Efficacy and safety of fimasartan, a new angiotensin-receptor blocker, compared to losartan in mild-to-moderate hypertension

Background. A phase III multicenter open-label randomized comparative trial on antihypertensive efficacy and safety of fimasartan and losartan in parallel groups for adult outpatients with arterial hypertension (AH) 1–2 grade during 12 weeks of therapy was performed in 13 investigational sites of Russia.

Design and methods. The study included patients with mean systolic blood pressure (SBP) in the sitting position ≥ 140 mm Hg and ≤ 179 mm Hg, previously treated patients underwent a «wash-out» period. The starting therapy was fimasartan 60 mg per day or losartan 50 mg per day, in case blood pressure was maintained at the level SBP ≥ 140 mm Hg and/or diastolic blood pressure (DBP) ≥ 90 mm Hg at 4 and 8 weeks of therapy the doses were increased up
to 100 and 120 mg, respectively. Primary end-point was change from baseline in “office” sitting SBP at week 12 that was intended to show a “non-inferior” fimasartan efficiency (non-significant difference was set at 5,5 mm Hg).

Results. Altogether 179 patients were randomized either to fimasartan (n = 89) or losartan (n = 90) groups. There were no differences between groups by demographic data and the characteristics of hypertension. After 12 weeks of treatment, mean SBP was 127,7 ± 8,0 mm Hg (–25,2 ± 8,6 mm Hg compared with baseline) in group fimasartan and 127,6 ± 5,6 mm Hg (–24,3 ± 7,8 mm Hg compared with baseline) in losartan group. The mean change in SBP was –0,18 ± 1,00 mm Hg (p = 0,390), the upper limit of the 95 % confidence interval was equal to 1,47 mm Hg that confirms the primary criterion of effectiveness. “Non-inferior” fimasartan efficiency was confirmed by the secondary criteria — the change in SBP and DBP at follow-up visits and the response rate. Safety profiles of fimasartan and losartan were comparable.

Conclusions. Fimasartan is well tolerated, safe and provides similar to losartan BP lowering effect in outpatient population.

1. Mancia G, Fagard R, Narkiewicz K, Redón 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.

2. Go AS, Bauman MA, King SM, Fonarow GC, Lawrence W, Williams KA. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension. 2014;63(4):878–885.

3. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L et al. Outcomesin hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363(9426):2022–2031.

4. KDIGO Clinical Practice Guideline for the management of blood pressure in chronic kidney disease. Kidney international supplements.2012;2:337–414.

5. Li J, Culman J, Hortnagi H, Zhao Y, Gerova N, Timm M et al. Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury. FASEB J. 2005;19(6):617–619.

6. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U et al. Cardiovascular morbidity and mortality in patients with diabetesin the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359 (9311):1004–1010.

7. Elliott WJ, Plauschinat CA, Skrepnek GH, Gause D. Persistence, adherence, and risk of discontinuation associated with commonly prescribed antihypertensive drug mono-therapies. J Am Board Fam Med. 2007;20 (1):72–80.

8. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ et al. Investigators. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34(3):552–568.

9. Lee H, Kim KS, Chae SC, Jeong MH, Kim DS, Oh BH. Ambulatory blood pressure response to once-daily fimasartan: an 8‑week, multicenter, randomized, doubleblind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hypertension. Clin Ther. 2013;35(9):1337–1349.

10. Kobalava Z, Korneva E, TolkachevaV, KotovskayaY, Samsonov M, Ajmi H et al. Pharmacokinetic parameters of fimasartan in Russian patients with arterial hypertensions. Journal of Hypertension. 2015;33.e-Suppl 1: e259-e260 (abstract PP.LB01.25).

11. Leonova EV, Belousov DYu, Shteinberg LL, Galitskyi AA, Belousov YuB, analytical group of PIFAGOR study. Results of pharmacoepidemiological hypertension study PIFAGORIII (questioning of hypertensive patients). Systemnye Gipertenzii = Systemic Hypertension. 2010;2:33–39.

12. Asmar R, Safar M, Queneau P. Evaluation of the placebo effect and reproducibility of blood pressure measurement in hypertension. Am J Hypertens. 2001;14 (6 Pt 1):546–552.

13. Julious SA. Sample Sizes for Clinical Trials. In: CRC Press/Taylor & Francis, 2010. p. 330.

14. Park JB, Sung KC, Kang SM, Cho EJ. Safety and efficacy of fimasartan in patients with arterial hypertension (Safe-KanArb study): an open-label observational study. Am J Cardiovasc Drugs. 2013;13(1):47–56. doi: 10.1007/s40256–013–0004–9.

15. Andrade RJ, Lucena MI, Santalla F. Hepatic injury associated with losartan. Ann Pharmacother. 1998;32 (12):1371.

16. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Saf. 1999;21(1):23–33.

17. Rhee M-Y, Baek SH, Kim W, Park CG, Park SW, Oh B‑H et al. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patientsinadequately controlled by fimasartan monotherapy. Drug Design, Development and Therapy. 2015;9:2847–2854.