UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial

MacDonald, TM; Williams, B; Webb, DJ; Morant, S; Caulfield, M; Cruickshank, JK; Ford, I; ... British Hypertension Society Programme of Prevention And Treatme; + view all (2017) Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial. Journal of the American Heart Association , 6 (11) , Article e006986. 10.1161/JAHA.117.006986. Green open access

[thumbnail of e006986.full.pdf]
Preview
Text
e006986.full.pdf - Published Version

Download (1MB) | Preview

Abstract

BACKGROUND: Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. METHODS AND RESULTS: We performed a 1-year, double-blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0-16), patients were randomly assigned to initial monotherapy (losartan 50-100 mg or hydrochlorothiazide 12.5-25 mg crossing over at 8 weeks), or initial combination (losartan 50-100 mg plus hydrochlorothiazide 12.5-25 mg). In phase 2 (weeks 17-32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33-52), amlodipine with or without doxazosin could be added to achieve target BP. Hierarchical primary outcomes were the difference from baseline in home systolic BP, averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7-6.0 mm Hg) less over 32 weeks (P<0.001) than after initial combination but caught up at 32 weeks (difference 1.2 mm Hg [range: -0.4 to 2.8 mm Hg], P=0.13). In phase 1, home systolic BP response to each monotherapy differed substantially between renin tertiles, whereas response to combination therapy was uniform and at least 5 mm Hg more than to monotherapy. There were no differences in withdrawals due to adverse events. CONCLUSIONS: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617.

Type: Article
Title: Combination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/JAHA.117.006986
Publisher version: https://doi.org/10.1161/JAHA.117.006986
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Angiotensin II receptor blocker, comparative effectiveness, diuretics, renin, treatment effectiveness
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10038847
Downloads since deposit
112Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item