Моксонидин в комбинированной терапии гипертонической болезни с высоким риском сердечно-сосудистых осложнений // Клинич. фармакол. Терапия. - 2001. - Т. 4. - С. 18-23.

28.

29. Шадчнева Н.А. Изменение спектральных характеристик вариабельности ритма сердца у больных с вентральными грыжами при применении моксонидина // Украинский кардиол. журн. - 2009. - № 2. - С. 48-52.

30.

31. Diсkstein K., Manhenke C., Aarsland T., McNay J., Wiltse C., Wright T. The effect of chronic, sustained-release moxonidine therapy on clinical and neurohumoral status in patients with heart failure // Int. J. Cardiol. - 2000. - Vol. 75, № 2-3. - P. 167-176.

32.

33. Jacob S., Klimm H.J., Rett K. et al. Effects of moxonidine vs. metoprolol on blood pressure and metabolic control in hypertensive subjects with type 2 diabetes // Exp. Clin. Endocrinol. Diabetes. - 2004. - Vol. 112, № 6. - P. 315-322.

34.

35. Sanjuliani A.F., Francischetti E.A., Genelhu de Abreu V., Ueleres Braga J. Effects of moxonidine on the sympathetic nervous system, blood pressure, plasma renin activity, plasma aldosterone, leptin, and metabolic profile in obese hypertensive patients // J. Clin. Bas. Cardiol. - 2004. - Vol. 7, № 1-4. - P. 19-25.

36.

37. Haenni A., Lithell H. Moxonidin improves insulin sensivity in insulin-resistance hypertensives // J. Hypertens. - 1999. - Vol. 17, suppl. 3. - P. S29-S35.

38.

39. Чазова И.Е., Мычка В.Б. Новые возможности в лечении больных с метаболическим синдромом (результаты исследования ALMAZ) // Сonsilium Medicum. Прил. Системные гипертензии. - 2006. - № 2. - С. 14-18.

40.

41. Мананко Е.И., Воробьева Е.В., Калашникова Т.П. и др. Эффективность комбинаций эналаприла с нифедипином пролонгированного действия и моксонидином у больных артериальной гипертонией с метаболическим синдромом // Клинич. мед. - 2008. - Т. 86, № 7. - С. 56-61.

42.

43. Chazova I., Almazov V.A., Shlyakhto E. Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin // Diabetes Obes. Metab. - 2006. - Vol. 8, № 4. - P. 456-465.

44.

45. Куликов А.Ю. Фармакоэкономический анализ использования физиотенза у пациентов с артериальной гипертонией, избыточным весом и сахарным диабетом второго типа // Фармакоэкономика. - 2009. - № 1. - С. 19-23.

46.

47. Kirch W., Hutt H.K., Planitz V. Pharmacodynamic action and pharmacokinetics of moxonidine after single oral administration in hypertensive patients // J. Clin. Pharmacol. - 1990. - Vol. 30, № 12. - Р. 1088-1095.

48.

49. Mitrovic V., Patyna W., Huting J. et al. Hemodynamic and neurohumoral effects of moxonidine in patients with essential hypertension // Cardiovasc. Drugs Ther. - 1991. - Vol. 5, № 6. -Р. 967-972.

50.

51. Lewis E.J., Hunsicker L.G., Bain R.P., Rohde R.D. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The Collaborative Study Group // N. Engl. J. Med. - 1993. - Vol. 329, № 20. - P. 1456-1462.

52.

53. Brenner B.M., Cooper M.F., de Zeeuw D. et al. Effects of losartan on renal and cardio-vascular outcomes in patients with type 2 diabetes and nephropathy // N. Engl. J. Med. - 2001. - Vol. 345, № 12. - P. 861-869.

54.

55. Lewis E.J., Hunsicker L.G., Clarke W.R. et al. Renoprotective effect of the angiotensin-receptor antagonist, irbesartan in patients with nephropathy due to type 2 diabetes // N. Engl. J. Med. - 2001. - Vol. 345, № 12. - P. 851-860.

56.

57. Strojek K., Grzeszczak W., Gorska J., Leschinger M.I., Ritz E. Lowering of microalbuminuria in diabetic patients by sympathoplegic agent: novel approach to prevent progression of diabetic nephropathy // J. Am. Soc. Nephrol. - 2001. - Vol. 12, № 3. - P. 602-605.

58.

59. Krespi P.G., Makris T.K., Hatzizacharias A.N. et al. Moxonidine effect on microalbuminuria, thrombomodulin, and plasminogen activator inhibitor-1 level in patient with essential hypertension. // Cardivasc. Drugs Ther. - 1998. - Vol. 12, № 5. - P. 463-467.