Non-potassium-sparing diuretics and risk of sudden cardiac death

Objective: To review current evidence for a possible association between the use of non-potassium-sparing diuretics and the risk of sudden cardiac death in hypertension. Methods: Examination of published randomized trials and recent case-control studies. Results: Numerous studies have shown that the administration of non-potassiumsparing diuretics causes a dose-dependent decrease in serum potassium levels in hypertensive patients. Although largely circumstantial, some evidence implies that diuretic-induced electrolyte depletion leading to arrhythmias may be the mechanism involved in the association between diuretics and sudden death. Published randomized trials on the efficacy of non-potassium-sparing diuretic therapy have consistently failed to show a reduction in the incidence of sudden cardiac death, while findings from hypertension trials including potassium-sparing diuretic combinations demonstrated an impressive decrease in coronary events. Two similar, recent case-control studies, together comprising 371 cases of sudden cardiac death in patients taking drug treatment for hypertension, indicated that hypertensive patients who were prescribed non-potassium-sparing diuretics had approximately double the risk of sudden cardiac death compared with users of potassium-sparing diuretic therapy. Although treatment allocation in these studies is, by definition, non-random, adequate measures were taken to reduce sources of bias. Conclusions: Current evidence supports the hypothesis that diuretic-induced potassium loss causes sudden cardiac death in some hypertensive patients. It seems prudent to use thiazide diuretics at a low dose only. Adding a potassium-sparing diuretic drug may further reduce the mortality risk.