The Use of Confidence Intervals to Describe the Precision of Trough/Peak Ratios for Diltiazem CD in the Treatment of Hypertension

Once‐daily diltiazem hydrochloride, CARDIZEM® CD (diltiazem CD) 300 mg, was evaluated for safety, efficacy, and the relationship between peak and trough antihypertensive ejects 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−6.3 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 ≥ 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 post‐dose. 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. This trial demonstrates diltiazem CD 300 mg is a safe and effective therapy when administered once daily for the treatment of essential hypertension.