Do non-potassium-sparing diuretics increase the risk of sudden cardiac death in hypertensive patients? Recent evidence.

Whether non-potassium-sparing diuretics (NPSD) increase the risk of sudden cardiac death in hypertensive patients has been vigorously debated. Diuretic-induced potassium or magnesium depletion leading to cardiac arrhythmias has been suggested as the underlying mechanism. A clear dose-response relationship between NPSD and the reduction in serum K+ exists. Data regarding serum Mg++ and intracellular K+ and Mg++ are too limited to allow conclusions. NPSD seem to increase the risk of ventricular arrhythmias among hypertensive patients with clinical evidence of heart disease, but the number of studies is small. The findings among patients without evidence of heart disease are less conclusive. The interpretation of the studies on electrolyte changes and arrhythmias following diuretic therapy is obscured by the fact that only a minority of studies included a randomly allocated placebo-treated control group. The large hypertension trials provide the strongest evidence that NPSD for hypertension may induce sudden death. Although blood pressure lowering may be expected to reduce the incidence of sudden cardiac death, the incidence in the NPSD group is similar to or even higher than that in the control group in 9 of 10 trials. We conclude that the beneficial effect of NPSD therapy for hypertension is partly offset by an excess risk of sudden death. Thus, alternative drugs, notably potassium-sparing diuretics or beta-blockers, could be preferred as antihypertensive drugs of first choice, although the efficacy of beta-blockers in older patients has recently been challenged.