Cardiovascular Outcomes of Evening vs Morning Dosing of Antihypertensives
The Lancet: Published on October, 2022
Hypertension, or high blood
pressure, is a key risk factor for cardiovascular disease worldwide.
Previous clinical trials supporting
the cardiovascular benefits of antihypertensive therapy primarily use
conventional morning dosing.
Additionally, cardiovascular events
are temporally associated with the morning blood pressure surge.
Evening dosing of antihypertensive
medication has been suggested to potentially be more effective at normalising
the diurnal rhythm, lowering 24 h blood pressure, and preventing the long-term
cardiovascular sequelae of hypertension than morning dosing.
Nocturnal hypertension is an
important predictor of adverse outcomes in people with hypertension, which has
led to the hypothesis that taking antihypertensive medication in the evening
might improve cardiovascular outcomes. So,
· When is the
best time to take blood pressure (BP) medications?
· Is it
during the day when the stress levels are high so we need the medications to
keep the pressure within the normal range?
· Also, would
night dosing be better at suppressing the morning BP surge, which could lead to
plaque rupture and cardiovascular (CV) events?
TAKE-HOME MESSAGE
The present study was sufficiently
well powered to show a clinically important cardiovascular benefit with evening
dosing compared with morning dosing.
Among the 21,104 included patients
in the UK (90.5% White; 42.5% women) with a mean age of 65.1 years, there was
no difference in the incidence of the primary composite outcome of vascular
death and hospitalization for nonfatal myocardial infarction or nonfatal stroke
between the evening and morning dosing groups over a median follow-up period of
5.2 years.
The evidence from the TIME trial
suggests that dosing time should not be a significant consideration when
advising most patients on managing their blood pressure. This large study showed
that the timing of antihypertensive medication administration is unlikely to
affect major cardiovascular outcomes or mortality rates.
Instead, clinicians should focus on
selecting appropriate medications and supporting adherence to agreed treatment
plans.
Taking medication in the evening
was not harmful but provided no additional benefit versus morning dosing.
Therefore, patients should be advised that they need not change their antihypertensive medication dosing time but might choose to take their medication at a time that suits them best, because the timing makes no difference to cardiovascular outcomes.
CONCLUSION
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.
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Background
Studies have suggested that evening
dosing with antihypertensive therapy might have better outcomes than morning
dosing. The Treatment in Morning versus Evening (TIME) 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
(aged ≥18 years) with hypertension and taking at least one antihypertensive
medication. Eligible participants were randomly assigned (1:1), without
restriction, stratification, or minimisation, to take all of their usual
antihypertensive medications in either the morning (0600–1000 h) or in the
evening (2000–0000 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 were 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
(ie, all participants randomly assigned to a treatment group). Safety was
assessed in all participants who submitted at least one follow-up
questionnaire.
Findings
Between Dec 17, 2011, and June 5,
2018, 24 610 individuals were screened and 21 104 were randomly assigned to
evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry
was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%)
were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African,
Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%]
participants); and 2725 (13·0%) had a previous cardiovascular disease. By the
end of study follow-up (March 31, 2021), median follow-up was 5·2 years, and
529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%)
of 10 601 assigned to morning treatment had withdrawn from all follow-up. A
primary endpoint event occurred in 362 (3·4%) participants assigned to evening
treatment (0·69 events per 100 patient-years) and 390 (3·7%) assigned to
morning treatment per 100 patient-years. No safety concerns were identified.
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
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