Efficacy and safety of 24 weeks of therapy with bendroflumethiazide 1.25 mg/day or 2.5 mg/day and potassium chloride compared with enalapril 10 mg/day and amlodipine 5 mg/day in patients with mild to moderate primary hypertension : a multicentre, randomised, open study

Abstract

Background: The efficacy and safety of therapy with low-dose bendroflumethiazide 1.25 mg/day or 2.5 mg/day and potassium chloride was compared with that of enalapril 10 mg/day and amlodipine 5 mg/day in patients with mild to moderate primary hypertension.

Study design: This was a multicentre study in general practice with patients randomised in a double-blind fashion and on open-label treatment. After a washout phase that lasted 4-6 weeks, 312 patients with a diastolic blood pressure of between 100 and 115 mm Hg were randomised in a double-blind fashion to treatment with either bendroflumethiazide 1.25 mg/day and potassium chloride (n = 117), bendroflumethiazide 2.5 mg/day and potassium chloride (n = 60), amlodipine 5 mg/day (n = 61) or enalapril 10 mg/day (n = 60), all given once daily (numbers in parentheses indicate the intention-to-treat population, with a total of 298 patients). The primary efficacy parameter was the reduction in diastolic blood pressure. Effects on systolic blood pressure, heart rate, biochemical variables, adverse events and quality of life were studied as secondary efficacy parameters.

Results: All treatments reduced diastolic blood pressure significantly; reductions were as follows: 6.8 mm Hg with bendroflumethiazide 1.25 mg/day, 9.1 mm Hg with bendroflumethiazide 2.5 mg/day, 10.8 mm Hg with amlodipine 5 mg/day and 6.8 mm Hg with enalapril 10 mg/day. The reduction in diastolic blood pressure on amlodipine was significantly greater than on bendroflumethiazide 1.25 mg/day and enalapril 10 mg/day (p = 0.013). The percentage of patients achieving a diastolic blood pressure of < 95 mm Hg was 34% (SD 4.4) with bendroflumethiazide 1.25 mg/day, 48% (SD 6.5) with bendroflumethiazide 2.5 mg/day (p = 0.075 vs bendroflumethiazide 1.25 mg/day), 57% (SD 6.3) with amlodipine 5 mg/day (p = 0.004 vs bendroflumethiazide 1.25 mg/day) and 41% (SD 6.4) with enalapril 10 mg/day (p = 0.41 vs bendroflumethiazide 1.25 mg/day) [mean reductions]. The effect on systolic blood pressure was similar with all treatments. No clinically significant changes occurred in heart rate, serum potassium, blood glucose, serum urate or serum cholesterol levels. The incidences of adverse events were similar in the low-dose bendroflumethiazide groups, with significantly higher incidences in the enalapril and amlodipine groups. Quality of life was similar in the different treatment groups, but the study had limited power to detect any difference in this parameter.

Conclusion: The present study has confirmed, in a general practice population, that low-dose bendroflumethiazide (bendroflumethiazide 1.25-2.5 mg/day) in combination with potassium chloride is a well tolerated and efficacious first-line treatment for patients with mild to moderate essential hypertension.