Antihypertensive Therapy-Associated Hypokalemia and Hyperkalemia

Abstract

See related article, pp 926–933 Hydrochlorothiazide was introduced into clinical practice in 1957 and chlorthalidone shortly thereafter. Diuretics continue to be a mainstay of antihypertensive therapy. They effectively reduce blood pressure and decrease hypertension-related morbidity and mortality. In addition, they are relatively inexpensive. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends diuretics as first-line therapy for the treatment of hypertension. The Antihypertensive and Lipid-Lowering Treatment to Preventing Heart Attach Trial (ALLHAT) was a prospective, randomized trial designed to compare the effects of diuretics with other antihypertensive agents on the incidence of coronary heart disease (CHD) and other cardiovascular disease (CVD) events. Beginning in 1994, 42000 participants aged ≥55 years with hypertension and ≥1 other CHD risk factor were randomized to receive initial therapy with chlorthalidone, lisinopril, amlodipine, or doxazosin.1 The doxazosin arm was terminated early because of a higher incidence of cardiovascular events, particularly congestive heart failure. During a mean follow-up of 4.9 years, there was no difference among the other 3 drug regimens in the primary outcome of combined fatal CHD or nonfatal myocardial infarction. Secondary outcomes were similar, except for higher rates of heart failure with amlodipine and higher rates of combined CVD, stroke, and heart failure with lisinopril compared with chlorthalidone. A decade ago, the ALLHAT investigators concluded that, “thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.” In response to concerns that low and high serum …