Prazosin GITS vs atenolol in patients with hypertension and normal lipid profile: a randomized, controlled multicenter study. Hyderabad Hypertension Study Group.

OBJECTIVE: To compare the long-term antihypertensive efficacy, tolerability, and metabolic effects of prazosin GITS and atenolol. DESIGN: Randomized, controlled, multicenter study of 26 weeks duration. SETTING: Office practices of 24 physicians in Hyderabad, Andhra Pradesh, 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 a normal lipid profile. 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 atenolol (Tenormin 50-100 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 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: 62 patients randomized to prazosin GITS group and 60 to atenolol group. Of these, 39 in prazosin GITS group (M 23, F 16; mean age-48.4 yr, SEM 1.60) and 39 in atenolol group (M 24, F 15; mean age-42.9 yr, SEM 1.48) completed the entire study. Percent patients with DBP < 90 mm Hg at 24 weeks: prazosin GITS--92.3%, atenolol--92.3%; SBP < 140 mm Hg: prazosin GITS--89.7% atenolol--94.9% both DBP < 90 mm Hg and SBP < 140 mm Hg: prazosin GITS--87.2%, atenolol--89.7%; percent patients with DBP fall of 10 mm Hg or more at 24 weeks: prazosin GITS--92.3%, atenolol--100%. 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 2 groups, except at week 2, when the fall was greater for atenolol (8.8 mm Hg vs 11.4 mm Hg, p = 0.05). Treatment with prazosin GITS resulted in a favourable effect on the serum lipid profile at the end of 24 weeks (p = 0.02 for total cholesterol, p = 0.015 for the ratio of total to HDL cholesterol, p = 0.04 for LDL cholesterol). Atenolol, on the other hand, did not produce any significant change in the metabolic parameters at the end of 24 weeks. Adverse events probably or definitely related to the drug: prazosin GITS--in 10.3% patients, atenolol--in 16.7% patients. CONCLUSION: In the doses used, both prazosin GITS and atenolol had comparable efficacy and tolerability. While atenolol was neutral on serum lipids, prazosin GITS showed a beneficial effect at the end of 24 weeks.

Effects of verapamil and nifedipine on psychomotor performance in human subjects.

The present study was undertaken to evaluate the effects of two structurally dissimilar calcium channel blockers, verapamil (a phenylalkylamine) in a single dose of 40 and 80 mg, and nifedipine (a dihydropyridine) in a single dose of 10 and 15 mg, on psychomotor performance and higher mental functions in human volunteers. Placebo and diazepam (5 mg) were used as negative and positive controls respectively. For evaluating these functions, tests employed were arithmetic ability, visual and auditory reaction time, letter (alphabet) cancellation, rapid fire arithmetic deviation and short term memory for playing cards. Careful record was kept of the heart rate, blood pressure and side effects of the therapy, each time the psychomotor tests were performed. Verapamil, both in 40 and 80 mg dose, was found to impair the performance of subjects to a significant extent in auditory reaction time, letter cancellation and short term memory. These effects were similar to those observed with administration of diazepam. With nifedipine, impairment in performance was observed only in rapid arithmetic deviation test. Thus, calcium channel antagonists, specially verapamil, impaired psychomotor performance of human subjects in our study.