NEW ANGIOTENSIN II RECEPTOR BLOCKER FIMASARTAN IN MILD-TO-MODERATE HYPERTENSION: POST-HOC ANALYSIS OF RESULTS OF REGISTRATION TRIAL IN RUSSIA

Objective. We performed post-hoc analysis of results of multicenter open-label randomized comparative trial on antihypertensive efficacy and safety of fimasartan and losartan in parallel groups for adult outpatients with mildto-moderate hypertension (HTN) during 12 weeks of treatment in order to determine characteristics associated with better treatment efficacy. Design and methods. Post hoc analysis included ITT (intention-to-treat) population: 89 patients from fimasartan group and 90 patients from losartan group. We assessed associations between change from baseline in “office” sitting systolic and diastolic blood pressure and gender, age, anthropometric parameters, duration and severity of hypertension, previous antihypertensive treatment, clinical and laboratory parameters on study visits, and doses of studied drugs. Statistical package R (version 3.0.2, The R Foundation for Statistical Computing 2013) was used for analysis. Results. Fimasartan and losartan provided comparable blood pressure lowering effect in gender, age subgroups, in patients with different duration and severity of hypertension, risk factors profiles. There was a trend toward higher blood pressure decrease in patients with body mass index (BMI) ≥ 30 kg/m 2 in fimasartan group. In the overall population BMI ≥ 30 kg/m 2 was associated with 2-fold increase of risk of dose change at any visit: odds ratio (OR) = 2,1 (95 % confidential interval (CI): 1,08–3,91). However, study groups analysis demonstrated that it was true only for losartan: OR = 2,75 (95 % CI: 1,1–6,88; р = 0,036). Fimasartan was equally effective in both obese and normal weight patients: OR = 1,50 (95 % CI: 0,63–3,93; р = 0,356). Conclusions. Hypertensive patients with BMI ≥ 30 kg/m 2 may benefit more from fimasartan treatment. This fact needs confirmation in further studies with larger sample size.

arterial hypertension, angiotensin II receptors antagonist, fimasartan, obesity, post hoc analysis

1. Qvarnstrom M, Kahan T, Kieler H, Brandt L, Hasselstrom Y, Bostrom K et al. Persistence to antihypertensive drug treatment in Swedish primary healthcare. Eur J Clin Pharmacol. 2013;69(11): 1955–64. doi:10.1097/MD.0000000000004908

2. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M et al. Task Force Members. 2013 ESH/ESC 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. 2013;31(7):1281–1357. doi:10.1097/01.hjh.0000431740.32696.cc

3. Paz MA, de-La-Sierra A, Sáez M, Barceló MA, Rodríguez JJ, Castro S et al. Treatment efficacy of anti-hypertensive drugs in monotherapy or combination. ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement. Medicine. 2016;95(30): e4071. doi:10.1097/MD.0000000000004071

4. Baguet JP, Robitail S, Boyer L, Debensason D, Auquier P. A meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure. Am J Cardiovasc Drugs. 2005;5 (2):131–40.

5. Baguet JP, Legallicier B, Auquier P, Robitail S. Updated meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure. Clin Drug Investig. 2007;27 (11):735–53.

6. Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess. 2003;7(31):49–58.

7. Fabia MJ, Abdilla N, Oltra R, Fernandez C, Redon J. Antihypertensive activity of angiotensin II AT1 receptor antagonists: a systematic review of studies with 24h ambulatory blood pressure monitoring. J Hypertens. 2007;25(7):1327–36.

8. Smith DH. Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. Drugs. 2008;68(9):1207–25.

9. De´zsi CA. The different therapeutic choices with ARBs. Which one to give? When? Why? Am J Cardiovasc Drugs. 2016;16 (4):255–266. doi:10.1007/s40256-016-0165-4

10. Звартау Н. Э., Конради А. О., Корнева Е. В., Бессонова Н. А., Болдуева С. А., Егорова Л. П и др. Сравнение антигипертензивной эффективности и безопасности нового представителя класса антагонистов рецепторов к ангиотензину II — фимасартана и лозартана при артериальной гипертензии 1–2-й степени. Артериальная гипертензия. 2016;22 (2):204–216. doi: http://dx.doi.org/10.18705/1607-419X-2016-22-2-204-216 [Zvartau NE, Konradi AO, Korneva EV, Bessonova NA, Boldueva SA, Egorova LP et al. Efficacy and safety of fimasartan, a new angiotensin-receptor blocker, compared to losartan in mild-to-moderate hypertension, Arterial’naya Gipertenziya = Arterial Hypertension. 2016;22(2):204–216. doi: http://dx.doi.org/10.18705/1607-419X-2016-22-2-204-216. In Russian].

