Efficacy and safety of azilsartan medoxomil, an angiotensin receptor blocker, in Korean patients with essential hypertension

Abstract

Background: This was a phase 3, randomized, double-blind, placebo-controlled study.

Methods: Adult Korean patients with essential hypertension and a baseline mean sitting clinic systolic blood pressure (scSBP) ≥150 and ≤180 mmHg were randomized to 6-week treatment with placebo (n = 65), azilsartan medoxomil (AZL-M) 40 mg (n = 132), or AZL-M 80 mg (n = 131). The primary endpoint was the change from baseline to week 6 in trough scSBP.

Results: The least-squares mean (standard error) change from baseline in trough scSBP in the placebo, AZL-M 40-mg, and 80-mg groups at week 6 were - 8.8 (2.00), - 22.1 (1.41), and - 23.7 (1.40) mmHg, respectively (p < 0.001 for AZL-M 40 and 80 mg vs placebo). No clinically meaningful heterogeneity in efficacy was observed between subgroups (age, sex, diabetes status) and the overall population. Treatments were well tolerated and adverse events were similar between groups.

Conclusions: Results of this study confirm a positive benefit-risk profile of AZL-M for essential hypertension in Korean adults.

Trial registration: Clinicaltrial.gov; identifier number: NCT02203916. Registered July 28, 2014 (retrospectively registered).

Keywords: Angiotensin II receptor antagonist; Azilsartan medoxomil; Blood pressure; Hypertension; Korea.

Conflict of interest statement

The Institutional Review Boards at each of the 30 study sites were responsible for approval of the clinical study conduct in accordance with ethical principles and the Guidelines of the Declaration of Helsinki, the regulations and guidelines of the International Conference on Harmonisation, Harmonised Tripartite Guideline for Good Clinical Practice, and all applicable local regulations (Additional file 3: Table S2). All patients provided written informed consent prior to screening.Not applicable.AJ was an employee of Takeda Development Centre Europe, Ltd. during the time when the study was conducted. JW and MH are employees of Takeda Development Center Americas, Inc. TT is an employee of Takeda Pharmaceutical Company Ltd., and was an employee of Takeda Development Center Asia, Pte. Ltd. during the time when the study was conducted. MHJ is a TAK-491-307 investigator and Professor of Chonnam National University Hospital, Director of Heart Research Center Nominated by Korea, Ministry of Health and Welfare, Principal Investigator of Korea Acute Myocardial Infarction Registry, and Director of Korea Cardiovascular Stent Research Institute.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Study design. *Patients taking previous antihypertensive agents were required to participate in a 3-week washout (days − 21 to − 1). †If the patient’s previous antihypertensive treatment included amlodipine or chlorthalidone, then the washout was extended to 4 weeks (days − 28 to − 1). ‡Patients who had not received antihypertensive treatment within 28 days prior to screening entered the run-in period as soon as all inclusion and exclusion criteria, including laboratory results, were verified. AZL-M, azilsartan medoxomil; ET, early termination; N/A, not applicable; QD, once daily

Fig. 2

Patient disposition. Patients could have had more than one reason for discontinuation; only the primary reason is presented. AE, adverse event; AZL-M, azilsartan medoxomil

Fig. 3

Least squares mean change from baseline to week 6 in trough sitting clinic systolic blood pressure and sitting clinic diastolic blood pressure. aThe LS mean difference in change from baseline (95% CI) in AZL-M 40 mg versus placebo (mm Hg [95% CI]). bThe LS mean difference in change from baseline (95% CI) in AZL-M 80 mg versus placebo (mm Hg [95% CI]). ***p < 0.001 compared with placebo. Overall treatment effect is statistically significant at 0.05 at all visits for both trough scSBP and scDBP. AZL-M, azilsartan medoxomil; CI, confidence interval; LS, least squares; scDBP, sitting clinic diastolic blood pressure; scSBP, sitting clinic systolic blood pressure

Fig. 4

Proportion of patients who achieved sitting clinic systolic blood pressure and/or sitting clinic diastolic blood pressure response at week 6. AZL-M, azilsartan medoxomil; CI, confidence interval; scDBP, sitting clinic diastolic blood pressure; scSBP, sitting clinic systolic blood pressure; SE, standard error

Fig. 5

Least squares mean change from baseline to week 6 in trough sitting clinic systolic blood pressure and sitting clinic diastolic blood pressure by (a) age, (b) sex, and (c) diabetes status. *p < 0.05 compared with placebo; **p < 0.01 compared with placebo; ***p < 0.001 compared with placebo. AZL-M, azilsartan medoxomil; LS, least squares; scDBP, sitting clinic diastolic blood pressure; scSBP, sitting clinic systolic blood pressure