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Low-Dose Triple Antihypertensive Combination Therapy in Patients with Hypertension: A Randomized, Double-Blind, Phase II Study

Authors Hong SJ, Sung KC, Lim SW, Kim SY, Kim W, Shin J, Park S, Kim HY, Rhee MY

Received 18 October 2020

Accepted for publication 21 December 2020

Published 31 December 2020 Volume 2020:14 Pages 5735—5746


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Tin Wui Wong

Soon Jun Hong, 1,* Ki-Chul Sung, 2,* Sang-Wook Lim, 3 Seok-Yeon Kim, 4 Weon Kim, 5 Jinho Shin, 6 Sungha Park, 7 Hae-Young Kim, 8 Moo-Yong Rhee 9, 10 On behalf of MH_APOLLO to read: HM_APOLLO

1Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 2Department of Cardiology, Gangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea; 3Cardiology Division, Cardiac Center, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 4Department of Cardiology, Seoul Medical Center, Seoul, Republic of Korea; 5Department of Internal Medicine, Kyung Hee University Medical Center, Kyung Hee University, Seoul, Republic of Korea; 6Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 7Department of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Health Care Science, Graduate School, Korea University, Seoul, Republic of Korea; 9Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang-si, Gyeonggi, Republic of Korea; 10College of Medicine, Dongguk University, Gyeongju-si, Gyeongbuk, Republic of Korea

*These authors contributed equally to this work

Correspondence: Moo-Yong Rhee
Cardiovascular Center, Dongguk University Ilsan Hospital, 27 Dongguk-Ro, Ilsandong-Gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea
Tel +82 31 961 5775
Fax +82 31 961 7786
Email [email protected]

Purpose: We evaluated the dose-responsiveness, efficacy, and safety of low-dose triple antihypertensive combination therapies in patients with mild-to-moderate hypertension.
Patients and Methods: After a 1 to 2-week placebo run-in period, 248 patients were randomized to the half-dose triple combination (amlodipine 2.5 mg + losartan 25 mg + chlorthalidone 6.25 mg), third-dose triple combination (amlodipine 1.67 mg + losartan 16.67 mg + chlorthalidone 4.17 mg), quarter-dose triple combination (amlodipine 1.25 mg + losartan 12.5 mg + chlorthalidone 3.13mg), amlodipine 10mg, amlodipine 5mg, losartan 100mg, and placebo groups for 8 weeks. The primary outcome was the mean change in systolic blood pressure (SBP) from baseline to week 8.
Results: The placebo-corrected SBP reductions of the half-dose, third-dose, quarter-dose combination, amlodipine 10 mg, amlodipine 5 mg and losartan 100 mg treatments were − 17.2, − 19.5, − 14.9, − 18.5, − 11.3 and − 9.9 mmHg, respectively. The BP control and response rates were significantly higher in the half-dose, third-dose, and quarter-dose combination groups than in the placebo group (all p < 0.01). Despite no intergroup differences in study drug-related adverse events, ankle circumference increased significantly in the amlodipine group compared to those in the combination treatment groups. The quarter-dose combination, amlodipine 5 mg, and losartan 100 mg groups showed similar SBP reduction and BP response rates. The SBP reduction and BP response rate in the third-dose and half-dose combination groups were not significantly different from those in the amlodipine 10 mg group but superior to those in the losartan 100 mg group.
Conclusion: Low-dose triple combination therapies could be effective as antihypertensive therapies.
Trial Registration: identifier NCT03897868.

Keywords: hypertension, blood pressure, combination therapy, low-dose, amlodipine, losartan, chlorthalidone

Corrigendum for this paper has been published

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