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Optimization of Pharmacotherapy Within the Framework of a Patient-oriented Approach in the Treatment of Hypertension in Multimorbidity Patients (Clinical Case and Literature Review)

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Arterial hypertension (AH) remains one of the main causes of disability and death worldwide, including in Russia. At the same time, the risks of coronary and cerebrovascular events increase in the presence of additional risk factors. The most common modifiable risk factors are metabolic disorders, including pre-diabetes, dyslipidemia, peripheral arterial atherosclerosis, and obesity, which also imposes certain features on the choice of optimal pharmacotherapy. Currently, the terminology of comorbid conditions continues to be discussed depending on their pathogenesis and the presence or absence of dominance of one disease over others, i.e. polymorbidity, comorbidity and multimorbidity. At the same time, “associative polymorbidity” is distinguished with a certain set of diseases that often occur in conjunction with each other with individual susceptibility of the body. One of the most common phenotypes of polymorbidity occurring in all age groups in both sexes is cardiometabolic, which is based on the formation of insulin resistance, sympathetic overactivity and chronic inflammation. This article provides a clinical example of the use of a fixed combination of angiotensin II receptor blocker telmisartan and calcium channel blocker amlodipine with the addition of an I1-imidazoline receptor agonist moxonidine in real clinical practice in a polymorbid cardiometabolic patient with target organ damage (left ventricular hypertrophy and microalbuminuria). High antihypertensive (favorable effect on 24-hour blood pressure, especially in the early morning) and organoprotective effectiveness of this combination, its possibilities in correcting additional risk factors (reduced heart rate, body weight and a positive effect on metabolic parameters), due to a synergistic effect on the central pathogenetic mechanisms of hypertension and obesity – insulin resistance and sympathetic overactivity.

About the Authors

O. D. Ostroumova
Russian Medical Academy of Continuing Professional Education; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Olga D. Ostroumova


eLibrary SPIN 3910-6585

I. A. Alyautdinova
Russian Medical Academy of Continuing Professional Education
Russian Federation

Irina A. Alyautdinova


eLibrary SPIN 3684-3046

S. N. Litvinova
Russian Medical Academy of Continuing Professional Education
Russian Federation

Svetlana N. Litvinova


eLibrary SPIN 5570-1457

A. V. Arablinskij
Russian Medical Academy of Continuing Professional Education; City Clinical Hospital n.a. S.P. Botkin
Russian Federation

Alexander V. Arablinskij


eLibrary SPIN 5221-4250

A. A. Kirichenko
Russian Medical Academy of Continuing Professional Education
Russian Federation

Andrey A. Kirichenko


eLibrary SPIN 1243-4133


1. Kobalava Zh.D., Konradi A.O., Nedogoda S.V. Arterial hypertension in adults. Clinical guidelines 2020. Russian Journal of Cardiology. 2020;25(3):37-86 (In Russ.) DOI:10.15829/1560-4071-2020-3-3786.

2. DuGoff E.H., Canudas-Romo V., Buttorff C., et al. Multiple chronic conditions and life expectancy: a life table analysis. Med Care. 2014;52(8):688-94. DOI:10.1097/MLR.0000000000000166.

3. Oganov R.G., Simanenkov V.I., Bakulin I.G. Clinical guidelines. Comorbidities in clinical practice. Algorithms for diagnostics and treatment. Cardiovascular Therapy and Prevention 2019;18(1):5-66 (In Russ.) DOI:10.15829/1728-8800-2019-1-5-66.

4. Tarlovskaya E.I. Comorbidity and polymorbidity -a modern interpretation and urgent tasks facing the therapeutic community. Kardiologiia. 2018;58(9S):29-38 (In Russ.) DOI:10.18087/cardio.2562.

5. Prados-Torres A., Calderón-Larrañaga A., Hancco Saavedra J., et al. Multimorbidity patterns: a systema¬tic review. Journal of Clinical Epidemiology 2014;67(3):254-66. DOI:10.1016/j.jclinepi.2013.09.021.

6. Van den Akker M., Buntinx F., Metsemakers J.F.M., et al. Multimorbidity in General Practice: Prevalence, Incidence, and Determinants of Co-Occurring Chronic and Recurrent Diseases. Journal of Clinical Epidemiology 1998;51(5):367-75. DOI:10.1016/S0895-4356(97)00306-5.

7. Vogeli C., Shields A.E., Lee T.A. et al. Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs. Journal of General Internal Medicine 2007;22(S3):391-5. DOI:10.1007/s11606-007-0322-1.

8. Prados-Torres A. Poblador-Plou B., Calderón-Larrañaga A. et al. Multimorbidity Patterns in Primary Care: Interactions among Chronic Diseases Using Factor Analysis. PLoS ONE 2012;7(2):e32190. DOI:10.1371/journal.pone.0032190.

