Choice of Antihypertensive Agents for Patients with Metabolic Syndrome: ALLHAT Results

Diuretics should continue to be first-line agents for treating patients with hypertension.
Results from the largest antihypertensive trial to date — ALLHAT — suggested that diuretics should be the preferred initial drug for treating patients with hypertension. However, concern persists about thiazides because of their adverse effects on insulin sensitivity and onset of diabetes, particularly among people with diabetes risk factors. In a post hoc analysis, ALLHAT researchers assessed metabolic and cardiovascular outcomes in nondiabetic patients with or without metabolic syndrome who were assigned to a diuretic (chlorthalidone), a calcium-channel blocker (CCB; amlodipine), or an angiotensin-converting–enzyme (ACE) inhibitor (lisinopril).
Among people with metabolic syndrome, diabetes incidence at 4 years was 17% in the chlorthalidone group, 16% in the amlodipine group, and 13% in the lisinopril group. Among people without metabolic syndrome, diabetes incidence was 7.7% in the chlorthalidone group, 4.2% in the amlodipine group, and 4.7% in the lisinopril group. However, risks for coronary heart disease, all-cause mortality, stroke, and end-stage renal disease were not significantly different among treatment arms (regardless of metabolic syndrome status). The incidences of heart failure and combined cardiovascular diseases were significantly lower in patients with metabolic syndrome who were assigned to chlorthalidone than among similar patients who received lisinopril.
Comment: Treatment with a diuretic, compared with a CCB or an ACE inhibitor, resulted in a higher incidence of diabetes among ALLHAT participants with or without metabolic syndrome. Nevertheless, the chlorthalidone group had clinical outcomes that were similar to (and, in some cases, better than) outcomes in the other groups, regardless of metabolic syndrome status. Given the relatively short duration of follow-up, the possibility that adverse events will accrue later cannot be excluded. However, as pointed out by the authors, long-term follow-up (14 years) in the Systolic Hypertension in the Elderly Program did not show excess risk for CVD mortality among participants who were assigned to a thiazide and who later developed diabetes (Am J Cardiol 2005; 95:29). Thiazides should remain a first-line agent for most patients and, at a minimum, should be a component of any multidrug regimen.
— Jamaluddin Moloo, MD, MPH
Published in Journal Watch General Medicine March 11, 2008
Citation(s):
Black HR et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care 2008 Feb; 31:353.