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Biomedical subjects

F Forette

Publications and source records attributed to F Forette.

At least 55 records · Page 3Linked to original sources

Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.

A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.

Actuarial Analysis

Effect of nicardipine in elderly hypertensive patients.

The purpose of this study was to test tolerance and the antihypertensive effect of nicardipine, a new calcium antagonist, in 31 elderly patients aged 57-95 years. The study was conducted as a double-blind trial. The patients were allocated randomly to either active or placebo treatment. Sixteen patients were given 10-30 mg of nicardipine three times a day (mean dose, 69.4 mg per day); 15 other patients received a matching placebo. After 4 weeks, nicardipine lowered mean blood pressure, and the changes in systolic and diastolic blood pressure were significantly greater in the nicardipine group than in the placebo group. Nicardipine was tolerated very well, and orthostatic hypotension was never observed. There was no change in heart rate. Plasma renin activity (PRA) was measured in eight patients. There was no correlation between PRA and the antihypertensive effect of nicardipine. A pharmacokinetic study performed in 15 elderly patients showed a fast rate of absorption and also higher plasma levels than those observed in hypertensive adults (mean age, 54 years). This trial demonstrates the effectiveness of nicardipine in elderly hypertensive patients.

Age Factors

[Treatment of arterial hypertension in the aged with a calcium antagonist: nicardipine].

The purpose of this study was to test in double-blind trial the tolerance and antihypertensive effect of nicardipine versus placebo in 32 elderly patients (mean age: 84 years). Nicardipine was given three times a day (mean dose: 69.4 mg per day). After four weeks, nicardipine lowered blood pressure (BP) from 186 +/- 4 mmHg/99.5 +/- 3 mmHg to 150 +/- 6/84 +/- 3 mmHg (p less than 0.001). 10 out of 16 patients were normalized (BP less than 160-95 mmHg). The placebo group remained hypertensive: 181 +/- 7/96 +/- 4 mmHg versus 183 +/- 4/101 +/- 3 mmHg (NS). 3 placebo treated patients were nevertheless normalized. The changes in systolic BP and diastolic BP were significantly greater in the Nicardipine group: respectively -36 +/- 4 versus -2 +/- 6 mmHg (p less than 0.001), -16 +/- 3 versus -5 +/- 4 mmHg (p less than 0.05). Treatment was very well tolerated. Orthostatic hypotension, change in heart rate, variation in biological parameters were never observed. These data agree with Buhler's statement suggesting that calcium channel inhibitors can represent an interesting alternative to diuretics as first line monotherapy in the treatment of hypertension in the elderly.

Aged

[Risk of cerebrovascular accident in the aged hypertensive subject. Results of a 10-year longitudinal survey].

A ten year longitudinal survey of 191 female elderly subjects (mean age 80 - Range 61 to 101 years) was set up to demonstrate that even a moderate isolated systolic hypertension is a powerful contributor to the incidence of cerebrovascular complications in the elderly. The incidence of cerebrovascular events was carefully recorded and was correlated with a number of parameters registered at entry into the study. The results show that isolated systolic hypertension as well as diastolic hypertension is significantly correlated to the incidence of strokes independently of other parameters (Blood Cholesterol, Blood Sugar) which do not appear in this population as risk factors of cardiovascular morbidity. This underlines the high interest of controlled therapeutic studies run in this field in elderly patients.

Aged

A pharmacokinetic study of acebutolol in aged subjects as compared to young subjects.

Pharmacokinetics of acebutolol have been studied in hypertensive aged patients (79.4 +/- 3.8 years) and in young healthy subjects (23.4 +/- 0.7 years) after intravenous (0.35 mg/kg bolus) and oral administration (400 mg). Acebutolol and diacetolol, the main metabolite, plasma levels were determined by high-pressure liquid chromatography. After intravenous administration, apparent volume of distribution (1.5 vs. 2.4 liter . kg-1, p less than 0.05) and total body clearance (6.2 vs. 8.8 ml . min-1 . kg-1, n.s.) of acebutolol are smaller in elderly than in young men. After oral administration, maximum plasma levels (28.03 vs. 9.68 micrograms . l-1 . kg-1) and area under the curve (163.1 vs. 57.5 micrograms . l-1 . h . kg-1) are significantly higher in aged patients than in young subjects (p less than 0.001). Acebutolol and diacetolol plasma half-lives increase in elderly patients (11.6 vs. 7.2 h and 14.8 vs. 12 h respectively). These results suggest a possible accumulation of acebutolol and diacetolol in elderly.