9. Oganov R.G., Drapkina O.M. Polymorbidity: specifics of codevelopment and concomitance of several diseases in one patient. Cardiovascular Therapy and Prevention. 2016;15(4):4-9 (In Russ.) DOI:10.15829/1728-8800-2016-4-4-9.

10. Radchenko A.D. Some aspects of the use of dihydropyridine calcium antagonists in the treatment of arterial hypertension. Part 1. Arterial'naja Gipertenzijaю 2013;5(31):81-98 (In Russ.)

11. Thorp A.A., Schlaich M.P. Relevance of Sympathetic Nervous System Activation in Obesity and Metabolic Syndrome. J Diabetes Resю 2015; 2015:341583. DOI:10.1155/2015/341583.

12. Kochetkov A.I., Ostroumova O.D., Starodubova A.V. Association between Sympathetic Nervous System Activation, Obesity and Insulin Resistance. Rational Pharmacotherapy in Cardiology 2019;15(2):230-43 (In Russ.) DOI:10.20996/1819-6446-201915-2-230-243.

13. Michalik L., Auwerx J., Berger J.P., et al. International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors. Pharmacological Reviews. 2006;58(4):726-41. DOI:10.1124/pr.58.4.5.

14. Wakino S., Ronald E.L., Hsueh W.A. Vascular protective effects by activation of nuclear receptor PPARγ. Journal of Diabetes and Its Complications. 2002;16(1):46-9. DOI:10.1016/s1056-8727(01)00197-0.

15. Hsueh W.A., Law R. The central role of fat and effect of peroxisome proliferator-activated receptorgamma on progression of insulin resistance and cardiovascular disease. Am J Cardiol. 2003;92(4A):3-9. DOI:10.1016/s0002-9149(03)00610-6.

16. Derosa G., Cicero A.F.G., D'angelo A., et al. Telmisartan and Irbesartan Therapy in Type 2 Diabetic Patients Treated with Rosiglitazone: Effects on Insulin-Resistance, Leptin and Tumor Necrosis Factorα. Hypertens Res. 2006;29(11):849-56. DOI:10.1291/hypres.29.849.

17. Pitt B., Byington R.P., Furberg C.D., et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102(13):1503-10. DOI:10.1161/01.cir.102.13.1503.

18. Kario K. Morning surge in blood pressure and cardiovascular risk: evidence and perspectives. Hypertension 2010;56(5):765-73. DOI:10.1161/HYPERTENSIONAHA.110.157149.

19. Stangier J., Su C.A., van Heiningen P.N., et al. Inhibitory effect of telmisartan on the blood pressure response to angiotensin II challenge. J Cardiovasc Pharmacol. 2001;38(5):672-85. DOI:10.1097/00005344-200111000-00004.

20. Sharma A.M., Davidson J.A., Gavin J.R. III, et al. Comparison of the antihypertensive efficacy of telmisartan/hydrochlorothiazide vs valsartan/hydrochlorothiazide in high-risk overweight/obese patients with hypertension and type 2 diabetes. Hypertension. 2005;46:898.

21. Williams B., Lacourcie`re Y., Schumacher H., et al. Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours:a pooled analysis of the PRISMA I and II randomized trials. J Hum Hypertens. 2009;23:610-9. DOI:10.1038/jhh.2009.4.

22. Galzerano D., Tammaro Р., Viscovo L., et al. Three-Dimensional Echocardiographic and Magnetic Resonance Assessment of the Effect of Telmisartan Compared With Carvedilol on Left Ventricular Mass: A Multicenter, Randomized, Longitudinal Study. Am J Hypertens. 2005;18(12 Pt 1):1563-9. DOI:10.1016/j.amjhyper.2005.06.011.

23. Petrovic I., Petrovic D., Vukovicetal N., et al. Ventricular and Vascular Remodelling Effects of the Angiotensin II Receptor Blocker Telmisartan and/or the Angiotensin-Converting Enzyme Inhibitor Ramipril in Hypertensive Patients. J Int Med Res. 2005;33(Suppl 1):39-49. DOI:10.1177/14732300050330S106.

24. Barnett А.Н. Preventing Renal Complications in Diabetic Patients: The Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) Study. Acta Diabetol. 2005;42(Suppl 1):42-9. DOI:10.1007/s00592-005-0180-4.

25. Neldam S., Edwards C., Jones R. TEAMSTA-10 Investigators. Switching patients with uncontrolled hypertension on amlodipine 10 mg to single-pill combinations of telmisartan and amlodipine: results of the TEAMSTA-10 study. Curr Med Res Opin. 2011;27(11):2145-53. DOI:10.1185/03007995.2011.624089.

26. Sharma A., Bagchi A., Kinagi S.B., et al. Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension. Clin Ther. 2007;29(12):2667-76. DOI:10.1016/j.clinthera.2007.12.017.

