Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the uk. the time study.

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension. Methods: The TIME study is a prospective, pragmatic, decentralised, parallel group study in the UK, that recruited adults with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned 1 to 1, without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning, 0600 to 1000 h, or in the evening, 2000 to 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 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 i.e. all participants randomly assigned to a treatment group. Findings: Between Dec 17, 2011, and June 5, 2018, 24610 individuals were screened and 21104 were randomly assigned 10503 to evening and 10601 to morning dosing groups. Mean age at study entry was 65·1 years, SD 9·3, 12136 or 57·5 percent participants were men; 8968, 90·5 percent were White, and 2725 or 13·0 percent had a previous cardiovascular disease. By the end of study follow up on March 31, 2021, median follow up was 5·2 years, IQR 4·9, 5·7, 529 of 10503 participants assigned to evening treatment and 318 of 10601 assigned to morning treatment had withdrawn from all follow up. A primary endpoint event occurred in 362 participants assigned to evening treatment that is 0·69 events per 100 patient years and 390 assigned to morning treatment that is 0·72 events per 100 patient years, unadjusted hazard ratio 0·95, 95percent CI 0·83 to 1·10, p 0·53. No safety concerns were identified. An analysis of outcome by adherence to dosing time will be presented at the meeting. Interpretation Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects. Funding British Heart Foundation and the British and Irish Hypertension Society.