Different drug classes have variable effects on blood pressure depending on the time of day

Blood pressure (BP) is controlled by a variety of systems, the activities of which vary throughout the day. As drugs are developed that selectively block these systems, the fall in BP may not be consistent over 24 h.

A total of 24 patients (aged >65 years) with systolic BP (SBP; >150 mm Hg) that had not been treated entered a substudy of a larger study performed in 74 patients. In a double blind, crossover study with a balanced design, they received placebo, atenolol 50 mg, perindopril 8 mg, felodipine 10 mg, or hydrochlorothiazide 50 mg. The study periods were 2 months. Ambulatory BP monitoring was performed at the end of each period, and was divided into awake periods (9:00 AM to 10:00 PM), sleep periods (12:00 AM to 6:00 AM), and morning periods (6:00 AM to 9:00 AM). Medication was taken at 9:00 AM.

The four drug classes lowered 24-h mean SBP (P <.05), but the fall with atenolol was less than with the other drugs. The fall in awake BP with perindopril was less than with felodipine or hydrochlorothiazide. Atenolol caused no significant fall in sleep or morning SBP, and the falls with the other three drugs were significant and were greater than the fall with atenolol. The fall in sleep BP with perindopril was greater than with the other drug classes. The awake-sleep difference in SBP increased with perindopril, stayed the same with felodipine and hydrochlorothiazide, and was reduced by atenolol.

In this study, the response to the different drug classes differed. The response to drugs that work relatively nonspecifically (diuretics, calcium blockers) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems. This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day.