11. Keyhani S, Scobie JV, Hebert PL, McLaughlin MA. Gender disparities in blood pressure control and cardiovascular care in a national sample of ambulatory care visits. Hypertension. 2008;51 (4): 1149–55. doi:10.1161/HYPERTENSIONAHA.107.107342

12. Gu Q, Burt VL, Paulose-Ram R, Dillon CF. Gender differences in hypertension treatment, drug utilization patterns, and blood pressure control among US adults with hypertension: data from the National Health and Nutrition Examination Survey1999–2004. Am J Hypertens. 2008;21(7):789–98. doi: 10.1038/ajh.2008

13. Journath G, Hellenius ML, Petersson U, Theobald H, Nilsson PM, Hyper QSGS. Sex differences in risk factor control of treated hypertensives: a national primary healthcare-based study in Sweden. Eur J Cardiovasc Prevent Rehabil. 2008;5(3):258–62. doi:https://doi.org/10.1097/HJR.0b013e3282f37a45

14. Ljungman C, Kahan T, Schiöler L, Hjerpe P, Hasselström J, Wettermark B et al. Gender differences in antihypertensive drug treatment: results from the Swedish Primary Care Cardiovascular Database (SPCCD). J Am Soc Hypertens. 2014;8(12):882–90. doi:10.1016/j.jash.2014.08.015

15. Kim S, Joo S, Shin M, Kim C, Cho E, Sung K et al. Clinic and home blood pressure lowering effect of an angiotensin receptor blocker, fimasartan, in postmenopausal women with hypertension. Medicine. 2016;95(22): e3764. doi:10.1097/MD.0000000000003764

16. Lima R, Wofford M, Reckelhoff JF. Hypertension in postmenopausal women. Curr Hypertens Rep. 2012;14(3):254–260. doi:10.1007/s11906-012-0260-0

17. Yanes LL, Romero DG, Iliescu R, Zhang H, Davis D, Reckelhoff J. Postmenopausal hypertension: role of the reninangiotensin system. Hypertension. 2010;56(3):359–363. doi:10.1161/HYPERTENSIONAHA.110.152975

18. Shin M, Kang D, Kim C, Cho E, Sung K, Kanget S et al. Fimasartan for independent reduction of blood pressure variability in mild-to-moderate hypertension. Drug Design, Develop Ther. 2016;10:1573–1580. doi:10.2147/DDDT.S107433

19. Kato T, Kikuya M, Ohkubo T, Satoh M, Hara A, Obara T et al. Factors associated with day-by-day variability of self-measured blood pressure at home: the Ohasama study. Am J Hypertens. 2010;23(9):980–986. doi:https://doi.org/10.1038/ajh.2010.94

20. Mallion J, Siche J, Lacourciere Y. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild to moderate hypertension. J Hum Hypertens. 1999;13(10):657–664.

21. de la Sierra A, Banegas JR, Oliveras A, Gorostidi M, Segura J, de la Cruz JJ et al. Clinical differences between resistant hypertensive patients and patients treated and controlled with three or less drugs. J Hypertens. 2012;30(6):1211–6. doi:10.1097/HJH.0b013e328353634e

22. Ивашкин В. Т., Драпкина О. М., Маев В. С., Трухманов С., Блинов Д. В., Пальгова Л. К. и др. Распространенность неалкогольной жировой болезни печени у пациентов амбулаторно-поликлинической практики в Российской Федерации: результаты исследования DIREG 2. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2015;25 (56):31–38. [Ivashkin VT, Drapkina OM, Maev VS, Truhmanov S, Blinov DV, Palgova LK et al. Prevalence of non-alcoholic fatty liver disease in out-patient setting in Russia: results of DIREG 2 study. Rossiyiskyi Zhurnal Gastroenterologii, Hepatologii, Coloproctologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2015;25(56):31–38. In Russian].

23. Драпкина О. М., Елиашевич С. О., Шепель Р. Н. Ожирение как фактор риска хронических неинфекционных заболеваний. Российский кардиологический журнал. 2016; (6):73–79. doi:10.15829/1560-4071-2016-6-73-79 [Drapkina OM, Eliashevich SO, Shepel RN. Obesity as a risk factor for chronic noninfectious diseases. Russian Journal of Cardiology. 2016;(6):73–79. doi:10.15829/1560-4071-2016-6-73-79. In Russian].

24. Lee Y, Jang Y, Han Y et al. Fimasartan ameliorates nonalcoholic fatty liver disease through PPAR and regulation in hyperlipidemic and hypertensive conditions. PPAR Res. 2017: Article ID 8048720: http://dx.doi.org/10.1155/2017/8048720.