Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

May 22, 2023Hypertension (Dallas, Tex. : 1979)

How the timing of blood pressure medicine affects treatment: A review of clinical trials

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Abstract

Evening dosing of antihypertensive drugs significantly reduced ambulatory blood pressure parameters.

Evening dosing resulted in a mean difference of 1.41 mm Hg for 24/48-hour systolic blood pressure and 0.60 mm Hg for diastolic blood pressure.
Night-time systolic blood pressure decreased by 4.09 mm Hg and diastolic blood pressure by 2.57 mm Hg with evening dosing.
Day-time systolic blood pressure showed a smaller reduction of 0.94 mm Hg, while diastolic blood pressure decreased by 0.87 mm Hg.
Numerically lower cardiovascular events were observed with evening dosing compared to morning dosing.
Omitting data from Hermida's trials reduced the observed effects of evening dosing on blood pressure and cardiovascular outcomes.

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BACKGROUND: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening.

METHODS: A PubMed, EMBASE, and clinicaltrials.gov databases search for randomized clinical trials of antihypertensive therapies where patients were randomized to morning versus evening dosing. The outcomes were ambulatory blood pressure (BP) parameters (day-time, night-time, and 24/48-hour systolic blood pressure [SBP] and diastolic blood pressure [DBP]) and cardiovascular outcomes.

RESULTS: Of 72 randomized controlled trials included, evening dosing significantly reduced ambulatory BP parameters: 24/48-hour SBP (mean difference [MD]=1.41 mm Hg; [95% CI, 0.48-2.34]), DBP (MD=0.60 mm Hg [95% CI, 0.12-1.08]), night-time SBP (MD=4.09 mm Hg [95% CI, 3.01-5.16]), DBP (MD, 2.57 mm Hg [95% CI, 1.92-3.22]), with a smaller reduction in day-time SBP (MD=0.94 mm Hg [95% CI, 0.01-1.87]), and DBP (MD=0.87 mm Hg [95% CI, 0.10-1.63]), and numerically lower cardiovascular events compared with morning dosing. However, when controversial data by Hermida (23 trials, 25 734 patients) were omitted (<0.05 for most outcomes), the above effect of evening dosing attenuated with no significant effect on 24/48-hour ambulatory blood pressure, day-time BP, and major adverse cardiac event and smaller reduction in night-time ambulatory SBP and DBP. P heterogeneity

CONCLUSIONS: Evening dosing of antihypertensive drugs significantly reduced ambulatory BP parameters and lowered cardiovascular events but the effect was mainly driven by trials by Hermida group. Unless the intention is to specifically lower night-time BP, antihypertensive drugs should be taken at a time of day that is convenient, optimizes adherence, and minimizes undesirable effects.

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Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

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