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dc.contributor.authorMacDonald, TMen_US
dc.contributor.authorWilliams, Ben_US
dc.contributor.authorWebb, DJen_US
dc.contributor.authorMorant, Sen_US
dc.contributor.authorCaulfield, Men_US
dc.contributor.authorCruickshank, JKen_US
dc.contributor.authorFord, Ien_US
dc.contributor.authorSever, Pen_US
dc.contributor.authorMackenzie, ISen_US
dc.contributor.authorPadmanabhan, Sen_US
dc.contributor.authorMcCann, GPen_US
dc.contributor.authorSalsbury, Jen_US
dc.contributor.authorMcInnes, Gen_US
dc.contributor.authorBrown, MJen_US
dc.contributor.authorBritish Hypertension Society Programme of Prevention And Treatment of Hypertension With Algorithm‐based Therapy (PATHWAY)en_US
dc.date.accessioned2018-03-13T13:45:33Z
dc.date.available2017-09-19en_US
dc.date.issued2017-11-18en_US
dc.date.submitted2018-03-13T13:38:07.175Z
dc.identifier.other10.1161/JAHA.117.006986
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/34993
dc.description.abstractBACKGROUND: 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.en_US
dc.description.sponsorshipThe study was funded by a special project grant from the British Heart Foundation (number SP/08/002). Further funding was provided by National Institute of Health Research Comprehensive Local Research Networks. Williams, Sever, Caulfield and Brown are National Institute of Health Research Senior Investigators. Williams is supported by the National Institute of Health Research University College London Hospitals Biomedical Research Centre. Caulfield is supported by the National Institute of Health Research Cardiovascular Biomedical Research Unit at St Bartholomew’s Hospital, London. McCann is supported by National Institute of Health Research Research Fellowshipen_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofJ Am Heart Assocen_US
dc.rightsCreative Commons Attribution License
dc.subjectangiotensin II receptor blockeren_US
dc.subjectcomparative effectivenessen_US
dc.subjectdiureticsen_US
dc.subjectreninen_US
dc.subjecttreatment effectivenessen_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAmlodipineen_US
dc.subjectAntihypertensive Agentsen_US
dc.subjectBlood Pressureen_US
dc.subjectDose-Response Relationship, Drugen_US
dc.subjectDouble-Blind Methoden_US
dc.subjectDoxazosinen_US
dc.subjectDrug Therapy, Combinationen_US
dc.subjectFemaleen_US
dc.subjectFollow-Up Studiesen_US
dc.subjectHumansen_US
dc.subjectHydrochlorothiazideen_US
dc.subjectHypertensionen_US
dc.subjectLosartanen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectTreatment Outcomeen_US
dc.subjectYoung Adulten_US
dc.titleCombination Therapy Is Superior to Sequential Monotherapy for the Initial Treatment of Hypertension: A Double-Blind Randomized Controlled Trial.en_US
dc.typeArticle
dc.rights.holder2017 The Authors.
dc.identifier.doi10.1161/JAHA.117.006986en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/29151036en_US
pubs.issue11en_US
pubs.notesNo embargoen_US
pubs.publication-statusPublished onlineen_US
pubs.volume6en_US
qmul.funderNIHR Barts Cardiovascular Biomedical Research Unit::NIHR Central Commissioning Facilityen_US


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