ALLHAT Debate: Diuretics Are Not Preferred, First-Line Initial Therapy for Hypertension

Abstract

In a recent Commentary in the ARCHIVES, Dr Moser¹ has erroneously concluded that thiazide diuretics are the "gold standard" of hypertensive therapy and that they do not cause "metabolic abnormalities" such as dyslipidemia, hyperglycemia, new-onset diabetes, hypokalemia, or renal insufficiency. His conclusions are based on inherent design flaws and subsequent inaccurate data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), as well as a selected bias toward older studies, while ignoring recent clinical trials and even the reported diuretic-induced metabolic issues from ALLHAT. The Systolic Hypertension in the Elderly Program (SHEP) study² found no reduction in any cardiovascular events at 1 year in the 7.2% of subjects with hypokalemia (serum potassium level 3 confirms the metabolic dysfunction induced by thiazide diuretics alone or in combination with a β-blocker. The diuretic–β-blocker combination therapy compared with a calcium channel blocker–angtiotensin receptor blocker combination therapy resulted in a significantly greater incidence of insulin resistance, hyperglycemia, new-onset diabetes mellitus, dyslipidemia, metabolic syndrome, hypokalemia, hyperuricemia, and increased serum creatinine level at 1 year in a group of previously untreated hypertensive subjects.³ Other prospective clinical trials^4-7 and epidemiological studies⁸ have demonstrated more hyperglycemia and new-onset diabetes mellitus with use of diuretics⁴ and β-blockers⁵ compared with angiotensin-converting enzyme inhibitor,^4,6 angiotensin receptor blocker,⁵ or calcium channel blocker⁴ use, as well as more renal insufficiency.^7-9 Finally, thiazide diuretics increase homocysteine levels (≥16%), which may blunt their cardiovascular protection in coronary heart disease and stroke symdrome.⁹