The efficacy and safety of diuretics in treating hypertension.

The efficacy of thiazides and related diuretics in preventing most of the complications of hypertension has been conclusively documented in long-term controlled trials. Among their adverse effects, thiazides may induce a short-term increase in serum cholesterol levels. However, the elevation returns to pretreatment levels during long-term therapy. In addition, long-term treatment with thiazides is not associated with an elevation of blood glucose levels or an increased incidence of diabetes. Because the long-term controlled trials have shown that thiazides provide more protection against stroke than against coronary heart disease events, it is possible that the difference may be caused by adverse effects of the diuretics. In three of four recent trials that used low doses of thiazides plus potassium-sparing diuretics, the number of sudden deaths was reduced more than in other trials that used high doses of diuretics alone. A recent case-control study also found that small doses of diuretics combined with potassium-sparing drugs were associated with a reduced number of sudden deaths compared with high doses used alone. Although these results suggest that small doses reduce the risk for sudden death more than do large doses, they cannot be regarded as conclusive. A randomized double-blind trial comparing low and high doses of thiazide diuretics and potassium-sparing drugs must be done. For now, however, small doses seem prudent for treating hypertension.