Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial
Abstract Background Guidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown. Methods A randomized blinded crossov...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | BMC Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12916-025-03892-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571620476059648 |
|---|---|
| author | Xiexiong Zhao Tao Liu Qiong Yang Guoping Yang Xingli Li Xiaohong Tang Jingle Li Zhongshu Liang Anying Li Lixiong Zeng Juan Wen Xiaoyan Wang Liping Peng Wenjuan Wang Jingjing Cai Ye Chen Miao Huang Ruixuan Li Ru Fu Lin Zhao Xiaogang Li Weihong Jiang |
| author_facet | Xiexiong Zhao Tao Liu Qiong Yang Guoping Yang Xingli Li Xiaohong Tang Jingle Li Zhongshu Liang Anying Li Lixiong Zeng Juan Wen Xiaoyan Wang Liping Peng Wenjuan Wang Jingjing Cai Ye Chen Miao Huang Ruixuan Li Ru Fu Lin Zhao Xiaogang Li Weihong Jiang |
| author_sort | Xiexiong Zhao |
| collection | DOAJ |
| description | Abstract Background Guidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown. Methods A randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg), both in a single pill, in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded. The main outcomes were the reduction of blood pressure and safety outcomes. Analyses were per intention to treat. Results A total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age was 43.88 years (SD 10.31), and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Compared to the standard-dose dual treatment, the half-dose quadruple treatment resulted in a further reduction in mean 24-h blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure), mean daytime blood pressure by 5.52/4.73 mm Hg (P < 0.001 for both), mean nighttime blood pressure by 2.37/2.25 mm Hg (P = 0.034 and 0.014, respectively), and mean office blood pressure by 2.91/1.73 mm Hg (P < 0.001 and 0.014, respectively). Apart from significant increases of fasting blood glucose (P = 0.029) and blood uric acid (P < 0.001) in the half-dose quadruple group, no other adverse events or changes in laboratory values differed significantly between the two treatments. Conclusions Initiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable. Trial registration ClinicalTrials.gov Identifier: NCT05377203. |
| format | Article |
| id | doaj-art-e422bb9f274a4283ad0ad8e1e5f4c968 |
| institution | Kabale University |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj-art-e422bb9f274a4283ad0ad8e1e5f4c9682025-02-02T12:28:14ZengBMCBMC Medicine1741-70152025-01-0123111310.1186/s12916-025-03892-8Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trialXiexiong Zhao0Tao Liu1Qiong Yang2Guoping Yang3Xingli Li4Xiaohong Tang5Jingle Li6Zhongshu Liang7Anying Li8Lixiong Zeng9Juan Wen10Xiaoyan Wang11Liping Peng12Wenjuan Wang13Jingjing Cai14Ye Chen15Miao Huang16Ruixuan Li17Ru Fu18Lin Zhao19Xiaogang Li20Weihong Jiang21Department of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictCenter of Clinical Pharmacology, The Third Xiangya Hospital of Central South UniversityDepartment of Epidemiology, XiangYa School of Public HealthDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictDepartment of Cardiology, The Third Xiangya Hospital of Central South University, Yuelu DistrictAbstract Background Guidelines recognized dual combination in initial antihypertensive therapy. Studies found that low-dose quadruple combination were superior to monotherapy. However, whether low-dose quadruple therapy is better than dual combination is unknown. Methods A randomized blinded crossover trial was conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg), both in a single pill, in the initial treatment of patients with mild to moderate hypertension. Patients were randomly assigned in a 1:1 ratio to two crossover sequences. Each sequence received four-weeks of either half-dose quadruple antihypertensives or standard-dose dual antihypertensives, followed by a two-week washout and crossover for four-weeks. Participants and researchers were blinded. The main outcomes were the reduction of blood pressure and safety outcomes. Analyses were per intention to treat. Results A total of 90 eligible participants were randomized between July 13, 2022, and April 20, 2023. The mean age was 43.88 years (SD 10.31), and 25.6% were women. The mean baseline 24-h blood pressure was 145.59/93.84 mm Hg. Compared to the standard-dose dual treatment, the half-dose quadruple treatment resulted in a further reduction in mean 24-h blood pressure by 4.72/4.17 mm Hg (P < 0.001 for both systolic and diastolic blood pressure), mean daytime blood pressure by 5.52/4.73 mm Hg (P < 0.001 for both), mean nighttime blood pressure by 2.37/2.25 mm Hg (P = 0.034 and 0.014, respectively), and mean office blood pressure by 2.91/1.73 mm Hg (P < 0.001 and 0.014, respectively). Apart from significant increases of fasting blood glucose (P = 0.029) and blood uric acid (P < 0.001) in the half-dose quadruple group, no other adverse events or changes in laboratory values differed significantly between the two treatments. Conclusions Initiating treatment with half-dose quadruple combination therapy was more effective in lowering blood pressure than standard-dose dual therapy. The safety of half-dose quadruple therapy was comparable. Trial registration ClinicalTrials.gov Identifier: NCT05377203.https://doi.org/10.1186/s12916-025-03892-8HypertensionAntihypertensiveLow-dose combinationRandomized controlled trial |
| spellingShingle | Xiexiong Zhao Tao Liu Qiong Yang Guoping Yang Xingli Li Xiaohong Tang Jingle Li Zhongshu Liang Anying Li Lixiong Zeng Juan Wen Xiaoyan Wang Liping Peng Wenjuan Wang Jingjing Cai Ye Chen Miao Huang Ruixuan Li Ru Fu Lin Zhao Xiaogang Li Weihong Jiang Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial BMC Medicine Hypertension Antihypertensive Low-dose combination Randomized controlled trial |
| title | Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial |
| title_full | Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial |
| title_fullStr | Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial |
| title_full_unstemmed | Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial |
| title_short | Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): a randomized, blinded, crossover trial |
| title_sort | initial treatment with a single capsule containing half dose quadruple therapy vs standard dose dual therapy in hypertensive patients quadual a randomized blinded crossover trial |
| topic | Hypertension Antihypertensive Low-dose combination Randomized controlled trial |
| url | https://doi.org/10.1186/s12916-025-03892-8 |
| work_keys_str_mv | AT xiexiongzhao initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT taoliu initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT qiongyang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT guopingyang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT xinglili initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT xiaohongtang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT jingleli initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT zhongshuliang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT anyingli initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT lixiongzeng initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT juanwen initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT xiaoyanwang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT lipingpeng initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT wenjuanwang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT jingjingcai initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT yechen initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT miaohuang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT ruixuanli initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT rufu initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT linzhao initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT xiaogangli initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial AT weihongjiang initialtreatmentwithasinglecapsulecontaininghalfdosequadrupletherapyvsstandarddosedualtherapyinhypertensivepatientsquadualarandomizedblindedcrossovertrial |