27. Goyal J., Khan Z.Y., Upadhyaya P., et al. Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension. J Clin Diagn Res. 2014;8(6):8-11. DOI:10.7860/JCDR/2014/9352.4500.

28. Neutel J.M., Mancia G., Black H.R., et al. Single-pill combination of telmisartan/amlodipine in patients with severe hypertension: results from the TEAMSTA severe HTN study. J Clin Hypertens (Greenwich). 2012;14(4):206-15. DOI:10.1111/j.1751-7176.2012.00595.x.

29. Fisher J.P., Paton J.F. The sympathetic nervous system and blood pressure in humans: implications for hypertension. J Hum Hypertens. 2012;26(8):463-75. DOI:10.1038/jhh.2011.66.

30. Chazova I., Schlaich M.P. Improved hypertension control with the imidazoline agonist moxonidine in a multinational metabolic syndrome population: principal results of the MERSY Study. International Journal of Hypertension. 2013;2013:1-9. DOI:10.1155/2013/541689.

31. Chazova I.E., Almazov V.A., Shlyakhto E.V. Moxonidine improves glycemic control in patients with arterial hypertension and excess body weight in comparison with metformin: the ALMAZ study. Clinical Cardiology Reviews. 2007;(9):36-47 (in Russ.)

32. Ostroumova O.D., Kochetkov A.I., Lopuhina M.V., Pavleeva E.E. Hypersympathicotonia in the development of left ventricular myocardial hypertrophy and the possibility of beta-blockers for regression. Russian Cardiology Journal. 2018;(9):77-88 (in Russ.) DOI:10.15829/1560-4071-2018-9-77-88.

33. Özel E., Taştan A., Öztürk A., Özcan Е.Е. Relationship between Sympathetic Overactivity and Left Ventricular Hypertrophy in Resistant Hypertension. Hellenic J Cardiol. 2015;56(6):501-6. DOI:10.1016/j.amjcard.2015.01.072.

34. Schlaich M.P., Kaye D.M., Lambert E., et al. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation. 2003;108(5):560-5. DOI:10.1161/01.CIR.0000081775.72651.B6.

35. Palatini P., Saladini F., Mos L., et al. Obesity is a strong determinant of hypertensive target organ damage in young-to-middle-age patients. Int J Obes (Lond). 2013;37(2):224-9. DOI:10.1038/ijo.2012.32.

36. Sanjuliani A.E., Genelhu de Abreu V., Ueleres Braga J., Francischetti E.A. 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 Basic Cardiol. 2004;7(1-4):19-25.

37. Abellán J., Leal M., Hernández-Menárguez F., et al. Efficacy of moxonidine in the treatment of hypertension in obese, noncontrolled hypertensive patients. Kidney Int. 2005;67(suppl 93):20-4. DOI:10.1111/j.1523-1755.2005.09305.x.

38. 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;18(9):669-75. DOI:10.1038/sj.jhh.1001676.

39. Haenni A., Lithell H. Moxonidine improves insulin sensitivity in insulin-resistant hypertensives. J Hypertens. 1999;17(Suppl 3):29-35.

40. Karlafti E.F., Hatzitolios A.I., Karlaftis A., et al. Effects of Moxonidine on Sympathetic Nervous System Activity: An Update on Metabolism, Cardio, and Other Target-Organ Protection. J Pharm Bioallied Sci. 2013;5(4):253-6. DOI:10.4103/0975-7406.120067.

41. Shal'nova S.A., Deev D.A., Belova O.A., et al.; on behalf of the participants in the ESSE-RF study. Heart rate and its association with major risk factors in the working-age population of men and women. Rational Pharmacotherapy in Cardiology. 2017;13(6):819-26 (In Russ.) DOI:10.20996/1819-2017-13-6-819-826.

42. Gillman M.W., Kannel W.B., Belanger A., D’Agostino RB. Influence of heart rate on mortality among persons with hypertension: the Framingham study. Am Heart J. 1993;125(4):1148-54. DOI:10.1016/0002-8703(93)90128-V.

43. Thomas F., Rudnichi A., Bacri A.M., et al. Cardiovascular mortality in hypertensive men according to presence of associated risk factors. Hypertension. 2001;37(5):1256-61. DOI:10.1161/01.hyp.37.5.1256.

44. Paul L., Hastie C.E., Li W.S., et al. Resting heart rate pattern during follow-up and mortality in hypertensive patients. Hypertension. 2010;55(2):567-74. DOI:10.1161/HYPERTENSIONAHA.109.144808.

For citation:

Ostroumova O.D., Alyautdinova I.A., Litvinova S.N., Arablinskij A.V., Kirichenko A.A. Optimization of Pharmacotherapy Within the Framework of a Patient-oriented Approach in the Treatment of Hypertension in Multimorbidity Patients (Clinical Case and Literature Review). Rational Pharmacotherapy in Cardiology. 2021;17(1):124-132. (In Russ.)

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ISSN 1819-6446 (Print)
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