COMPARISON OF THE FIXED COMBINATION OF ENALAPRIL DILTIAZEM ER AND THEIR MONOTHERAPIES IN STAGE-1 TO STAGE-3 ESSENTIAL-HYPERTENSION/

The safety and efficacy of two fixed dose combinations of enalapril an d diltiazem extended release formation (ER) (E/D) were compared with t heir monotherapies and placebo in patients with stage 1 to 3 hypertens ion. The trial design was a multicenter, randomized, double blind, pla cebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting dias tolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly as signed to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, en alapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/ diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 +/- 2 h postdose) s itting blood pressure measurements at week 12 and at the end of the op en label part of the study. Safety was evaluated based on patient symp toms, clinical laboratories, and electrocardiograms (EGG). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, resp ectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 sig nificantly reduced trough sitting systolic blood pressure (-7.9 and -9 .0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus plac ebo. E/D effectively lowered SiDBP and SiSBP during the open label ext ension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fati gue, cough, rash, and impotence. The event frequency for the combinati ons were similar to those seen with the monotherapies. Fixed combinati ons of E/D were generally well tolerated, with an increased blood pres sure lowering effect as compared with the individual components in pat ients with stage I to III hypertension. (C) 1998 American Journal of H ypertension, Ltd.