Diuretics appear to be equal to or better than calcium-channel blockers, alpha-blockers, and angiotensin-converting enzyme inhibitors for treating hypertension in patients with metabolic syndrome, according to an article in the January 28 issue of Archives of Internal Medicine.

Metabolic syndrome was defined as hypertension plus at least two of the following factors: diabetes or pre-diabetes; a body mass index of at least 30; high triglyceride levels; or low levels of high-density lipoprotein cholesterol. Because some medications for hypertension have a favorable metabolic profile-for instance, more favorable short-term effects on blood glucose or blood cholesterol levels-they have been advocated over other drugs (namely, beta-blockers and diuretics) for treatment of patients with metabolic syndrome.

Jackson T. Wright Jr., MD, PhD, of Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, and colleagues analyzed data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

A total of 42,418 participants with hypertension and at least one other risk factor for cardiovascular disease were randomly assigned to take a diuretic (chlorthalidone, 15,255 patients), a calcium-channel blocker (amlodipine besylate, 9,048 patients), an alpha-blocker (doxazosin mesylate, 9,061 patients) or an angiotensin-converting enzyme inhibitor (lisinopril, 9,054 patients).

Each drug was used to start treatment and other drugs were added if necessary. Patients were followed for an average of 4.9 years for all drugs except the alpha-blocker; that arm of the trial was discontinued after an average 3.2 years of follow-up in light of increased rates of cardiovascular disease, including a near two-fold increased rate of heart failure when compared with the diuretic arm. A total of 23,077 ALLHAT participants (54.4 percent) met criteria for metabolic syndrome.

"No differences were noted among the four treatment groups, regardless of race or metabolic syndrome status for the primary end point (non-fatal myocardial infarction and fatal coronary heart disease)," the authors wrote.

Among patients with metabolic syndrome (7,327 black and 15,750 white patients), the calcium channel blocker, angiotensin-converting enzyme inhibitor and alpha-blocker had higher rates of heart failure compared with the diuretic; the angiotensin-converting enzyme inhibitor and the alpha-blocker also had an increased risk of combined cardiovascular disease.

"The magnitude of the excess risk of end-stage renal disease (70 percent), heart failure (49 percent) and stroke (37 percent) and the increased risk of combined cardiovascular disease and combined coronary heart disease strongly argue against the preference of angiotensin-converting enzyme inhibitors over diuretics as the initial therapy in black patients with metabolic syndrome. Similar higher risk was noted for those randomized to the alpha-blocker versus the diuretic."

"These findings fail to provide support for the selection of alpha-blockers, angiotensin-converting enzyme inhibitors, or calcium channel blockers over thiazide-type diuretics to prevent cardiovascular or renal outcomes in patients with metabolic syndrome, despite their more favorable metabolic profiles," the authors concluded.