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Risks and benefits in the trial of the European Working Party on High Blood Pressure in the Elderly
A Fletcher1, A Amery, W Birkenhäger
1Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Insights
This study found that treating hypertension in older adults with a combination diuretic and methyldopa prevented major cardiovascular events. However, active treatment increased risks of impaired renal function, hypokalemia, gout, and elevated uric acid levels.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases, particularly in individuals over 60 years of age.
- Effective antihypertensive therapy is crucial for reducing morbidity and mortality in this demographic.
- The study investigates the efficacy and safety of a specific combination therapy in elderly hypertensive patients.
Purpose of the Study:
- To evaluate the clinical benefits and adverse effects of a combined potassium-losing and potassium-sparing diuretic with methyldopa in hypertensive patients over 60.
- To determine the impact of this active treatment on fatal and non-fatal cardiovascular and cerebrovascular events.
- To identify and quantify specific adverse biochemical and clinical events associated with the active treatment regimen.
Main Methods:
- A double-blind, placebo-controlled trial was conducted involving hypertensive patients aged 60 years and older.
- The active group received a combination of triamterene (50 mg) and hydrochlorothiazide (25 mg), with the option to increase the dose and add methyldopa (up to 2 g daily).
- Adverse effects were assessed through biochemical monitoring, investigator reports, concomitant medication use, and patient symptom questionnaires.
Main Results:
- Active treatment prevented an estimated 11 fatal cardiac events, 6 fatal strokes, 11 non-fatal strokes, and 8 cases of severe congestive heart failure per 1000 patients treated for one year.
- Significant excess incidence rates (per 1000 person-years) were observed in the active group for impaired renal function (serum creatinine > 180 µmol/l), mild hypokalemia (serum potassium < 3.5 mmol/l), gout reports, and elevated serum uric acid.
- Elevated blood sugar and use of hypoglycemic drugs showed a trend towards being more frequent in the active group but did not reach statistical significance. Incidence of anemia, depression, and liver/gallbladder/pancreas diseases was low in both groups.
Conclusions:
- Combination therapy with triamterene, hydrochlorothiazide, and methyldopa is effective in preventing major adverse cardiovascular and cerebrovascular outcomes in hypertensive patients over 60.
- This treatment regimen is associated with an increased risk of impaired renal function, hypokalemia, gout, and hyperuricemia.
- The benefits of reduced cardiovascular events appear to outweigh the risks of these specific adverse effects, though careful monitoring is warranted.
Abstract:
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)