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

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 2g, 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 @er 1000 person years) was found in the active group compared with placebo for: (1) impaired renal function, a serum creatinine > 180 pmolll (2.0 mgldl); (2) mild hypokalaemia, a serum potassium < 3.5 rnmolll; (3) reports of gout; and (4) an elevated serum uric acid >0.52 mmolll in men or >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 ( < 7 per 1000 person years) of anaemia and depression and diseases of the liver, gall bladder or pancreas. More patients reported a dr, mouth, blocked nose and diarrhoea in the active treatment group compared with placebo (P < 0.05). Dry mouth and diarrhoea were associated with methyldopa rather than diuretic. We conclude that the adverse effects do not outweigh the benefits of treatment in preventing stroke events, cardiac deaths and heart failure.Journal of Hypertension 1991, 9225-230

Management of hypertension in the elderly: attitudes of general practitioners and hospital physicians.

“…A number of other reasons may account for the reluctance of doctors to treat elderly patients with hypertension such as concerns about poor compliance, side-effects and adverse effects of lowering blood pressure excessively [16][17]. These issues remain unexplored with respect to hypertension.…”

The conundrum of hyperuricemia, metabolic syndrome, and renal disease

“…However, it has been reported that diuretic usage did not slow but rather accelerates renal progression in hypertensive patients despite reducing blood pressure. For example, the EWPHE [19], SHEP [20], INSIGHT [21], and ALLHAT [17] studies all reported that the usage of diuretics was statistically associated with a greater decline in renal function compared with the other treatment groups. Thus, while diuretics reduce blood pressure and blood pressureassociated events such as stroke and heart failure, they may be less effective at slowing renal disease or reducing cardiovascular events.…”

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

“…Even though there is an abundance of evidence supporting the beneficial effects of thiazide diuretics on cardiovascular outcomes, these agents may accelerate the onset of T2DM in patients with hypertension (particularly when used in high doses) [77,[87][88][89][90][91][92][93], although older studies often had method limitations [93]. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attacks Trial (ALLHAT) [70], the odds ratio of developing of developing T2DM at 2 years was significantly lower for lisinopril and amlodipine (0.55, P < .…”

“…Thiazide diuretics worsen glycemic control in a dose-dependent fashion by decreasing insulin secretion and peripheral insulin sensitivity [77,[87][88][89]97]. Hypokalemia (and perhaps hypomagnesemia) may play an important role in thiazide-induced glucose intolerance [77,[97][98][99], and deterioration in glucose metabolism occurs even with minimal decreases in serum potassium levels [90].…”