Acebutolol

Antihypertensive therapy in patients above age 60 with systolic hypertension. A progress report of the European Working Party on High Blood Pressure in the Elderly (EWPHE).

1. Although systolic blood pressure elevation is responsible for increased incidence of cardiovascular accidents in old people, the preventive benefit of lowering systolic hypertension in elderly has not been confirmed. 2. A double blind study comparing the effects of a placebo and of an active regimen (hydrochlorothiazide-triamterene with or without methyldopa) in people over 60 years with isolated systolic hypertension has been undertaken by the European Working Party on High blood pressure in the Elderly (EWPHE). 3. The actively treated group shows a lowered sitting blood pressure (-15/6 mm Hg), a mild increase of serum creatine, serum uric acid and blood glucose and a mild decrease of serum potassium after two years of treatment when compared to the spontaneous changes observed in the placebo treated group. 4. The study is continuing to evaluate if the blood pressure reduction prevents or reduces the incidence of cardiovascular accidents, although some biochemical changes were provoked by the treatment.

Aged

The prognostic significance of isolated systolic hypertension in the elderly. Results of a ten year longitudinal survey.

A ten year longitudinal survey of 191 female elderly subjects (mean age 80--Range 61 to 100 years) was set up to demonstrate that even a moderate isolated systolic hypertension is a powerful contributor to the incidence of cardiovascular complications in the elderly. The incidence of all cardiovascular events was carefully recorded and was correlated with a number of parameters registered at entry into the study. The results show that isolated systolic hypertension as well as diastolic hypertension is significantly correlated to the incidence of strokes and myocardial infarction independently of other parameters (Blood Cholesterol, Blood Sugar) which do not appear in this population as risk factors of cardiovascular morbidity. This underlines the high interest of controlled therapeutic studies run in this field in elderly patients.

Blood Pressure

Influence of anti-hypertensive therapy on serum cholesterol in elderly hypertensive patients. Results of trial by the European Working Party on High blood pressure in the Elderly (EWPHE).

In the European Working Party trial on High blood pressure in the Elderly, patients over 60 are randomly allocated either to receive diuretic capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene or matching placebos. If the blood pressure remains high those receiving active diuretic treatment also receive methyldopa. Those receiving a placebo diuretic area given placebo methyldopa tablets. The study is double blind, started in 1974 and is still in progress. Three hundred and thirty-one patients have now been followed for 1 year and of these 190 have been followed for 2 and 90 for 3 years. After 1 year the serum cholesterol in the placebo group fell by an average of 10.4 mg/100 ml; over 2 years the fall was 16.0 mg/100 ml and over 3 years 20.8 mg/100 ml (6.7%). The corresponding results for the actively treated group were falls of 3.1 mg/100 ml; 20.3 mg/100 ml and 17.3 mg/100 ml (6.6%). Over a period of up to 3 years the average fall in cholesterol was 5.9 mg/100 ml/year in the placebo group and 5.0 mg/100 ml/year in the actively treated group. Thus the changes in serum cholesterol were similar whether the patients received active or placebo medication. In particular there was no evidence for an increase in cholesterol nor for a smaller decrease during diuretic therapy. In the actively treated group the fall in blood pressure in the more hypertensive patients was accompanied by a fall both in haematocrit and serum cholesterol. In patients with less severe hypertension, active treatment was not accompanied by a fall in either hematocrit or cholesterol. These different responses of serum cholesterol in the more and less severe hypertensives in the present study could explain some of the previous conflicting reports on the influence of diuretic treatment on serum cholesterol.

Aged

Pharmacokinetics of amitriptyline in the elderly.

The pharmacokinetics of amitryptyline (AMI) have been evaluated in six healthy elderly volunteers (72-83 years of age) after a single dose of 125 mg of AMI-HCl. AMI was absorbed rather slowly (mean peak time 10.4 +/- 1.6 hrs) but very efficiently (F: 0.59-0.75). The rate of formation of nortriptyline (NT) as well as the appearance clearance values (0.18-0.45 l/h/kg) of AMI were significantly lower than those previously described for younger subjects. Reversible alterating ECG were observed in 5 cases concomitantly with AMI peak plasma concentrations. The results indicate the desirability of reduced and/or divided daily doses of AMI in the elderly.

Aged

[Treatment of arterial hypertension in the elderly with an alpha-blocker: nicergoline (author's transl)].

