The timing of antihypertensive medication dosing does not have a significant effect on major cardiovascular outcomes, according to results of a study published in The Lancet.
The TIME (Treatment in Morning Versus Evening) study was a prospective, pragmatic, decentralized, parallel-group study that recruited participants in the United Kingdom between 2014 and 2017. Patients (N=21,104) with hypertension who were taking one or more antihypertensive medications were randomly assigned to either take their medications between 6:00 and 10:00 in the morning (n=10,601) or between 20:00 and 00:00 in the evening (n=10,503). The primary composite endpoint was the time to vascular death, nonfatal myocardial infarction (MI) hospitalization, or nonfatal stroke hospitalization through March 2021.
The morning and evening cohorts comprised patients with a mean age of 65.2 (SD, 9.2) and 65.0 (SD, 9.3) years, 90.8% and 90.2% were White, they had a mean body mass index of 28.4 (SD, 4.9) and 28.4 (SD, 4.8), 12.8% and 13.0% had evidence of cardiovascular disease, 4.4% and 4.9% had a previous MI, and 2.2% and 2.5% had a previous stroke, respectively. In both groups, 57.5% were men.
Prior to randomization, 85.4% reported taking their medication in the morning.
As of the data cutoff, 631 participants had a first primary endpoint event. The rates of the primary composite endpoint were 4.1% for the morning and 4.2% for the evening cohorts. Risk for the primary endpoint did not differ between the 2 groups (hazard ratio [HR], 0.95; 95% CI, 0.83-1.10; P =.53).
No group differences in the rates of hospitalization for nonfatal MI, hospitalization for nonfatal stroke, vascular death, all-cause death, and hospitalization or death from congestive heart failure were observed.
Among the subset of patients who had an at-home blood pressure monitor, the evening dosing group consistently reported lower morning-assessed systolic blood pressure (BP; mean difference [MD], -1.8 mm Hg; P <.0001) and diastolic BP (MD, -0.4 mm Hg; P =.023) but higher evening-assessed systolic BP (MD, 1.1 mm Hg; P <.0001) and diastolic BP (MD, 0.9 mm Hg; P <.0001) compared with the morning dosing group.
The adherence rate to the assigned dosing time was 69.3%. The time to first nonadherence event was 1.7 years and was more common among the evening group than the morning group (39.0% vs 22.5%; P <.0001). A total of 11.6% of the population withdrew from the study early, among whom more were randomly assigned to take their medication at night (62.7%).
In the safety analysis, the evening group associated with fewer falls (21.1% vs 22.2%), upset stomach or indigestion (27.6% vs 30.3%), diarrhea (18.8% vs 21.6%), and muscle ache (38.9% vs 43.3%) events but more excessive visits to the toilet (40.0% vs 36.4%) compared with the morning group, respectively.
The major limitations of this study are the higher withdrawal and nonadherence rates observed among the evening group.
“Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes,” the study authors wrote, “Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Mackenzie IS, Rogers A, Poulter NR, et al; on behalf of the TIME study group. 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. Published online October 11, 2022. doi:10.1016/S0140-6736(22)01786-X