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C Bulpitt

Publications and source records attributed to C Bulpitt.

At least 37 records · Page 2Linked to original sources

[SYST-EUR: a multicenter trial of treatment of systolic hypertension in aged subjects. An initial report].

Syst-Eur is a multicentre placebo-controlled outcome trial, designed by the European Working Party on High Blood Pressure in the Elderly (EWPHE), to investigate the effect of antihypertensive treatment on the incidence of stroke in elderly patients with isolated systolic hypertension (ISH). Eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic blood pressure less than 95 mmHg. The present paper in an interim report on the first 316 patients randomized into this trial. The placebo (N = 170) and active treatment (N = 146) groups were similar at randomization with respect to age (73 +/- 8 years; mean +/- standard deviation), sitting blood pressure (178 +/- 12/85 +/- 7 mmHg), percentage men (34%) and percentage of patients with cardiovascular complications (29%). After randomization blood pressure fell more (p < 0.001) on active treatment than in the placebo group (19 +/- 20/6 +/- 10 mmHg versus 7 +/- 19/1 +/- 10 mmHg for the sitting blood pressure). This first interim report on the Syst-Eur trial demonstrates that a multinational trial in elderly patients with ISH is feasible and that a significant blood pressure difference between the 2 treatment groups can be achieved and maintained. New centres are being recruited in order to randomize a total of 3,000 patients.

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Quality of life and antihypertensive drugs in the elderly.

Hypertension is common in the elderly with estimates of around 10-20% showing a sustained level of pressure, either systolic (greater than or equal to 160 mmHg), or diastolic (greater than or equal to 90 mmHg) or both. The benefits of treating subjects with raised diastolic pressure was shown by the trials of the European Working Party on High Blood Pressure in the Elderly (EWPHE), the Hypertension in Elderly Patients in Primary Care (HEP), and the Swedish Trial in Old patients with Hypertension (STOP-Hypertension). Evidence for the benefit of treating isolated systolic hypertension in the elderly was provided in one trial (SHEP: Systolic Hypertension in the Elderly Program), and the results of two others are awaited. However, it is important to provide data on all treatment effects, including adverse reactions as well as benefits. In addition to traditional measures of mortality, morbidity and side effects, the quality of life in patients on antihypertensive treatment should be considered. The methods of measuring quality of life in trials is discussed, and some results presented.

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Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly.

Hypertensive patients over the age of 60 years were admitted to a double-blind placebo-controlled trial. Patients in the actively treated group received a combined potassium-losing and -sparing diuretic (triamterene 50 mg plus hydrochlorothiazide 25 mg; n = 416); this dose could be doubled and methyldopa (up to 2 g, daily) was added in 35% of patients when blood pressure remained high. The placebo group (n = 424) received matching capsules and tablets. Adverse effects were assessed in the double-blind period of the trial by calculating the incidence of abnormal biochemical results, investigator reports of diseases and prescriptions of concomitant therapy and a self-administered symptom questionnaire completed by patients. In 1000 hypertensive subjects over 60 years of age, 1 year of active treatment would prevent 11 fatal cardiac events, 6 fatal and 11 non-fatal strokes and 8 cases of severe congestive heart failure. No unexpected adverse treatment effects were observed. A significant excess incidence rate (per 1000 person years) was found in the active group compared with placebo for: (1) impaired renal function, a serum creatinine greater than 180 mumol/l (2.0 mg/dl); (2) mild hypokalaemia, a serum potassium less than 3.5 mmol/l; (3) reports of gout; and (4) an elevated serum uric acid greater than 0.52 mmol/l in men or greater than 0.46 in women. Elevated blood sugar and prescriptions for hypoglycaemic drugs tended to be more frequent in the actively treated group, but this difference was not statistically significant. In both groups, there was a low incidence (less than 7 per 1000 person years) of anaemia and depression and diseases of the liver, gall bladder or pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

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[A comparison of the effects of verapamil and nifedipine on the quality of life].

Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 months randomized double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95 to 115 mm Hg was required for inclusion in the trial. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (p less than 0.01). The reporting of swollen ankles and flushing (p less than 0.05) increased on nifedipine, and nocturia (p less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (p = 0.05). There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (p less than 0.01). The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.

Adult↗

Is a high serum cholesterol level associated with longer survival in elderly hypertensives?

