Hypokalemia associated with diuretic use and cardiovascular events in the systolic hypertension in the elderly program

The treatment of hypertension with high-dose thiazide diuretics results in potassium depletion and a limited benefit for preventing coronary events. T he clinical relevance of hypokalemia associated with low-dose diuretics has not been assessed. To determine whether hypokalemia that occurs with low-d ose diuretics is associated with a reduced benefit on cardiovascular events , we analyzed data of 4126 participants in the Systolic Hypertension in the Elderly Program (SHEP), a 5-year randomized, placebo-controlled clinical t rial of chlorthalidone-based treatment of isolated systolic hypertension in older persons. After 1 year of treatment, 7.2% of the participants randomi zed to active treatment had a serum potassium <3.5 mmol/L compared with 1% of the participants randomized to placebo (P<0.001). During the 4 years aft er the first annual visit, 451 participants experienced a cardiovascular ev ent, 215 experienced a coronary event, 177 experienced stroke, and 323 died . After adjustment for known risk factors and study drug dose, the particip ants who received active treatment and who experienced hypokalemia had a si milar risk of cardiovascular events, coronary events, and stroke as those r andomized to placebo. Within the active treatment group, the risk of these events was 51%, 55%, and 72% lower, respectively, among those who had norma l serum potassium levels compared with those who experienced hypokalemia (P <0.05), The participants who had hypokalemia after 1 year of treatment with a low-dose diuretic did not experience the reduction in cardiovascular eve nts achieved among those who did not have hypokalemia.