Comparison of 24-Hour Ambulatory Central Blood Pressure Reduction Efficacy Between Fixed Amlodipine or Up-Titrated Hydrochlorothiazide Plus Losartan: The K-Central Study

Eun Joo Cho, Hae Young Lee, Ki Chul Sung, Sungha Park, Il-Suk Sohn, Chang Gyu Park, Dong-Ju Choi, Jong Won Ha, Young Keun Ahn, Jinho Shin, Soon-Jun Hong, Soon Kil Kim, Wook-Jin Chung, Byung Su Yoo, Taek Jong Hong, Ho Joong Youn, Myeong-Chan Cho, Shung Chull Chae, Young Jo Kim, Chong-Jin Kim, Eun Joo Cho, Hae Young Lee, Ki Chul Sung, Sungha Park, Il-Suk Sohn, Chang Gyu Park, Dong-Ju Choi, Jong Won Ha, Young Keun Ahn, Jinho Shin, Soon-Jun Hong, Soon Kil Kim, Wook-Jin Chung, Byung Su Yoo, Taek Jong Hong, Ho Joong Youn, Myeong-Chan Cho, Shung Chull Chae, Young Jo Kim, Chong-Jin Kim

Abstract

Objective: The main objective of this study was to evaluate non-inferiority of office mean systolic blood pressure (BP) reduction efficacy and superiority of 24-hour ambulatory central BP reduction efficacy between losartan combined with fixed dose amlodipine (L/A group) and dose up-titrated hydrochlorothiazide (L/H group) according to office BP.

Methods: We conducted a prospective, randomized, double-blind multicenter trial in 231 patients with hypertensive (mean age = 59.2 ± 12.2 years). Patients received losartan 50 mg monotherapy for 4 weeks, followed by additional use of amlodipine 5 mg or hydrochlorothiazide 12.5 mg for 20 weeks after randomization. The patients who did not achieve the BP goal after 4 weeks' randomization received an increased dose of 100 mg/5 mg for the L/A group and 100 mg/25 mg for L/H group, respectively. The 24-hour ambulatory central BP was measured at baseline and after 20 weeks' treatment.

Results: Office mean systolic BP reduction of L/A group was not inferior to L/H group after 4 weeks' treatment (-17.6 ± 13.3 vs. -14.4 ± 12.6 mm Hg, P = 0.0863) and was not significantly different after 20 weeks' treatment. (-15.7 ± 14.0 vs. -14.7 ± 15.1 mm Hg, P = 0.6130) The 24-hour ambulatory central systolic BP was significantly more reduced in the L/A group compared with that in the L/H group after 20 weeks' treatment (-9.37 ± 10.67 vs. -6.28 ± 10.50 mm Hg, P = 0.0407). The 24-hour ambulatory central systolic BP at the completion of the study and its reduction magnitude were independently associated with reductions in aortic pulse wave velocity, pulse pressure, and wave reflection magnitude.

Conclusion: Office systolic BP reduction with L/A was not inferior to L/H after 4 week's treatment. The combination of losartan and amlodipine was more favorable in 24-hour ambulatory central hemodynamics beyond BP-lowering efficacy than the combination of losartan and hydrochlorothiazide, regardless of office BP.

Clinical trials registration: NCT02294539.

Keywords: amlodipine; blood pressure; central blood pressure; combination; hydrochlorothiazide; hypertension; losartan.

© The Author(s) 2019. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.

Figures

Figure 1.
Figure 1.
Study design of multicenter, double-blind, active-controlled, randomized trial with two treatment arms. Both losartan 50 mg plus amlodipine 5 mg combination arm and losartan 50 mg plus hydrochlorothiazide 12.5 mg combination arm were dose up-titrated to losartan 100 mg, with the same dose of amlodipine (5 mg) or hydrochlorothiazide 25 mg, respectively, in case of failure to achieve the blood pressure (BP) goal (mean sitting systolic BP ≥ 140 mm Hg) after 4 weeks of combination therapy. At the baseline and study completion, office brachial BP, 24-hour central BP, 24-hour aortic pulse wave velocity, and other 24-hour hemodynamic parameters were measured using the Mobil-O-Graph device. Blood and urine tests were performed at the baseline and end of the study.
Figure 2.
Figure 2.
Bar graph shows changes in office systolic blood pressure (BP) and 24-hour ambulatory central systolic BP in the two groups (a) and 24-hour measured aortic pulse wave velocity (aPWV) (m/s), AI@75 (%), and reflection magnitude of wave (%) in the two groups (b). There are significant differences in reduction of 24-hour central systolic BP between groups (a). Moreover, there are significantly greater reductions in aPWV and wave reflection magnitude in losartan plus amlodipine combination group compared with that in losartan plus hydrochlorothiazide group.

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