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Biomedical subjects

F Forette

Publications and source records attributed to F Forette.

At least 37 records · Page 2Linked to original sources
PubMed1989

Value of angiotensin converting enzyme inhibitors in the elderly: the example of perindopril.

The efficacy and safety of perindopril in hypertension (HT) in the elderly have now been clearly demonstrated. In a randomized, double-blind placebo-controlled study conducted in 34 patients with a mean age of 84 years, we observed a significant reduction in systolic blood pressure (SBP) by 10% (p less than 0.001) and in diastolic blood pressure (DBP) by 9% (p less than 0.01) in the perindopril group. In the placebo group, the reduction observed was 5% and 4% respectively, although the difference between the two groups was not significant. The clinical and laboratory safety was satisfactory. However, in the treated group, there was a significant increase in serum potassium (p less than 0.01), which nevertheless remained within normal limits. An open study conducted in 91 patients with a mean age of 79.1 years, followed over a period of 6 months, confirmed the very good acceptability of the drug, despite the transient reduction in creatinine clearance observed in one female patient. The efficacy, evaluated less reliably in an open study, appeared to be excellent as 92.5% of patients were controlled by the end of treatment. In a study in healthy subjects, Reid observed a more intense effect on blood pressure (BP) in elderly subjects, which could be partly explained by a higher blood pressure level and by earlier and more prolonged converting enzyme inhibition (not significant). The practical value of this angiotensin converting enzyme (ACE) inhibitor, related to its efficacy and safety, is reinforced by a theoretical value: its action on arterial compliance, its beneficial effect on cardiac function, its potential action on the renin-angiotensin system of the brain, the structural modifications induced in the arterial wall open extremely stimulating prospects in the field of aging.

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PubMed1987

Rationale for ACE inhibition in the elderly: treatment of arterial hypertension with enalapril.

A randomized, double-blind, placebo-controlled trial was conducted with 32 elderly patients (aged 75-97 years) with uncomplicated essential hypertension, to evaluate the efficacy and tolerance of enalapril, an angiotensin-converting enzyme inhibitor. It was given over an 8-week period in doses from 20 to 40 mg/day and was compared with an identical placebo. Enalapril caused a significant reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by the 2nd week, an effect that persisted through to the 8th week (190 +/- 16/102 +/- 7 to 151 +/- 19/85 +/- 11 mm Hg); 67% of patients had their pressures normalized (less than 160/95 mm Hg). BP was also significantly decreased by the 8th week under placebo (183 +/- 16/101 +/- 9 to 165 +/-21/91 +/- 13 mm Hg), but only 35% of patients attained a normal pressure. Heart rate did not change with treatment. Enalapril caused an increase in plasma renin activity (1.22 +/- 0.08 to 3.66 +/- 2.50 ng/ml/h), whereas aldosterone levels remained unchanged. There was a mild, significant elevation of creatinine level with enalapril but other laboratory parameters, including serum potassium, were unaltered. Two deaths occurred in the enalapril group, but were not considered to be treatment-related. The drug was otherwise well tolerated. Serum enalapril concentration was assessed in 10 patients taking 20 mg/day over an 8-day period. At equilibrium, the level was 22.3 +/- 5.0 ng/l and it correlated both with converting enzyme inhibition and with renal function. Enalapril is shown to be an effective and well-tolerated antihypertensive medication in elderly patients.

Age Factors↗
PubMed1987

[Nosologic framework of mental deterioration in aged subjects. From clinical practice to epidemiology].

The difficulty of defining a precise nosologic framework for mental decline is linked, on the one hand, to the contradictions surrounding the term normalcy as age increases, and, on the other, to the fact that mental decline has been mired for years under a term that must be definitively proscribed: "psycho-compartmental disorders of senescence". In this catch-all++ proscribed: "psycho-compartmental disorders of senescence". In this catch++-all it is, in fact, essential to identify diseases whose nature, prognosis and, above all, therapeutic approaches differ fundamentally one from the other; to confuse them is to risk dramatic consequences. Standardization of diagnostic criteria through the combined use of clinical data, the DSM III classification, scored tests (MMS, Hachinsky, etc.), as well as scannography, presently makes it possible to arrive at the diagnosis of dementia with reasonable accuracy. This standardization++ has its limits and is not necessarily useful in atypical cases. It is nevertheless an indispensable tool for epidemiological studies and therapeutic trials.

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PubMed1987

[Arterial hypertension in the elderly. Double-blind study versus placebo of the efficacy and tolerability of an alpha-beta blocker: labetalol].

The purpose of this study was to investigate the efficacy and safety of labetalol, an alpha and beta-adrenergic receptor blocking agent in 32 patients aged from 72 to 97 years (mean = 85 years) with blood pressure (B.P.) greater than or equal to 160/95 mmHg. This study was carried out in a double-blind, randomized, placebo-controlled design. After 6 weeks of treatment with labetalol (mean dose = 235 +/- 47.5 mg/day), the systolic pressure was lowered from 187 +/- 24 to 145 +/- 28 mmHg (p less than 0.001) and the diastolic pressure from 98 +/- 10 to 82 +/- 9 mmHg (p less than 0.001). Likewise, in the placebo group, both systolic and diastolic pressures were significantly reduced but the changes were significantly greater in the labetalol group, -33 +/- 26 versus -13 +/- 20 mmHg and -14 +/- 10 versus -8 +/- 14 mmHg respectively. Labetalol achieved B.P. control (160/95 mmHg) in 64% of the treated patients, compared to 40% in the placebo group. Two patients on labetalol discontinued their treatment due to side-effects (one bradycardia and one cutaneous reaction) compared with one patient on placebo (cardiac failure). Two other cases in the labetalol group had side-effects (one fatigue and one dizziness) which prevented increasing the treatment as necessary.