The relationship between serum total cholesterol, measured at randomization, and mortality was investigated in 822 patients, who were followed for an average of 3.1 years in a double-blind trial, conducted by the European Working Party on High Blood Pressure in the Elderly. Serum cholesterol, measured at randomization, was 0.54 mmol/l higher in women than in men, and declined with increasing age in both men (0.028 mmol/l per year) and women (0.036 mmol/l per year). During follow-up on randomized treatment, cholesterol fell by a similar amount with placebo (0.11 mmol/l per year) and with active treatment (0.14 mmol/l per year). Active treatment consisted of hydrochlorothiazide (25-50 mg/day) plus triamterene (50-100 mg/day) with the addition of alpha-methyldopa (0.5-2.0 g/day) in one-third of the patients. Serum total cholesterol, measured at randomization, was independently and inversely correlated with total (P = 0.03), non-cardiovascular (P = 0.03) and cancer (P = 0.04) mortality during follow-up on double-blind treatment. Total and non-cardiovascular mortality were also negatively correlated with haemoglobin and body weight at randomization.

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A comparison of verapamil and nifedipine on quality of life.

1. Aspects of quality of life (symptoms, psychological well-being and activity) were evaluated by self-administered questionnaires in a 4 month randomised double-blind trial of titrated doses of verapamil slow release (n = 41) compared with nifedipine retard (n = 40). An untreated diastolic blood pressure of 95-115 mm Hg was required for inclusion in the trial. 2. The mean age in both groups was 55 years. A significant difference between the two drugs was found in the average reporting of symptoms with an increase on nifedipine (P less than 0.01). The reporting of swollen ankles and flushing (P less than 0.05) increased on nifedipine, and nocturia (P less than 0.05) increased on verapamil. Measures of psychiatric morbidity tended to improve on verapamil and deteriorate on nifedipine. Only the change in cognitive function was significant between the drugs, being worse on nifedipine (P = 0.05). 3. There was no difference between the two groups in the fall in diastolic blood pressure (average 18 mm Hg on nifedipine and 17 mm Hg on verapamil). There was a significantly greater fall in systolic blood pressure on nifedipine (23 mm Hg) compared with verapamil (13 mm Hg) (P less than 0.01). 4. The two drugs differed in their effects on measures of quality of life. The improvements in symptomatic complaints and psychological well-being on verapamil may have been due to inclusion in a trial, although we cannot exclude the possibility of a drug effect. Conversely the increase in symptoms and self-assessed cognitive impairment on nifedipine were considered to be side-effects of the drug.

Adult↗

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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Quality of life on angina therapy: a randomised controlled trial of transdermal glyceryl trinitrate against placebo.

In a randomised controlled trial in 427 men with chronic stable angina continuous use of 5 mg transdermal glyceryl trinitrate (GTN) showed no advantage over placebo in terms of efficacy (anginal attack rates and sublingual GTN consumption) or quality of life (as measured with the sickness impact profile and a health index of disability). Patients on the active drug reported headaches more frequently than patients on placebo, and a higher proportion of them withdrew from the trial because of headache. Quality-of-life measurements showed a significant adverse effect of active treatment, principally in the social interaction dimension of the sickness impact profile. A similar effect was observed in placebo patients when crossed to active treatment in a 4-week single-blind period. The results suggest no benefit in the relief of chest pain from 5 mg transdermal GTN when used continuously.

Administration, Cutaneous↗

Beta adrenoceptor blockade is associated with increased survival in male but not female hypertensive patients: a report from the DHSS Hypertension Care Computing Project (DHCCP).

The DHCCP is a multicentre observational study of patients being treated for hypertension in the United Kingdom. The influence of the type of anti-hypertensive therapy on survival was examined in 2,697 patients followed from 1971 with 206 deaths up to November 1981. Patients were classified by three types of treatment after one year in the project: betablockers (1,387), methyldopa (452) and others (667), (70% on diuretics only). The data were analysed both for all patients and for a subset excluding patients with previous ischaemic heart disease by all cause and IHD age-adjusted rates and life table analysis. Men on beta blockers had lower rates for total mortality, when compared with men on methyldopa (64% of the methyldopa rate, P less than 0.05) and when compared with men on other treatments (76% of the other treatment rate, P less than 0.1). The results for IHD mortality were similar. This improved survival of men in the beta blocker group was also found in the subset with no prior history of IHD. The benefit of beta blockers was not apparent in women: the lowest rates were observed for women on methyldopa, but the confidence limits for the ratios of relative rates were wide. Adjustment for blood pressure and cigarette smoking using the Cox proportional hazards model did not substantially modify the ratios of the mortality rates for the treatment groups. A sub-group analysis showed the reduction in all cause and IHD mortality associated with beta blockers was mainly due to the effect in non-smoking men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Diuretics--a risk in the long-term treatment of hypertensive patients?

