Beyond Mean Blood Pressure Reduction: Distributional and Responder Effects of Bedtime Antihypertensive Dosing in Nondipping Hypertension. A Secondary Analysis of a Randomized Controlled Study

Q: What are the key findings of this study?

Bedtime antihypertensive dosing reduced 2-month baseline-adjusted clinic systolic blood pressure by 18.1 mm Hg (95% CI -22.4 to -13.8; p < 0.001) compared to morning dosing in nondipping hypertension.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Uncontrolled essential hypertension with a nondipping circadian pattern (n=60). Intervention: Bedtime antihypertensive dosing vs. Continued morning antihypertensive dosing. Primary outcome: Baseline-adjusted 2-month clinic systolic blood pressure (SBP, mm Hg) (MD -18.1 mm Hg, 95% CI -22.4 to -13.8, p=<0.001).

Q: What does this research mean for the field?

Bedtime administration of antihypertensive medication produces greater blood pressure reduction and substantially higher target attainment than morning dosing in patients with uncontrolled nondipping hypertension. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To assess baseline-adjusted clinic blood pressure, target attainment, and distributional changes after bedtime versus morning antihypertensive dosing in uncontrolled nondipping hypertension.

Raymond E Farah; Nicola Luigi Bragazzi; Halil İ̇brahim Ceylan; Nader Ballout; Tony Hanna; Rola Khamisy‐Farah

doi:10.1111/jch.70372

October 1, 2026Journal of Clinical HypertensionOpen Access

Beyond Mean Blood Pressure Reduction: Distributional and Responder Effects of Bedtime Antihypertensive Dosing in Nondipping Hypertension. A Secondary Analysis of a Randomized Controlled Study

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Key result

Bedtime antihypertensive dosing lowers clinic SBP by ~18 mm Hg vs. morning dosing in nondipping hypertension.

MD -18.1 mm Hg
95% CI -22.4 to -13.8
P<0.001
n=60

Figures

Why the study?

Mean blood pressure differences do not fully characterize treatment response to morning versus bedtime antihypertensive dosing, leaving adjusted blood pressure, target attainment, and response distributions less defined.

Does switching antihypertensive therapy from morning to bedtime dosing reduce 2-month clinic blood pressure and improve blood pressure target attainment in adults with uncontrolled nondipping hypertension?

Key Points

To assess baseline-adjusted clinic blood pressure, target attainment, and distributional changes after bedtime versus morning antihypertensive dosing in uncontrolled nondipping hypertension.
Post hoc secondary analysis of a randomized controlled trial comprising 60 patients with uncontrolled hypertension and a nondipping pattern randomized to morning (n=30) or bedtime (n=30) dosing.
Evaluated 2-month clinic systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using baseline-adjusted analysis of covariance along with responder and distributional analyses.
Adjusted 2-month mean differences for bedtime versus morning dosing were -18.1 mmHg for SBP (95% CI -22.4 to -13.8), -11.6 mmHg for DBP (95% CI -14.5 to -8.8), and -13.9 mmHg for MAP (95% CI -16.7 to -11.0; all p < 0.001).
Clinic blood pressure below 140/90 mmHg was achieved by 29 of 30 patients (96.7%) assigned to bedtime dosing compared to 3 of 30 patients (10.0%) assigned to morning dosing (RR 9.67; 95% CI 3.30-28.34; p < 0.001).
Median change differences favored bedtime dosing at -9.5 mmHg for SBP (bootstrap 95% CI -23.5 to 0.5; p = 0.025) and -3.0 mmHg for DBP (bootstrap 95% CI -16.0 to 2.5; p = 0.077), though confidence intervals spanned zero.

Study Design

Type

RCT (n=60)

Blinding

Open-label

Randomization

1:1 parallel-group randomization

Multicenter

No

Structured PICO

Does switching antihypertensive therapy from morning to bedtime dosing reduce 2-month clinic blood pressure and improve blood pressure target attainment in adults with uncontrolled nondipping hypertension?

P

Population

60 non-obese adults with uncomplicated, uncontrolled essential hypertension and a nondipping ambulatory BP profile, free of target-organ damage or systemic disease, followed for 2 months.

I

Intervention

Moving existing antihypertensive regimen (mostly long-acting calcium-channel blocker or angiotensin-converting enzyme inhibitor; minority on combination therapy) from morning to bedtime administration without a planned change in drug or dose for 2 months.

