The recent Treatment in Morning versus Evening (TIME) study generated controversy by testing the cardiovascular (CV) benefit of antihypertensives taken in the evening compared to conventional morning dosing.1 Results from the study found no CV benefit to evening dosing and no significant observed difference in CV harms. This suggests that time of administration should not be a significant barrier to adherence when advising patients on the use of antihypertensives.2, 4
The prospective, parallel-group study in the United Kingdom enrolled and randomized >21,000 adults with hypertension who were prescribed at least one antihypertensive to either morning or evening dosing for all their usual medications. Participants were followed for a median of 5.2 years. Primary endpoint CV events (composite of vascular death or hospitalization for non-fatal myocardial infarction or non-fatal stroke) occurred in 362 (3.4%) of patients assigned to evening treatment versus 390 (3.7%) in the morning group. Side effects did not differ significantly between groups.
Study limitations included a decentralized trial structure, with all instructions and adherence checks occurring online. The self-reported ethnicity of participants was >90% White, and >57% were never-smokers, potentially limiting generalizability to broader populations, including those with limited digital literacy.
- Mackenzie IS, Rogers A, Poulter NR, et al. 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. Lancet. 2022;400(10361):1417-1425. doi:10.1016/S0140-6736(22)01786-X.
- Stergiou G, Brunström M, MacDonald T, et al. Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension. J Hypertens. 2022;40(10):1847-1858. doi:10.1097/HJH.0000000000003240.
- Poulter NR, Savopoulos C, Anjum A, et al. Randomized crossover trial of the impact of morning or evening dosing of antihypertensive agents on 24-hour ambulatory blood pressure. Hypertension. 2018;72(4):870-873. doi:10.1161/HYPERTENSIONAHA.118.11101.
- Hermida RC, Mojón A, Smolensky MH, Fernández JR. Lowering nighttime blood pressure with bedtime dosing of antihypertensive medications: controversies in hypertension-pro side of the argument. Hypertension. 2021;78(3):879-893. doi:10.1161/HYPERTENSIONAHA.120.16500.