The cardiotoxicity of thiazide diuretics: review of the evidence.
Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents.
Freis
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Veterans Administration Medical Center, Washington DC 20422.
D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001581:Benzothiadiazines; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000139:chemically induced*; D003645:Death, Sudden / Q000209:etiology; D004232:Diuretics; D015716:Electrocardiography, Ambulatory; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008274:Magnesium / Q000378:metabolism; D009203:Myocardial Infarction / Q000139:chemically induced; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D001581:Benzothiadiazines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D002784:Cholesterol; D008274:Magnesium