Low-dose triple antihypertensive combination therapy in patients with hypertension: A randomized, double-blind, phase ii study

Soon Jun Hong, Ki Chul Sung, Sang Wook Lim, Seokyeon Kim, Weon Kim, Jinho Shin, Sungha Park, Hae Young Kim, Moo Yong Rhee

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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 amlo-dipine 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: ClinicalTrials.gov identifier NCT03897868.

Original languageEnglish
Pages (from-to)5735-5746
Number of pages12
JournalDrug Design, Development and Therapy
Publication statusPublished - 2020

Bibliographical note

Publisher Copyright:
© 2020 Hong et al.


  • Amlodipine
  • Blood pressure
  • Chlorthalidone
  • Combination therapy
  • Hypertension
  • Losartan
  • Low-dose

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery


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