The trial of the European Working Party on High blood pressure in the Elderly (EWPHE) revealed an overall decrease in cardiovascular mortality and morbidity in the actively treated patients. They received as first-line drugs a combination of hydrochlorothiazide and triamterene; methyldopa was added as necessary. The present post hoc analysis examined the effect of the diuretic treatment on cardiovascular events, both when given alone and in conjunction with methyldopa, by calculating the relative hazard rates (RHR) for cardiovascular mortality and morbidity. Using the Cox proportional hazard model, compared with placebo, a 34% reduction in cardiovascular mortality in the intention-to-treat analysis was demonstrated in the diuretic (hydrochlorothiazide and triamterene) group with an RHR of 0.66 and a 95% confidence interval (CI) of 0.44-0.97; the 16% decrease in the group treated with diuretics and methyldopa was not significant (RHR, 0.84; 95% CI, 0.56-1.25). The effect of treatment in the latter combined group became significant (RHR, 0.62; 95% CI, 0.40-0.95) when all cardiovascular study terminating events were considered; they were reduced by 38%. No effect of treatment on mortality from all causes was detected.

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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↗

The effect of the contraceptive pill on blood pressure: a randomized controlled trial of three progestogen-oestrogen combinations in Szeged, Hungary.

As part of an international multicentered investigation a double-blind comparative clinical trial was conducted at the Department of Obstetrics and Gynecology, University Medical School, Szeged, Hungary, in order to study the effect of different combined oral contraceptives on blood pressure. Healthy, normotensive women were randomly allocated to either of the following oral contraceptives: 250 micrograms levonorgestrel + 50 micrograms ethinyloestradiol (LN 250 + EE 50), 250 micrograms levonorgestrel + 30 micrograms ethinyloestradiol (LN 250 + EE 30), 1 mg norethisterone acetate + 50 micrograms ethinyloestradiol (NA 1 + EE 50). Standardized blood pressure measurements were carried out at admission and 3, 6, 9, and 12 months after admission. Blood pressure change from admission to subsequent visits was analysed in subjects who were seen by the same observer both at admission and the follow-up under consideration. The systolic blood pressure slightly but not significantly increased in groups LN 250 + EE 50 and NA 1 + EE 50, whereas the diastolic pressure showed a minimal decrease. In group LN 250 + EE 30 both systolic and diastolic blood pressure increased significantly (+5.58 and +3.20 mm Hg, respectively) at the 12-month follow-up. The study supports previous findings that combined oral contraceptive use is associated with a moderate rise in blood pressure. The progestogen-to-oestrogen ratio in the pill may be as important in this context as the dose of either component itself.

Adolescent↗

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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Influence of antihypertensive drug treatment on morbidity and mortality in patients over the age of 60 years. European Working Party on High blood pressure in the Elderly (EWPHE) results: sub-group analysis on entry stratification.

The European Working Party on High blood pressure in the Elderly (EWPHE) trial was a double-blind randomized placebo-controlled trial of antihypertensive treatment in patients over the age of 60 years. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range of 90-119 mmHg and a systolic blood pressure in the range of 160-239 mmHg. Eight-hundred and forty patients were randomly assigned either to active treatment (hydrochlorothiazide + triamterene) or a matching placebo. If blood pressure remained elevated methyldopa was added to the active regimen and matching placebo to the placebo regimen. Before randomization, the patients were stratified in eight strata according to sex, age groups between 60 and 69 years or 70 years and over, and the presence or absence of cardiovascular complications of hypertension. Both the intention-to-treat and 'on randomized treatment' analyses suggested a benefit from active treatment in men and women. Formal statistical significance was achieved for male cardiovascular mortality (intention-to-treat analyses) and for cardiovascular events in females. Although the event rates were greater for patients with previous cardiovascular events and patients over the age of 70 years, the percentage reduction in cardiovascular events was similar in these groups to those without complications and in patients between 60 and 69 years of age. However, little benefit from treatment could be demonstrated in patients over the age of 80 years. The presence or absence of smoking had no influence on response to treatment in these elderly patients.

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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↗

Influence of hypotensive drug treatment in elderly hypertensives: study terminating events in the trial of the European Working Party on High Blood Pressure in the Elderly.

The European Working Party on High Blood Pressure in the Elderly (EWPHE) trial was a double-blind randomized placebo-controlled trial of antihypertensive treatment in patients over the age of 60 years. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mmHg and a systolic blood pressure in the range of 160-239 mmHg. The patients (n = 840) were randomized either to active treatment (hydrochlorothiazide + triamterene) or matching placebo. If the blood pressure remained elevated, 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 of cardiovascular mortality rate (-27%, P = 0.037). The latter was due to a reduction of cardiac mortality (-38%, P = 0.036) and to a non-significant decrease of 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), due to a reduction of cardiac deaths (-47%, P = 0.048) and to a non-significant decrease of 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). In the patients randomized to active treatment there were 14 fewer cardiovascular deaths per 1000 patient-years during the double-blind part of the trial. Version 3.

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