C

Comparator

Continued morning administration of existing antihypertensive regimen without a planned change in drug or dose (80% received monotherapy, mostly a long-acting calcium-channel blocker or angiotensin-converting enzyme inhibitor) for 2 months.

O

Outcome

Baseline-adjusted difference in mean 2-month clinic blood pressure (systolic BP, diastolic BP, and mean arterial pressure) measured via repeated seated clinic measurements.surrogate

Main Result

Mean Difference: -18.1 (95% CI -22.4–-13.8)

Absolute Event Rate: 131.5% vs 149.2%

p-value: p=<0.001

In patients with uncontrolled nondipping hypertension, shifting unchanged antihypertensive medication from morning to bedtime significantly lowered 2-month adjusted clinic blood pressure and increased the attainment of clinic blood pressure <140/90 mm Hg, supporting further study of phenotype-guided chronotherapy.

Limitations

Post hoc secondary analysis with responder thresholds not prespecified as primary outcomes
Short follow-up duration limited to 2 months
Reliance on clinic blood pressure which is a surrogate endpoint rather than cardiovascular outcomes or repeat 24-hour ambulatory control
Small sample size (30 patients per group) resulting in imprecise responder, distributional, and subgroup estimates
Single-center design excluding obesity, smoking, systemic disease, and target-organ damage, limiting generalizability
Post hoc secondary analysis with responder thresholds not specified as primary outcomes in the original study
Short follow-up duration limited to 2 months and reliance on clinic BP, which is a surrogate rather than a cardiovascular endpoint
Small sample size (30 patients per group) resulting in imprecise responder and subgroup estimates
Single-center design excluding obesity, systemic disease, smoking, and target-organ damage, limiting generalizability to contemporary multimorbid hypertensive populations
Clinic BP below 140/90 mm Hg does not establish sustained control throughout the full 24-hour cycle

Implication

Supports bedtime dosing in nondipping hypertension; extends neutral large trials by targeting this phenotype.

Abstract

Mean blood pressure (BP) differences do not fully characterize treatment response. We examined adjusted BP, target attainment and change distributions after morning versus bedtime antihypertensive dosing. This post hoc secondary analysis of a randomized controlled trial included 60 patients with uncontrolled hypertension and a nondipping pattern, assigned to morning or bedtime dosing (30 per group). Two-month systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) were compared using baseline-adjusted analysis of covariance. Secondary analyses assessed BP <140/90 mmHg and median and trimmed changes. Adjusted bedtime-minus-morning differences were -18.1 mmHg for SBP (95% CI -22.4 to -13.8), -11.6 mmHg for DBP (-14.5 to -8.8) and -13.9 mmHg for MAP (-16.7 to -11.0); all p < 0.001. Bootstrap intervals were similar. BP <140/90 mmHg was achieved by 29/30 (96.7%) versus 3/30 (10.0%) patients (risk ratio 9.67; 95% CI 3.30-28.34). Median SBP and DBP change differences were -9.5 and -3.0 mmHg, respectively, with confidence intervals including zero. Bedtime dosing was associated with lower adjusted two-month BP and greater target attainment. Change-based estimates were less precise, indicating uncertainty about the distribution of response. These exploratory findings from a small randomized trial warrant prospective confirmation.

Discussion

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Cite This Study

Farah et al. (2026) conducted an RCT in Uncontrolled essential hypertension with a nondipping circadian pattern (n=60). Bedtime antihypertensive dosing vs. Continued morning antihypertensive dosing was evaluated on Baseline-adjusted 2-month clinic systolic blood pressure (SBP, mm Hg) (MD -18.1 mm Hg, 95% CI -22.4 to -13.8, p=<0.001). Bedtime antihypertensive dosing reduced 2-month baseline-adjusted clinic systolic blood pressure by 18.1 mm Hg (95% CI -22.4 to -13.8; p < 0.001) compared to morning dosing in nondipping hypertension.

synapsesocial.com/papers/6ae13cd1043bfbd6353325de https://doi.org/10.1111/jch.70372

Topics

Hypertension management

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Beyond Mean Blood Pressure Reduction: Distributional and Responder Effects of Bedtime Antihypertensive Dosing in Nondipping Hypertension. A Secondary Analysis of a Randomized Controlled Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Beyond Mean Blood Pressure Reduction: Distributional and Responder Effects of Bedtime Antihypertensive Dosing in Nondipping Hypertension. A Secondary Analysis of a Randomized Controlled Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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