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 <3.5 mmol/L) treated with low-dose chlorthalidone at 25 mg/d. The Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation (ALPINE) study3 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 trials4-7 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
Houston MC. ALLHAT Debate: Diuretics Are Not Preferred, First-Line Initial Therapy for Hypertension. Arch Intern Med. 2004;164(5):570–571. doi:10.1001/archinte.164.5.570-b
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