Comparison of nocturnal dosing of diltiazem er and ramipril on early morning blood pressure, heart rate and the rate-pressure product

The early morning is a time of enhanced cardiovascular risk and is associated with steep increases in both blood pressure (BP) and heart rate. Blood pressure control and outcome may be improved by nocturnal dosing of antihypertensive therapy as was recently reported in the HOPE trial. However, little is known about comparative effects of nighttime dosing of antihypertensive therapy. We compared a novel formulation, diltiazem ER, to ramipril, both dosed at bedtime in a multicenter, randomized, double-blind, parallel-group, dose-to-effect study in 261 patients with Stages I-II hypertension. The key efficacy endpoints were changes from baseline in BP, heart rate and the heart rate-systolic BP product (rate-pressure product) measured by ambulatory BP monitoring during the first 4 hours after awakening and for the entire 24-hour period. Patients were randomized to receive either diltiazem ER (240 mg to 360 mg to 540 mg QD; n=130) or ramipril (5 mg to 10 mg to 20 mg QD; n=131) for 10 weeks. Titration of dose occurred when the clinic BP was ≥ 130/85 mm Hg. In both groups, 76% of patients were at the highest dose at the end of 10 weeks of treatment. As shown in the Table, diltiazem ER was associated with significantly greater reductions in mean BP during the first 4 hours after awakening compared to ramipril. The mean reductions in heart rate and rate-pressure product during all time intervals and for the 24-hour mean diastolic BP were also significantly larger (p<0.001 each) for diltiazem ER compared to ramipril. Tolerability and adverse events were similar for the 2 treatment groups. Thus, nocturnal dosing of diltiazem ER was more effective than nocturnal dosing of ramipril in reducing the early morning BP, heart rate and rate-pressure product as well as 24 hour diastolic BP, heart rate, and rate-pressure product.