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.

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.

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.

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.

The progress of patients in the European Working Party on Hypertension in the Elderly trial.

792 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). Half were treated with hydrochlorothiazide and triamterene and half were given placebo and a second capsule was given and if necessary up to 2 g of methyldopa/day. The measurements in a sample of 157 patients suggested 80-86% compliance rate. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during five years of follow-up. The increase in serum creatinine found in the actively treated group was related to the decrease in sitting systolic blood pressure. Changes in serum uric acid correlated with changes in serum creatinine both in the placebo and in the actively treated group. Fasting blood glucose changed significantly in the active treatment group. The balance between this decreased risk on the basis of the blood pressure reduction and the increase produced by the rise in blood glucose and the other treatment effects remains to be determined. The trial continues and more patients are being admitted.

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.

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.