Relation between dose of bendrofluazide, antihypertensive effect, and adverse biochemical effects.
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OBJECTIVE: To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN: Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or placebo for 12 weeks. SETTING: General practices in Zealand, Denmark. PATIENTS: 257 Patients with newly diagnosed or previously treated hypertension, aged 25-70, who had a mean diastolic blood pressure of 100-120 mm Hg after receiving placebo for six weeks. MAIN OUTCOME MEASURES: Reduction in diastolic blood pressure and changes in biochemical variables (potassium, urate, glucose, fructosamine, total cholesterol, apolipoprotein A I, apolipoprotein B, and triglyceride concentrations). RESULTS: All doses of bendrofluazide significantly reduced diastolic blood pressure to the same degree (10-11 mm Hg). Clear relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION: The relevant range of doses of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses. (+info)
Emerging role of calcium-activated potassium channel in the regulation of cell viability following potassium ions challenge in HEK293 cells and pharmacological modulation.
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Severe thiazide-induced hyponatraemia during treatment with enalapril.
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A patient is described who developed mild hyponatraemia on two occasions when treated with bendrofluazide alone, but severe hyponatraemia when treated with the combination of enalapril and bendrofluazide. (+info)
MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.
(30/73)
The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Randomised study of six beta-blockers and a thiazide diuretic in essential hypertension.
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Atenolol was compared with five other beta-blockers and a thiazide diuretic in a randomised cross-over trial of once-daily treatment of essential hypertension. Atenolol was significantly better at reducing resting and exercise blood pressures at 24 hours than any of the other drugs and had a low incidence of side effects. Both timolol and acebutolol had a significant hypotensive effect at 24 hours and a low incidence of side effects, suggesting that further increases in dosage might be effective and well tolerated. Labetalol proved ineffective when given once daily, and the high incidence of side effects, equalled only by pindolol, would probably prohibit further increases in dosage. Bendrofluazide was equal or superior to all the beta-blockers except atenolol at reducing resting blood pressure, and its cheapness still makes it an agent of first choice in mild or moderate essential hypertension. (+info)
Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension. Medical Research Council Working Party on Mild Hypertension.
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Seventeen thousand three hundred and fifty four mildly hypertensive people with diastolic blood pressures between 90 and 109 mm Hg at screening were randomised to active treatment, with bendrofluazide or propranolol, or to placebo tablets. They were followed for a maximum of five and a half years, giving a total of 85,572 patient-years of observation. There were 456 myocardial infarctions or sudden coronary deaths. Drug treatment did not affect the overall rate of coronary events. Rates per thousand person-years were 8.3 and 9.0 in men and 1.8 and 1.7 in women in the active treatment and placebo groups respectively. Event rates were much higher in smokers than in non-smokers on placebo treatment (12.6 and 7.5 in men and 3.5 and 1.0 in women in smokers and non-smokers respectively). An analysis of subgroup results showed a lower event rate in non-smoking men on propranolol than in non-smokers on placebo (5.0 and 7.5 per thousand person-years respectively). Bendrofluazide had no apparent effect on the event rate. The interaction between the type of treatment (propranolol, bendrofluazide, or placebo) and smoking in determining the coronary event rate was not statistically significant, however. The incidence of electrocardiographic changes of silent infarction--that is major Q/QS abnormalities--differed little with sex, smoking habit, or treatment with either active drug. (+info)