title: Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program.
abstract: The treatment of hypertension with high-dose thiazide diuretics results in potassium depletion and a limited benefit for preventing coronary events. The clinical relevance of hypokalemia associated with low-dose diuretics has not been assessed. To determine whether hypokalemia that occurs with low-dose 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 trial of chlorthalidone-based treatment of isolated systolic hypertension in older persons. After 1 year of treatment, 7.2% of the participants randomized 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 after the first annual visit, 451 participants experienced a cardiovascular event, 215 experienced a coronary event, 177 experienced stroke, and 323 died. After adjustment for known risk factors and study drug dose, the participants who received active treatment and who experienced hypokalemia had a similar risk of cardiovascular events, coronary events, and stroke as those randomized to placebo. Within the active treatment group, the risk of these events was 51%, 55%, and 72% lower, respectively, among those who had normal 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 events achieved among those who did not have hypokalemia.
authors.affiliation: Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: L V
authors.initials: LV
authors.lastname: Franse
authors.forename: M
authors.initials: M
authors.lastname: Pahor
authors.forename: M
authors.initials: M
authors.lastname: Di Bari
authors.forename: G W
authors.initials: GW
authors.lastname: Somes
authors.forename: W C
authors.initials: WC
authors.lastname: Cushman
authors.forename: W B
authors.initials: WB
authors.lastname: Applegate
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects*; D002752:Chlorthalidone / Q000008:administration & dosage* / Q000009:adverse effects*; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007008:Hypokalemia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D002752:Chlorthalidone