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-potassium-sparing 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.
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.
D E
DE
Grobbee
A W
AW
Hoes
D001581:Benzothiadiazines; D002986:Clinical Trials as Topic; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004232:Diuretics; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D012307:Risk Factors; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects*
D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D011188:Potassium