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

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.