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April 23/30, 2003

Long-term Cardiovascular Consequences of Diuretics vs Calcium Channel Blockers vs Angiotensin-Converting Enzyme Inhibitors

JAMA. 2003;289(16):2066. doi:10.1001/jama.289.16.2067

To the Editor: During the course of the ALLHAT study,1 about 10% of all patients developed new diabetes, defined as a fasting blood sugar greater than 126 mg/dL. Interestingly, the risk among patients on chlorthalidone was between 43% to 65% higher vs those on lisinopril and between 18% to 30% higher vs those on amlodipine.

These findings corroborate previous findings of a moderate risk of diabetes with thiazide diuretics2,3 and of an equally moderate protective effect of drugs that block the renin-angiotensin system.4,5 However, the ALLHAT authors state, "Overall these metabolic differences did not translate into more cardiovascular events or into higher all-cause mortality in the chlorthalidone group compared with the other 2 groups." Although it may seem reassuring that none of the complications of diabetes was observed in ALLHAT, it must be remembered that antihypertensive therapy is lifelong, and that, therefore, a period of 2 to 6 years, such as in ALLHAT, is unlikely to estimate the long-term sequelae of the high risk of diabetes associated with chlorthalidone. Given that diabetes has reached epidemic proportions in industrialized countries, any factor that is known to accelerate this risk should be avoided, unless the benefits clearly outweigh the risks. Since in ALLHAT there was no difference in primary outcome nor in mortality between the 3 treatment arms, we suggest that thiazide diuretics should be avoided or at least not used as monotherapy for patients with hypertension at risk for diabetes.