Evaluation of blood pressure response to the combination of Enalapril (single dose) and Diltiazem ER (four different doses) in systemic hypertension

Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination. A 6-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in essential hypertensive patients (diastolic blood pressures [BP] when seated, 95-115 mm Hg) to evaluate the efficacy, dose response, and safety profiles of enalapril combined with a new once-daily formulation of diltiazem. BP and heart rate were measured at 5 (peak) and 24 (trough) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily. There were 336 patients randomly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER (60, 120, 180, or 240 mg), enalapril 5 mg alone, or placebo, Each combination dose level produced statistically significant reductions (p < 0.05) in trough diastolic BP when seated, compared with placebo (-6.8, -8.3, -10.1, and -10.3 mm Hg for the diltiazem ER doses of 60, 120, 180, and 240 mg, respectively). The 3 highest combination dose levels resulted in statistically significant (p < 0.05) decreases in trough systolic BP when seated, compared with placebo. There was a significant (p < 0.001) linear dose-response relation. A trough-to-peak ratio greater than or equal to 0.5 was shown for the 3 highest combination doses. Drug-related adverse events were seen in 8.9% to 19% of the combination patients, 14.3% of the enalapril patients, and 8.6% of the placebo patients. The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy.