Effects of COER‐Verapamil on Circadian Pattern of Forearm Vascular Resistance and Blood Pressure

Controlled-onset extended-release verapamil (COER-V) is designed so drug concentrations rise sharply in the early morning to coincide with the peak incidence of cardiovascular events. The primary objective of this study was to compare the diurnal pattern of forearm vascular resistance (FVR) between hypertensives and normotensives and to determine the effect of COER-V on FVR's diurnal pattern. The authors also studied the effects of COER-V on 24-hour ambulatory blood pressure (ABP) and the early morning blood pressure rise. Baseline 24-hour ABP was recorded, and FVR was determined by venous occlusion plethysmography at 7 a.m., 2 p.m., and 9 p.m. in 23 untreated hypertensives; FVR was also determined in 10 matched, normotensive controls. Plethysmography studies and 24-hour ABP were repeated and S- and R-verapamil concentrations determined over 24 hours by HPLC following > or = 4 weeks of therapy. The diurnal pattern of FVR differed between hypertensives and normotensives, with normotensives exhibiting an FVR decline between 2 p.m. and 9 p.m., while FVR rose at 9 p.m. in hypertensives. COER-V appeared to minimize the diurnal variation in FVR in hypertensives, although there were no significant differences at any single time point (baseline 7 a.m.: 58 +/- 24; 2 p.m.: 48 +/- 13; and 9 p.m.: 55 +/- 19 vs. COER-V at 7 a.m.: 51 +/- 23; 2 p.m.: 51 +/- 17; and 9 p.m.: 54 +/- 17 mmHg/ml/min/100 g). COER-V effectively reduced ABP throughout the 24-hour period (p < 0.05). No significant differences were found in the slopes of the early morning rise in BP or change in morning trough-to-peak BP at baseline and on the drug. The data suggest that hypertension alters the normal diurnal pattern in FVR and that COER-V minimizes the diurnal variation in this parameter. In addition, the authors conclude that COER-V is an effective antihypertensive that lowers BP throughout a 24-hour period, but it does not blunt the early morning rate of BP rise despite peak S-verapamil concentrations in the early morning.