ABSTRACT
Once-daily diltiazem hydrochloride, CARDIZEM CD (diltiazem CD) 300 mg, was evaluated for safety, efficacy, and the relationship between peak and trough antihypertensive effects in a multicenter, placebo-controlled, parallel design trial. After a 4- to 6-week placebo baseline period, 111 patients with essential hypertension were randomized to receive placebo or diltiazem CD for a 4-week treatment period. Diltiazem CD 300 mg lowered supine diastolic and systolic blood pressure at trough significantly more than placebo (-7.5 mm Hg vs. -1.3 mm Hg, P = 0.0001 and -6.4 mm Hg vs. 0.5 mm Hg, P = 0.0051, respectively). Supine blood pressure was also measured hourly from 6 to 10 hours after the dose to assess peak effect and trough/peak ratios. Using the largest residual drug effect of -8.3 mm Hg at 6 hours as peak and the 24-hour residual drug effect of -5.9 mm Hg as trough, the trough/peak ratio was estimated to be 71%, with a lower one-sided 95% confidence limit of 50%. The precision of the trough/peak ratio is estimated by the lower confidence limit of 50%, which establishes the trough/peak ratio as statistically > or = 50%. No statistically significant differences in supine DBP were noted between the peak effect hours, indicating a plateau of the peak antihypertensive effect from 6 to 10 hours postdose. Diltiazem CD therapy was well tolerated, with no serious treatment-related adverse events reported during the trial and no patients discontinuing the trial due to a treatment-related adverse event.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Blood Pressure/drug effects , Diltiazem/therapeutic use , Hypertension/drug therapy , Adult , Confidence Intervals , Diltiazem/administration & dosage , Diltiazem/pharmacology , Double-Blind Method , Drug Administration Schedule , Female , Heart Rate/drug effects , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To critically evaluate the current literature regarding the role of calcium-channel antagonists in preventing atherosclerosis. DATA SOURCES: English language clinical studies, abstracts, conference proceedings, and review articles pertaining to calcium-channel antagonists and atherosclerosis. STUDY SELECTION: Relevant animal and human studies examining the role of calcium-channel antagonists in atherosclerosis prevention and treatment. DATA EXTRACTION: Potential mechanisms for the development of atherosclerosis and the use of calcium antagonists for preventing and treating coronary artery disease are discussed. Animal studies are summarized; next, significant data from human clinical studies are presented. DATA SYNTHESIS: Available studies are described and discussed. CONCLUSIONS: Results from animal and clinical trials in humans suggest that calcium antagonists may retard the development and progression of atherosclerosis. However, most clinical trials to date have been conducted in patients with proven atherosclerotic plaques. Further studies examining the role of calcium-channel antagonists in preventing and treating atherosclerosis are needed, but may be difficult to conduct because of the large numbers of patients required, long trial duration, and associated costs.
