title: Comparison of effects of controlled onset extended release verapamil at bedtime and nifedipine gastrointestinal therapeutic system on arising on early morning blood pressure, heart rate, and the heart rate-blood pressure product.
abstract: We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.
authors.affiliation: Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington 06032-3940, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: White
authors.forename: H R
authors.initials: HR
authors.lastname: Black
authors.forename: M A
authors.initials: MA
authors.lastname: Weber
authors.forename: W J
authors.initials: WJ
authors.lastname: Elliott
authors.forename: B
authors.initials: B
authors.lastname: Bryzinski
authors.forename: T D
authors.initials: TD
authors.lastname: Fakouhi
mesh_terms: D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D019454:Chronotherapy; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D009543:Nifedipine / Q000008:administration & dosage*; D014700:Verapamil / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D014700:Verapamil; D009543:Nifedipine