The tolerance and anti-hypertensive activity of nicergoline, an alpha-adrenoceptor blocking agent, were studied in 28 hypertensive subjects older than 65 years (mean age: 84 years). The trial was conducted double-blind: 14 subjects were given nicergoline 30 mg/day divided into 6 doses ("lyocs"), and 14 subjects received a placebo identical in appearance with the drug. A mean decrease of 34 mm Hg in systolic arterial pressure (p < 0.001) and of 16 mm Hg in diastolic arterial pressure (p < 0.001) was observed in subjects under nicergoline. The corresponding changes in blood pressure (-12 and -7.9 mm Hg respectively) in subjects under placebo were not significant. No side-effect requiring discontinuation of treatment was encountered. The remarkable effectiveness and tolerance of nicergoline make it a highly suitable agent for the treatment of hypertension in elderly people.

Aged

Comparison of single-dose pharmacokinetics of imipramine and maprotiline in the elderly.

Pharmacokinetic profiles of imipramine and a newer tetracyclic antidepressant, maprotiline, were studied in elderly (75-83 years of age) subjects who were given a single oral dose of 125 and 175 mg, respectively, of these drugs. The apparent elimination half-life of imipramine was 20.8-34.9h (means 26.4h), its biovailability (F) was 40-64% (means 57%), and the apparent plasma clearance was from 0.27-0.57h/kg (mean 0.41h/kg). Maprotiline had a longer half-life (mean 31.5h range 20.6-51.8h, but its bioavailability (mean 50%) and plasma clearance (mean 0.49h/kg) values were in the range similar to those seen after imipramine. It appears that the elimination half-life of imipramine is longer and its plasma clearance is markedly reduced in elderly subjects when compared to values reported in young adults. Subjective clinical side effects were minimal with the two drugs. However, alterations in heart rate, blood pressure, or electrocardiogram occurred in all subjects. This suggests that caution should be exercised before initiating and during the treatment of elderly patients with these antidepressant drugs.

Aged

[The treatment of hypertension in the elderly using a beta-blocker: acebutolol (author's transl)].

The tolerance and antihypertensive action of acebutolol, as a sole drug and in combination with a diuretic, were studied in a population of 34 female subjects aged over 65 years, with a mean of 81 years, suffering from well tolerated essential hypertension. The study was carried out in the form of double blind permutations, each subject receiving successively in an order determined by random selection each of three therapeutic phases: acebutolol, acebutolol in combination with a diuretic and a placebo. The results showed that in the elderly acebutolol had a moderate diuretic action which was remarkably potentialised by diuretics. The tolerance of this beta-blocker was excellent: no cases of cardiac failure, and no disturbances in atrioventricular conduction developed during the phases with active treatment.

Acebutolol

Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly.

119 elderly, hypertensive patients were followed-up for 1 year and 48 for 2 years in a double-blind, randomised, controlled trial in which they received either placebo or 25-50 mg hydrochlorothiazide and 50-100 mg of triamterene daily. Half of the active treatment group also received 250 mg to 2 g methyldopa daily. After 2 years the active treatment group had an average increase in fasting blood-sugar of 9.6 mg/dl compared with an average fall of 3.1 mg in the placebo group (p less than 0.001). Blood-glucose rose by an average of 26.6 mg/dl in the active group when determined 1 hour after 50 g oral glucose and decreased by an average of 5.3 mg/dl in patients who had been on placebo for two years (p less than 0.05). The hyperglycaemic effect of diuretics appeared to be related to potassium loss since, in both groups, impairment of glucose tolerance was most marked in those in whom the serum-potassium decreased over the 2 years.

Aged

Antihypertensive therapy in patients above age 60. Third interim report of the European Working Party on High blood pressure in Elderly (EWPHE).

Three hundred forty nine hypertensive patients above the age of 60 have entered the double-blind multicentre trial of the European Working Party on High blood pressure in the Elderly (EWPHE). After stratification and randomisation half were treated with one or two capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene and if blood pressure control was insufficient methyldopa was added up to 2 g daily; the other half received matching placebo. No significant differences between the groups were present prior to randomisation. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during two years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. However, during the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained for two years. Also glucose tolerance was impaired after 2 years in the actively treated group. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. But this benefit must be proven by observed statistical differences in terminating events between the groups. Therefore the patients are being followed for a longer period of time and more patients are admitted into the trial.

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