A multicenter, randomized, and double-blind phase IV clinical trial to compare the efficacy and safety of fixed-dose combinations of amlodipine orotate/valsartan 5/160mg versus valsartan/ hydrochlorothiazide 160/12.5mg in patients with essential hypertension uncontrolled by valsartan 160mg monotherapy

Youngkeun Ahn, Yongcheol Kim, Kiyuk Chang, Weon Kim, Moo Yong Rhee, Kwang Soo Cha, Min Su Hyon, Chi Young Shim, Sung Yun Lee, Doo Il Kim, Sang Wook Kim, Sang Wook Lim, Kyoo Rok Han, Sang Ho Jo, Nae Hee Lee, Jun Kwan, Taehoon Ahn

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Background: To determine whether the effectiveness and safety of fixed-dose combinations (FDCs) of amlodipine orotate/ valsartan (AML/VAL) 5/160 mg are noninferior to those of valsartan/hydrochlorothiazide (VAL/HCTZ) 160/12.5 mg in hypertensive patients with inadequate response to valsartan 160 mg monotherapy. Methods: This 8-week, active-controlled, parallel-group, fixed-dose, multicenter, double-blind randomized controlled, and noninferiority trial was conducted at 17 cardiovascular centers in the Republic of Korea. Eligible patients had mean sitting diastolic blood pressure (msDBP) ≥90 mm Hg despite monotherapy with valsartan 160 mg for 4 weeks. Patients were randomly assigned to treatment with AML/VAL 5/160 mg FDC (AML/VAL) group or VAL/HCTZ 160/12.5 mg FDC (VAL/HCTZ) group once daily for 8 weeks. A total of 238 patients were enrolled (AML/VAL group, n = 121; VAL/HCTZ group, n = 117), of whom 228 completed the study. Results: At 8 weeks after randomization, msDBP was significantly decreased in both groups (9.44 ± 0.69 mm Hg in the AML/VAL group and 7.47 ± 0.71 mm Hg in the VAL/HCTZ group, both P < .001 vs baseline). Between group difference was 1.96 ± 1.00 mm Hg, indicating that AML/VAL 5/160 mg FDC was not inferior to VAL/HCTZ 160/12.5 mg FDC at primary efficacy endpoint. Control rate of BP defined as the percentage of patients achieving mean sitting SBP (msSBP) <140 mm Hg or msDBP <90 mm Hg (target BP) from baseline to week 8 was significantly higher in the AML/VAL group than that in the VAL/HCTZ group (84.3% [n = 102] in the AML/VAL group vs 71.3% [n = 82] in the VAL/HCTZ group, P = .016). At 8 weeks after randomization, mean uric acid level was significantly increased in the VAL/HCTZ group compared to that at baseline (0.64 ± 0.08 mg/dL; P < .001). However, it was slightly decreased from baseline in the AML/VAL group (0.12 ± 0.08 mg/dL; P = .085). The intergroup difference was significant (P < .001). Conclusion: The effectiveness and safety AML/VAL 5/160mg FDC are noninferior to those of VAL/HCTZ 160/12.5mg FDC in patients with hypertension inadequately controlled by valsartan 160mg monotherapy.

Original languageEnglish
Article numbere12329
JournalMedicine (United States)
Issue number37
Publication statusPublished - 2018 Sep


All Science Journal Classification (ASJC) codes

  • Medicine(all)

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