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Thiazides first-choice antihypertensive even for patients with metabolic syndrome
New findings from ALLHAT fail to support the preference for calcium blockers, alpha blockers, or ACE inhibitors compared with thiazide diuretics in patients with metabolic syndrome, despite their more favorable metabolic profiles [1]. Indeed, the lack of benefit of the agents with the most favorable metabolic profile (ACE inhibitors and alpha blockers) was especially marked in the black participants with metabolic syndrome.
The analysis of ALLHAT patients by metabolic-syndrome status and by race, published in the January 28, 2008 issue of the Archives of Internal Medicine, was conducted by a group led by Dr Jackson Wright (General Clinical Research Center, Cleveland, OH). Results show the same outcome as the main trial—no benefit in terms of cardiovascular-event reduction (and increases in some end points) with the calcium blocker amlodipine, the alpha blocker doxazosin, or the ACE inhibitor lisinopril as compared with the thiazide diuretic chlorthalidone.
Metabolic benefits not translating into reduced events
Senior author of the paper, Dr Barry Davis (The University of Texas Health Science Center at Houston), commented to heartwire: "Even in patients with metabolic syndrome who have a whole spectrum of metabolic risk factors, these newer antihypertensives, with metabolic benefits compared with thiazide diuretics, were no better at reducing events than the diuretic. Therefore, the metabolic benefits of these newer agents are not being translated into a reduction in clinical outcomes." He added: "The two subgroups in which you might expect the most benefit from these newer agents are diabetics and the patients with metabolic syndrome. We have previously published the results in diabetics from ALLHAT, which also showed no benefit, and now we show the same thing in metabolic-syndrome patients."
The ALLHAT trial enrolled 42 418 men and women 55 years or older with hypertension and at least one additional risk factor for CHD who were randomized to therapy with chlorthalidone, amlodipine, lisinopril, or doxazosin. The doxazosin arm was stopped early because of a higher rate of cardiovascular events. The main results of the trial, reported in 2002, showed very similar rates of fatal CHD/nonfatal MI, the primary end point, with the other three agents, but better results in terms of secondary outcomes with the diuretic. Of note, the ACE inhibitor was significantly less effective in preventing several cardiovascular outcomes, particularly in black participants.
In the current paper, Wright et al note that half the ALLHAT patients met the definition for metabolic syndrome, and the results in this subgroup were very similar results to the main trial. While there were no differences among the four treatment groups for the primary end point, all three of the newer hypertensives showed significantly higher rates of heart failure compared with chlorthalidone in metabolic-syndrome patients, which were particularly marked for black patients.