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

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.