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Controlled Onset Extended Release Verapamil At Bedtime May Better Control Morning Blood Pressure, Heart Rate

The administration of controlled onset extended release verapamil at bedtime may control morning blood pressure, heart rate and heart rate systolic blood pressure better than conventional, antihypertensive agents taken in the morning.

Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, when the risk of cardiovascular events is highest.

William B. White, MD, and colleagues at the University of Connecticut School of Medicine, in Farmington, Connecticut, United States, compared the haemodynamic effects of a chronotherapeutic delivery system of verapamil taken at bedtime, versus the conventional morning administration of enalapril or losartan.

The study involved 357 men and women with an untreated sitting diastolic blood pressure of 95 to 114 mm Hg and ambulatory daytime diastolic blood pressure greater than or equal to 85 mm Hg.

The patients were randomized to receive either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of blood pressure, heart rate, and the heart rate systolic blood pressure product were performed by use of 24-hour ambulatory recordings after four weeks of low dose and eight weeks of high dose therapy.

Results were similar at weeks four and eight for all treatment groups, except that the magnitude of change was greater at week eight. After eight weeks of treatment, reductions in early morning blood pressure by COER-verapamil were significantly greater (-15/-10 mm Hg) than enalapril (-9/-7 mm Hg) and losartan (-8/-5 mm Hg), the researchers reported.

COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of blood pressure compared with the other two active treatment groups. Reductions in mean 24-hour blood pressure were greater in patients treated with COER-verapamil compared with those taking placebo or losartan, and was similar to reductions in patients treated with enalapril.

"Bedtime administration of an agent designed to parallel the circadian rhythm of blood pressure and heart rate led to significantly greater early morning haemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning," the researchers concluded.
Am Heart J 2002; 144: 657-665. "Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising."

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