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Clinical Trial
. 2004 May;6(5):231-41.
doi: 10.1111/j.1076-7460.2004.3624.x.

The antihypertensive efficacy and safety of a chronotherapeutic formulation of propranolol in patients with hypertension

Domenic A Sica  1 , Joel M Neutel, Michael A Weber, Neil Manowitz
Affiliations
Clinical Trial

The antihypertensive efficacy and safety of a chronotherapeutic formulation of propranolol in patients with hypertension

Domenic A Sica et al. J Clin Hypertens (Greenwich). 2004 May.

Abstract

This study evaluated the antihypertensive efficacy and tolerability of a chronotherapeutic formulation of propranolol designed for nighttime dosing (propranolol controlled release [CR]). A total of 434 patients with mild-to-moderate hypertension were randomized to placebo or to one of four doses of propranolol CR (80, 120, 160, or 640 mg/d). At baseline, the mean morning blood pressures were similar in each treatment group and averaged 152/101 mm Hg. After 8 weeks of treatment, morning diastolic blood pressure, the primary efficacy measurement, was significantly reduced from baseline in placebo (-6.98 mm Hg) and all propranolol groups (p<0.001). The decreases ranged from 10.1 mm Hg in the 80-mg/d group to 11.0 mm Hg in the 120-mg/d group and were significantly larger than placebo in the 120-, 160-, and 640-mg/d groups (p<0.05). Blood pressure measured in the evening (trough) demonstrated similar antihypertensive efficacy. Heart rate and rate-pressure product were reduced in a dose-related manner by propranolol CR. The formulation was well tolerated with only fatigue and dizziness being reported more frequently than in the placebo group. Propranolol CR is an effective antihypertensive formulation that may reduce blood pressure during the morning period of maximum cardiovascular risk.

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Figures

Figure 1
Figure 1
Study design schematic. S1=screening visit 1; S2=screening visit 2; S3=screening visit 3; R0=randomization visit at the start of week 1; *time points at which systolic and diastolic blood pressures were measured
Figure 2
Figure 2
Mean morning sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP). Doses were up‐titrated in the propranolol controlled release (CR) formulation 120‐, 160‐, and 640‐mg groups during Weeks 0©2 and were down‐titrated in the same groups during Weeks 8–10. ???=placebo; ???=propranolol CR 80 mg; ???=propranolol CR 120 mg; ???=propranolol CR 160 mg; ???= propranolol CR 640 mg
Figure 3
Figure 3
The effect of propranolol controlled‐release formulation on morning heart rate and rate‐pressure product after 8 weeks of treatment. Pl=placebo; *p<0.001 vs. placebo
Figure 4
Figure 4
Plasma propranolol levels after 4 and 8 weeks of treatment with propranolol controlled‐release (CR) formulation.
See this image and copyright information in PMC

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