一项比较 azilsartan medoxomil 和氯沙坦与奥美沙坦和氢氯噻嗪固定剂量复方在 2 期收缩期高血压中疗效的随机滴定至靶目标研究。

A randomized titrate-to-target study comparing fixed-dose combinations of azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide in stage-2 systolic hypertension.

机构信息

Veterans Affairs Medical Center, University of Tennessee Health Science Center, Memphis, Tennessee.

University of Chicago Medicine, Chicago, Illinois.

出版信息

J Hypertens. 2018 Apr;36(4):947-956. doi: 10.1097/HJH.0000000000001647.

BACKGROUND

Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).

OBJECTIVE/METHODS: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8-week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg (≥130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also measured.

RESULTS

Greater reductions in clinic SBP from a baseline of 165 mmHg were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8 weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9 versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus 54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ, respectively.

CONCLUSION

This large, titration-to-target BP study demonstrated AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the maximum approved dose of OLM/HCTZ.

背景

阿齐沙坦酯（AZL-M）是一种血管紧张素 II 受体阻滞剂，已与氯噻酮（CTD）制成固定剂量复方制剂（FDC）。

目的/方法：我们比较了每日一次 AZL-M/CTD 20/12.5mg 滴定至 40/25mg（如果需要）或每日一次 AZL-M/CTD 40/12.5mg 滴定至 80/25mg（如果需要）与奥美沙坦酯（OLM）-氢氯噻嗪（HCTZ）20/12.5mg FDC 的疗效，后者每日一次滴定至 40/25mg（如果需要），用于一项随机、双盲、为期 8 周的研究，共纳入 1085 例诊室收缩压（SBP）为 160-190mmHg 和舒张压（DBP）为 119mmHg 或更低的患者。如果血压至少为 140/90mmHg（如果患有糖尿病或慢性肾病则至少为 130/80mmHg），则在第 4 周进行剂量滴定。主要终点为从基线开始诊室 SBP 的变化；还测量了 24 小时动态血压监测。

结果

与 OLM/HCTZ（-31.5mmHg）相比，AZL-M/CTD 两种剂量（-37.6mmHg 和-38.2mmHg）都观察到诊室 SBP 从基线下降更大（P<0.001），尽管 OLM/HCTZ 组的剂量滴定更高。8 周时，AZL-M/CTD 两种 FDC 均比 OLM/HCTZ 更能降低 24 小时 SBP（-26.4mmHg 和-27.9mmHg 对比-20.7mmHg；均 P<0.001），并且 AZL-M/CTD 两组的目标血压达标比例均高于 OLM/HCTZ 组（69.4%和 68.9%对比 54.7%；均 P<0.001）。AZL-M/CTD 较低和较高剂量以及 OLM/HCTZ 组分别有 6.2%、9.5%和 3.1%的患者因不良事件而停药。