(Hypertension. 2000;35:1025.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Hypokalemia Associated With Diuretic Use and Cardiovascular Events in the Systolic Hypertension in the Elderly Program
From the Institute for Research in Extramural Medicine, Vrije Universiteit (L.V.F.), Amsterdam, The Netherlands; Sticht Center on Aging, Department of Internal Medicine, Wake Forest University Baptist Medical Center (M.P.), Winston Salem, NC; Department of Gerontology and Geriatrics, University of Florence and ‘Careggi’ Hospital (M.D.B.), Florence, Italy; Department of Preventive Medicine, University of Tennessee (G.W.S., W.C.C.), Memphis, Tenn; Veterans Affairs Medical Center (W.C.C.), Memphis, Tenn; and the Department of Internal Medicine, Wake Forest University School of Medicine (W.B.A.), Winston Salem, NC.
Correspondence to Marco Pahor, MD, Sticht Center on Aging, Department of Internal Medicine, Wake Forest University Baptist Medical Center, Medical Center Blvd, Winston Salem, NC 27157. E-mail mpahor{at}wfubmc.edu
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.
Key Words: hypokalemia • diuretics • myocardial infarction • stroke • clinical trials
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