COMPARISON AND INTERACTION OF LOW-DOSE FELODIPINE AND ENALAPRIL IN THE TREATMENT OF ESSENTIAL-HYPERTENSION IN ELDERLY SUBJECTS

The antihypertensive effect and tolerance of the combined low doses of felodipine and enalapril (5 + 5 mg daily) were compared with those of either drug at a higher dose level (10 mg daily). Our double-blind, three-way crossover study (balanced Latin square design) involved 36 elderly subjects (mean age 67 +/- 6 years) with essential hypertension. After a 4-week placebo run-in phase the subjects were randomized to the active treatment periods, starting with 5 mg felodipine plus 5 mg enalapril, 5 mg felodipine, or 5 mg enalapril daily for the first 4 weeks. The doses in the felodipine and enalapril periods were then doubled for another 2 weeks. All medication was given once daily in the morning, and blood pressure was measured 24 h after a previous dose. The supine blood pressure for subjects given placebo was 178/101 mm Hg. After 6 weeks' treatment systolic and diastolic supine blood pressures were significantly lower with 5 mg felodipine plus 5 mg enalapril (154/85 mg Hg) than with 10 mg felodipine (159/88 mm Hg) or with 10 mg enalapril (162/91 mm Hg), and the diastolic blood pressure was significantly lower with felodipine than with enalapril. At the end of the felodipine plus enalapril, felodipine, and enalapril treatment periods, 75, 69, and 56% of the subjects, respectively, had a supine diastolic blood pressure 90 mm Hg or less. The combination was tolerated better than either monotherapy. The most commonly reported adverse event was swollen ankles, which occurred in one, nine, and five subjects during felodipine plus enalapril, felodipine, and enalapril treatment, respectively. Most adverse events were mild or moderate and only one subject withdrew from the study due to adverse reactions. We observed no clinically significant changes in laboratory variables including blood lipoproteins. A low-dose combination of felodipine and enalapril is a suitable alternative to increased doses of either drug in the treatment of elderly hypertensive patients because of its improved effect and tolerance.