A randomized, controlled, multicenter study to compare prazosin GITS with enalapril in hypertensive patients with diabetes mellitus. Bombay Hypertension Study Group

Abstract

Objective: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and enalapril.

Design: Randomized, controlled, multicenter study of 26 weeks duration.

Setting: Office practices of 20 physicians in Mumbai, India.

Patients: Males and females, aged 30 to 70 yrs, with hypertension of JNC V stage 1 or 2 at the end of a 2-week placebo run-in period, and diabetes mellitus with at least acceptable glycaemic control (FBS < or = 140 mg/dl, 2-hr PMBS < or = 200 mg/dl, and glycosylated hemoglobin < or = 9.5%). Sufficient number of patients recruited so that at least 60 complete the entire study.

Interventions: Prazosin GITS (Minipress XL, 2.5-5 mg once daily) or enalapril (Enam, 5-10 mg once daily) for upto 6 weeks; continued upto 24 weeks in those showing a pre-defined response (SBP and/or DBP normalized, or DBP fall of at least 10 mm Hg with actual value of DBP < 95 mm Hg). Patients allocated to either of the two interventions by randomization.

Outcome measures: Percent patients showing pre-defined BP response at week 6; percent patients with DBP < 90 mm Hg, SBP < 140 mm Hg, and both; percent patients with DBP fall > or = 10 mm Hg; mean fall in BP among those receiving treatment for 24 weeks; mean change in serum lipids at the end of weeks 8, 16, and 24 of treatment; mean change in blood sugar and glycosylated hemoglobin at the end of weeks 8, 16, and 24 of treatment; mean change in 12-hr urinary microalbuminuria and laboratory parameters for safety at the end of week 24; frequency and intensity of adverse events judged probably or definitely related to the drug.

Results: Forty-Eight patients randomized to prazosin GITS group and 41 to enalapril group. Of these, 31 in prazosin GITS group (M 19, F 12; mean age-53.4 yr, SEM 1.68) and 29 in enalapril group (M17, F 12; mean age-54.7 yr, SEM 1.64) completed the entire study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--71.0%, enalapril--72.4%; SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--55.2; both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--54.8%, enalapril--44.8%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--77.4%, enalapril--72.4%. The mean fall in the systolic and diastolic blood pressure from the end-of-placebo-phase values to all the other time points was comparable in the two groups. Treatment with prazosin GITS resulted in a favourable effect on serum triglycerides at the end of 8 weeks (p = 0.017) and 16 weeks (p = 0.011), and no detrimental effect or a marginal beneficial effect on total cholesterol, HDL cholesterol, and LDL cholesterol. Enalapril group, on the other hand, showed a significant increase in LDL cholesterol at the end of 24 weeks (p = 0.018), and a marginal increase in total cholesterol, but a beneficial effect on triglycerides at the end of 16 weeks (p = 0.015). Neither drug had any effect on glycosylated hemoglobin and 12-hr urinary microalbuminuria. Treatment with both drugs was associated with an increase in FBS and 2-hr PMBS, but this rise reached statistical significance only in prazosin GITS group. Adverse events probably or definitely related to the drug: prazosin GITS--2 of 44 patients (4.5%), enalapril--6 of 39 patients (15.4%).

Conclusion: 1. In the doses used, prazosin GITS showed comparable antihypertensive efficacy to enalapril. 2. While enalapril had variable effect, prazosin GITS showed a consistent beneficial effect on some of the serum lipid fractions. 3. The 3-fold difference in the incidence of side effects, although not statistically significant for the available sample size, may be clinically relevant.