6/30/23, 2:17 AM TIME Pathway Feedback Search Clinical Topics Home Studies TIME TIME Disease Hypertension Trial question Is evening dosing of antihypertensive therapy superior to morning dosing in patients with hypertension treated with their usual antihypertensive medications? Study design Multi-center Open label RCT Population Characteristics of study participants 42.0% female N = 21104 58.0% male 21104 patients (8968 female, 12136 male) Inclusion criteria: adults with hypertension and taking 1 antihypertensive medication Key exclusion criteria: regular overnight shift work; use of antihypertensive medications at > 1 dosing time daily Interventions N=10503 evening dosing (administration of antihypertensive medications between 20:00 and 00:00) N=10601 morning dosing (administration of antihypertensive medications between 06:00 and 10:00) https://web.pathway.md/studies/recuRPIW8A3S55hte 1/2 6/30/23, 2:17 AM TIME Pathway Primary outcome Vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke 3.7 % 3.7 3.4 2.8 % 1.9 % 0.9 % No significant difference 0.0 % Evening dosing Morning dosing No significant difference in vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke (3.4% vs. 3.7%; HR 0.95, 95% CI 0.83 to 1.1) Secondary outcomes No significant difference in hospitalization for nonfatal myocardial infarction (1.3% vs. 1.4%; HR 0.92, 95% CI 0.73 to 1.16) No significant difference in hospitalization for nonfatal stroke (1.2% vs. 1.3%; HR 0.93, 95% CI 0.73 to 1.18) No significant difference in death from all causes (4.2% vs. 4.1%; HR 1.04, 95% CI 0.91 to 1.18) Safety outcomes No significant differences in fractures, glaucoma. Significant differences in falls (21.1% vs. 22.2%, 1 prespecified symptom adverse events (69.2% vs. 70.5%). Conclusion In adults with hypertension and taking 1 antihypertensive medication, evening dosing was not superior to morning dosing with respect to vascular death or hospitalization for nonfatal myocardial infarction or nonfatal stroke. Reference Isla S Mackenzie, Amy Rogers, Neil R Poulter 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 Oct 22;400(10361):1417-1425. Open reference URL https://web.pathway.md/studies/recuRPIW8A3S55hte 2/2