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

Authors :
MacDonald TM
Williams B
Webb DJ
Morant S
Caulfield M
Cruickshank JK
Ford I
Sever P
Mackenzie IS
Padmanabhan S
McCann GP
Salsbury J
McInnes G
Brown MJ
Source :
Journal of the American Heart Association [J Am Heart Assoc] 2017 Nov 18; Vol. 6 (11). Date of Electronic Publication: 2017 Nov 18.
Publication Year :
2017

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.<br />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.<br />Conclusions: Initial combination therapy can be recommended for patients with BP >150/95 mm Hg.<br />Clinical Trial Registration: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00994617.<br /> (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Details

Language :
English
ISSN :
2047-9980
Volume :
6
Issue :
11
Database :
MEDLINE
Journal :
Journal of the American Heart Association
Publication Type :
Academic Journal
Accession number :
29151036
Full Text :
https://doi.org/10.1161/JAHA.117.006986