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PubMed1986

Efficacy of antihypertensive drug treatment according to age, sex, blood pressure, and previous cardiovascular disease in patients over the age of 60.

Results of the European Working Party on High Blood Pressure in the Elderly (EWPHE) trial have been analysed in relation to age, sex, blood pressure, and previous cardiovascular disease. Cardiovascular mortality and the cardiovascular study-terminating events were significantly and independently related to treatment, age, cardiovascular complications at randomisation, and systolic but not diastolic blood pressure. The benefits of treatment observed in the trial seemed to be independent of entry blood pressure and the presence or absence of cardiovascular complications at entry. There was some evidence that treatment effect decreases with advancing age. Little or no benefit from treatment could be demonstrated in patients over the age of 80 years, the great majority of whom were women.

Age Factors↗
PubMed1986

Glucose intolerance during diuretic therapy in elderly hypertensive patients. A second report from the European Working Party on high blood pressure in the elderly (EWPHE).

Five hundred and seven elderly hypertensive patients were followed for 1 year, 371 for 2 years and 270 for 3 years in a double-blind, randomized, controlled trial in which they received either placebo or 25-50 mg hydrochlorothiazide and 50-100 mg of triamterene daily. One third of the active treatment group also received 250 mg to 2 g methyldopa daily. After 1 year the active treatment group had an average increase in fasting blood sugar of 2.5 mg/dl compared with an average fall of 1.4 mg/dl in the placebo group (P = 0.01). The increase in blood sugar 1 hour and 2 hours after 50 g oral glucose tended to be greater in the actively treated group but these increases did not achieve statistical significance. The effects of diuretic treatment were established after one year and did not increase further over the next 2 years. Overall there was an increase in fasting blood sugar of 5 mg/dl in the active treatment group which occurred mainly in the first year. The hyperglycaemic effect of diuretics appeared to be partly or wholly related to potassium loss since, in both groups, impairment of glucose tolerance was most marked in those in whom serum potassium decreased. The measures of blood sugar were also positively related to systolic pressure before and after treatment.

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PubMed1986

[Neuropathological study of 12 centenarians: the incidence of Alzheimer type senile dementia is not particularly increased in this group of very old patients].

The brains of 12 patients aged more than 100 years were studied neuropathologically. These were all women who had been long-stay patients at the Charles Foix Hospital, Ivry. On the basis of a retrospective examination of the clinical records the patients were classified as demented or non-demented. No attempt was made to evaluate their mental status more precisely because of the prevalence of deafness (in 10) and blindness (in 7) and also because of the difficulty in assessing mild cognitive changes in institutionalized patients. Three patients were considered to have been demented according to the criteria of the DSM3 (1980). In the brain of one demented case the pathology was that of Alzheimer's disease, in one there were multiple infarcts and in the third there were both senile and vascular changes. The findings in this study are in accordance with the reports of others and indicate that the incidence of senile dementia of the Alzheimer type is not increased in people of very advanced age. Neuropathological findings included reduced brain weight; neurofibrillary tangles in hippocampal neurons of every case as well as in neocortical neurons (absent from neurons of the substantia innominata in only 1 case); senile (neuritic) plaques were found commonly in the hippocampus, less so in neocortical areas (senile plaques totally absent in only one case); granulovacuolar degeneration in hippocampal neurons in every case; amyloid angiopathy present in 9 and mineralization of vessels in 10 cases; hyaline change in vessel walls and abundant lipofuscin in neurons and astrocytes were constant findings. No Lewy bodies were seen.

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PubMed1985

[Treatment of arterial hypertension in the aged subject with a converting enzyme inhibitor: enalapril].

The purpose of this study was to investigate the effectiveness and safety of enalapril in elderly people. A double-blind, randomized, placebo-controlled trial was carried out in 32 subjects aged from 75 to 97 years (mean: 86 years) with blood pressure values equal or superior to 160/90 mmHg. After 8 weeks of treatment with enalapril in doses of 20 to 40 mg/day, the systolic pressure was lowered from 190 +/- 16 to 151 +/- 19 mmHg (P less than 0.0001) and the diastolic pressure from 102 +/- 7 to 85 +/- 11 mmHg (P less than 0.0001). Systolic and diastolic pressures were also significantly reduced in subjects under placebo (from 183 +/- 16 to 165 +/- 21 mmHg, P less than 0.001; and from 101 +/- 9 to 91 +/- 13 mmHg, P less than 0.001, respectively), but the degree of reduction was significantly superior with enalapril (systolic: 39 +/- 25 vs 18 +/- 19 mmHg, P less than 0.005; diastolic: 17 +/- 13 vs 11 +/- 12, P less than 0.001); blood pressure was inferior to 160/90 mmHg in 67% of the subjects treated, as against 35% of those under placebo. Two patients under enalapril died: one on the 27th, the other on the 47th day of treatment. No relation could be established between these deaths and the drug, and this figure of 2 is not significantly different for the number of deaths expected over the same period in a population of that age-group. Among the patients under placebo, one had pulmonary embolism on the 34th day and another had a sudden increase in blood pressure on the 6th day, requiring discontinuation of treatment. It is concluded that enalapril administered alone is effective and well tolerated. Long-term studies are needed to find out whether this angiotensin-converting enzyme inhibitor is superior to a diuretic as initial treatment of arterial hypertension.

Acute Kidney Injury↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

[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.

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PubMed1983

[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.

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PubMed1982

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.

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PubMed1979

[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↗
PubMed1978

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.

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