Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS: Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

A post-marketing acceptability study in 11,685 patients of the efficacy of timolol/bendrofluazide in the management of hypertension in general practice.

A post-marketing acceptability study was performed in 11,685 patients to assess the efficacy and acceptability of 10 mg timolol/2.5 mg bendrofluazide in patients with mild to moderate hypertension in general practice. The initial dose was 1 tablet/day. This was adjusted at weekly intervals up to a maximum of 4 tablets/day or until blood pressures of less than or equal to 95 mmHg diastolic or, in patients of greater than or equal to 60 years, less than or equal to 100 mmHg plus the patient's age (in years) systolic, were achieved. Stabilized patients were followed-up after 12, 24 and 48 weeks. Of the patients enrolled, 69% (8039) were successfully treated for at least 8 weeks, 26% (3033) were withdrawn and 5% (613) defaulted. One tablet/day was required by 61% of patients and 29% required 2 tablets/day to achieve stabilization. The mean reductions in systolic and diastolic blood pressures and pulse rate were 31 and 19 mmHg, and 11 beats/min, respectively. Over 60% of the patients enrolled were still taking timolol/bendrofluazide after 12 months' continuous therapy. The most frequently reported reason for withdrawal was an 'adverse event' which occurred in 15.4% (1805) of patients. Only 1.9% (217) failed to achieve target blood pressure on 4 tablets/day. This large study has shown timolol/bendrofluazide to be a highly effective and acceptable once daily therapy for mild to moderate hypertension in general practice.

Long-term follow-up of 500 patients with mild to moderate hypertension who had successfully completed a 3-month general practice study of a timolol-bendrofluazide combination ('Prestim').

A sample of 500 patients with mild to moderate hypertension, who had been successfully controlled on once daily timolol/bendrofluazide at the end of a 3-month general practice study, was followed up after approximately 1 year of treatment. Physicians who had participated in the trial were questioned on the current status of these patients. Out of 479 reports received, data showed that 358 (75%) patients were still normotensive 47 weeks after starting treatment with timolol/bendrofluazide and in a further 8 patients other antihypertensive agents had been added to this therapy. Of the 113 patients no longer receiving timolol/bendrofluazide, only 38 (7.9%) had stopped therapy due to adverse effects. It is concluded that the results are a further indication that timolol/bendrofluazide offers an acceptable and balanced long-term form of therapy in hypertension for both the patient and the physician.