Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 6, Issue 11, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.117.006986
Keywords
angiotensin II receptor blocker; comparative effectiveness; diuretics; renin; treatment effectiveness
Categories
Funding
- British Heart Foundation [SP/08/002]
- National Institute of Health Research Comprehensive Local Research Networks
- National Institute of Health Research University College London Hospitals Biomedical Research Centre
- National Institute of Health Research Cardiovascular Biomedical Research Unit at St Bartholomew's Hospital, London
- National Institute of Health Research Research Fellowship
- British Heart Foundation [SP/08/002/24118] Funding Source: researchfish
- Medical Research Council [MR/K006584/1, MC_PC_13090, MC_PC_11004, G0600237] Funding Source: researchfish
- National Institute for Health Research [12/01/52, NF-SI-0512-10113, NF-SI-0611-10273, NF-SI-0514-10011, NF-SI-0513-10059, NF-SI-0509-10222] Funding Source: researchfish
- MRC [G0600237, MC_PC_11004, MC_PC_13090] Funding Source: UKRI
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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.
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