Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial.

"Declaration of interests ISM reports research grants from Menarini, EMA, Sanofi, HDR UK, National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA), and Innovative Medicines Initiative outside of the submitted work; institutional consultancy income from AstraZeneca outside of the submitted work; and personal income from AstraZeneca and Amgen outside of the submitted work. TMM reports grants from Menarini/Ipsen/Teijin, NIHR HTA, and MSD outside of the submitted work; personal income for consultancy from Novartis and AstraZeneca outside of the submitted work; and is a trustee of the Scottish Heart Arterial Risk Prevention (SHARP) Society. NRP reports receiving financial support from several pharmaceutical companies that manufacture blood pressure lowering agents for consulting (Servier and Aktiia), research projects and staffing (Servier and Pfizer), and for arranging and speaking at educational meetings (Servier, Sanofi, Eva Pharma, Pfizer, Emcure India, and Dr Reddy's Laboratories); he holds no stocks or shares in any of these companies. BW is supported by the NIHR University College London Hospitals Biomedical Research Centre; reports research grants from Omron, MRC, and NIHR; and reports honoraria from Daiichi Sankyo, Omron, Servier, Pfizer, Novartis, and Menarini outside of the submitted work. MJB is supported by the NIHR Barts Health Biomedical Research Centre and reports research grants from the British Heart Foundation, MRC, and NIHR. PMR declares consultancy income from Abbot and Bayer, and honoraria from Sanofi; he is also a member of the AXIOMATIC trial Data Monitoring Committee. CCL reports membership of a data safety monitoring board or steering committee for Novo Nordisk. AR reports an unpaid membership of an NIHR steering committee. AM reports a British Heart Foundation grant to his university to support salary costs. All other authors declare no competing interests."

"AcknowledgmentsThis study was funded by the British Heart Foundation (CS/14/1/30659) with support from the British and Irish Hypertension Society. ISM, TMM, AR, AM, DAR, GG, and RY received salary through grant funding to their institutions from the British Heart Foundation for this work. Recruitment to this study was facilitated by SHARE – the Scottish Health Research Register and Biobank. SHARE is supported by NHS Research Scotland, Universities in Scotland, and the Chief Scientist Office. The study was also supported by the Scottish Primary Care Research Network, the NIHR Local Clinical Research Networks, and UK Biobank. Additionally, this study received linked data from Public Health Scotland, NHS Digital, SAIL Databank, and HSC Northern Ireland. Responsibility for the interpretation of the information supplied is the authors' alone."

"The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641). Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600–1000 h) or in the evening (2000–0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete."