Biomedical subjects

F Forette

Publications and source records attributed to F Forette.

At least 37 records · Page 2Linked to original sources

PubMed1990

Age-related effects of placebo and active treatment in patients beyond the age of 60 years: the need for a proper control group.

The age-related response to placebo and active antihypertensive treatment was evaluated in 742 elderly hypertensive patients who were followed in the double-blind placebo-controlled trial conducted by the European Working Party on High blood pressure in the Elderly (EWPHE). In the two treatment groups, the fall in systolic and diastolic blood pressures after 3 months was negatively correlated with age (P less than 0.02), indicating that the hypotensive effect of placebo and active treatment was more pronounced in older patients. Further comparison of the two treatment groups failed to demonstrate any statistical differences in the slopes of the hypotensive effect on age. These conclusions were not altered by cumulative adjustments for baseline blood pressure, pulse rate, serum creatinine and the presence of cardiovascular complications at entry. In conclusion, in the present study, a similar blood-pressure-lowering action which increased with age was observed on active and placebo treatment; thus, proof that an observed age-related hypotensive effect is caused by a particular drug requires comparison with a control group on placebo.

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PubMed1990

[Value and limits of medical treatment of hypertension in the aged person].

Most of the therapeutic trials (VA Study, HDFP, Australian Therapeutic Trial, EWPHE Study, Coope's Study) are in favour of the benefit of antihypertensive treatment over the age of sixty. But, on the other hand, information is lacking on:--The effectiveness of treatment of isolated systolic hypertension;--The effectiveness of treatment in very old people, particularly over eighty;--The effectiveness of treatment in preventing conditions which were not included in the former trials such as vascular dementias. Two trials concerning elderly patients with systolic hypertension are in progress, the SHEP Study in the USA and the European study called Syst-Eur. It is expected that these trials will give answers allowing a more accurate management of this major risk factor for cardiovascular diseases in the Elderly.

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PubMed1989

Relation between mortality and treated blood pressure in elderly patients with hypertension: report of the European Working Party on High Blood Pressure in the Elderly.

OBJECTIVE: To investigate the relation between mortality and treated systolic and diastolic blood pressures. DESIGN: Randomised double blind placebo controlled trial. Mortality in the two treatment groups was examined in thirds of treated systolic and diastolic blood pressures. PATIENTS: 339 And 352 patients allocated to placebo and active treatment, respectively. The groups were similar at randomisation in sex ratio (70% women), mean age (71.5 years), blood pressure (182/101 mm Hg), and proportion of patients with cardiovascular complications (35%). MEASUREMENTS AND MAIN RESULTS: In the placebo group total mortality rose with increasing systolic pressure whereas it had a U shaped relation with diastolic pressure, the total lowest mortality being in patients in the middle third of the distribution of diastolic pressure. In the group given active treatment total mortality showed a U shaped relation with systolic pressure and an inverse association with treated diastolic pressure. In both groups cardiovascular and non-cardiovascular mortality followed the same trends as total mortality. The increased mortality in the lowest thirds of pressure was not associated with an increased proportion of patients with cardiovascular complications at randomisation or with a fall in diastolic pressure exceeding the median fall in pressure in each group. In contrast, patients in the lowest thirds of pressure showed greater decreases in body weight and haemoglobin concentration than those in the middle and upper thirds of pressure. CONCLUSIONS: In patients taking active treatment total mortality was increased in the lowest thirds of treated systolic and diastolic blood pressures. This increased mortality is not necessarily explained by an exaggerated reduction in pressure induced by drugs as for diastolic pressure a U shaped relation also existed during treatment with placebo. In addition, patients in the lowest thirds of systolic and diastolic pressures were characterised by decreases in body weight and haemoglobin concentration, and the patients in the lowest thirds of diastolic pressure taking active treatment also by an increased non-cardiovascular mortality, suggesting some deterioration of general health.

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PubMed1989

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

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PubMed1989

Nicardipine in elderly patients with hypertension: a review of experience in France.

A double-blind, placebo-controlled clinical trial in France has studied the efficacy and safety of nicardipine in 31 elderly patients, aged 57 to 95 years (mean age 84 years), 16 of whom were actively treated with nicardipine, 10 to 30 mg three times a day (mean dose 69.4 mg/day). After 4 weeks, nicardipine lowered mean blood pressure (186/99 to 150/83 mm Hg; p less than 0.001), and the changes in systolic and diastolic blood pressure were significantly greater in the nicardipine group than in the placebo group. Nicardipine was well tolerated; orthostatic hypotension was not observed and there was no change in heart rate. Plasma renin activity (PRA) was measured in eight patients, but there was no correlation between PRA and the antihypertensive effect of nicardipine. Results of a pharmacokinetic study performed in 15 elderly patients showed a rapid rate of absorption and higher plasma levels than those observed in younger patients with hypertension (mean age 54 years). The results support those of the major French multicenter open study of 29, 104 elderly patients with hypertension (mean age 64 +/- 12 years) treated with nicardipine. The findings of this trial are reviewed and discussed, and recommendations made on the directions for future research in cardiovascular medicine with calcium channel blockers. Results of the trials discussed in this article show that nicardipine is an effective and well-tolerated drug in elderly patients and has wide-ranging effects on the cardiovascular system.

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PubMed1989

Alzheimer's disease and THA: a review of the cholinergic theory and of preliminary results.

The cholinergic theory is based on the assumption that acetylcholine (ACh) metabolism plays an important role in memory processes and that the deterioration of memory and other cognitive functions in Alzheimer's disease (AD) is directly related to degeneration of cerebral presynaptic cholinergic neurons. This article reviews various therapeutic strategies based on this theory and particularly that of using cholinesterase inhibitors such as tetrahydroaminoacridine (THA). The few available studies--all preliminary--on THA are reviewed. They show that THA is neither a cure nor a definitive treatment for AD. However, the preliminary reports suggest for the most part a certain degree of efficacy, greater at any rate than the efficacy of other pharmaceutical agents tried so far. Despite the apparent multiplicity of pharmacological actions of THA, it appears that the cholinergic hypothesis remains valid and should be pursued further.

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PubMed1989

[Significance of inhibitors of conversion enzymes in elderly subjects. The example of perindopril].

The effectiveness and safety of perindopril in elderly hypertensive patients has clearly been demonstrated. In a randomized, double-blind drug versus placebo study involving 34 such patients of mean age 84 years, we observed a 10 p. 100 fall in systolic arterial pressure (p less than 0.01) and a 9 p. 100 fall in diastolic arterial pressure (p less than 0.01) in the perindopril group. The corresponding figures in the placebo group were 5 p. 100 and 4 p. 100 respectively, the difference between the two groups not being significant. The drug was well tolerated, both clinically and biochemically. However, a significant (p less than 0.01) increase in blood potassium level (albeit within normal limits) was observed in the treated group. An open trial conducted in 91 patients (mean age 79.1 years) followed up for 6 years confirmed the acceptability of the drug despite a transient decrease of creatinine clearance recorded in one patient. The effectiveness of perindopril, evaluated less unquestionably in this open trial, was excellent, the hypertension being controlled at the end of treatment in 92.5 p. 100 of the patients. In a trial performed on healthy volunteers, Reid found that perindopril had a greater effect of arterial pressure in elderly subjects, probably due in part to their high blood pressure and to an earlier and more prolonged inhibition of the angiotensin-converting enzyme (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

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.

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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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