TIME
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
58.0% male
N = 21104
21104 patients (8968 female, 12136 male).
Inclusion criteria: adult patients 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).
Primary outcome
Vascular death or hospitalization for nonfatal MI or nonfatal stroke
3.4%
3.7%
3.7 %
2.8 %
1.9 %
0.9 %
0.0 %
Evening
dosing
Morning
dosing
No significant
difference ↔
No significant difference in vascular death or hospitalization for nonfatal MI 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 MI (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 all-cause mortality (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 adult patients with hypertension and taking ≥ 1 antihypertensive medication, evening dosing was not superior to morning dosing with respect to vascular death or hospitalization for nonfatal MI 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.
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