Patients with Metabolic Disorder show comparable or better results in Treatment of Hypertension with Diuretics

Diuretics appear to show similar or better results for treating hypertension in patients with metabolic syndromes, when compared with calcium-channel blockers, alpha-blockers, or angiotensin-converting enzyme (ACE) inhibitors. In a report in the January 28 issue of Archives of Internal Medicine, a JAMA/Archives journal, the latter appeared to offer no advantage in improving the clinical outcome. When compared across racial groups, this seemed to be especially true for black patients.

Metabolic syndrome (a set of medical disorders that contribute to cardiovascular disease and diabetes), coupled with hypertension (high blood pressure) can put patients at an especially high risk of complications from cardiovascular disease. In this study, metabolic syndrome was defined by hypertension combined with at least two of the following factors: diabetes or pre-diabetes; a body mass index (BMI) of at least 30; high triglyceride levels; or low levels of high-density lipoprotein ("good" cholesterol).

Some medications for high blood pressure, including alpha-blockers, ACE inhibitors, and calcium-channel blockers, have been advocated over other drugs, such as beta-blockers and diuretics, for their favorable short term effects on metabolic parameters such as blood glucose or blood cholesterol levels.

Jackson T. Wright Jr., M.D., Ph.D., of Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, and colleagues evaluated data collected in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). This study engaged a total 42,418 participants with hypertension and at least one other risk factor for cardiovascular disease. In this trial, patients were randomly assigned to take one drug as follows: diuretic (chlorthalidone, 15,255 patients), a calcium channel blocker (amlodipine besylate, 9,048 patients), an alpha-blocker (doxazosin mesylate, 9,061 patients) or an ACE inhibitor (lisinopril, 9,054 patients). This drug was used to start treatment, and if necessary for blood pressure control, other drugs could be added. Followup of participants continued for an average of 4.9 years for all drugs, with the exception of the alpha-blocker. The latter was discontinued after an average of 3.2 years due to increased rate of cardiovascular disease including an almost two-fold increased rate of heart failure in comparison to the diuretic population. Of the ALLHAT population, 23,077 ALLHAT participants (54.4 percent) met criteria for metabolic syndrome.

In their analysis, the authors report that, "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 [heart attack] and fatal coronary heart disease)." In patients displaying metabolic syndrome (7,327 black and 15,750 white patients), the calcium channel blocker, ACE inhibitor and alpha-blocker showed higher rates of heart failure compared with the diuretic; the ACE inhibitor and the alpha-blocker additionally carried an increased risk for combined cardiovascular disease.

"The lack of benefit of the agents with the most favorable metabolic profile (i.e., ACE inhibitors and alpha-blockers) was especially marked in the black participants with metabolic syndrome," the authors continue. "The magnitude of the excess risk of end-stage renal [kidney] 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 ACE 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 vs. the diuretic."

The authors conclude, "These findings fail to provide support for the selection of alpha-blockers, ACE 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."

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