New research shows that in people with high blood pressure as part of metabolic syndrome, a cluster of conditions that increases the risk for heart disease, diuretics offer greater protection against cardiovascular disease, including heart failure, and are at least as effective for lowering blood pressure as newer, more expensive medications.
The findings run counter to current medical practices that favor ACE-inhibitors, alpha-blockers, and calcium channel blockers for treatment of high blood pressure in those with metabolic syndrome. In addition, the results provide important new evidence supporting the use of diuretics for initial blood pressure-lowering therapy in black patients with metabolic syndrome.
The latest findings from the "Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial" or ALLHAT, sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, are published in the January 28 issue of Archives of Internal Medicine.
"These findings are particularly important for patients with metabolic syndrome because many doctors currently prescribe alpha-blockers, calcium channel blockers, and ACE-inhibitors due to their more favorable short-term effects on blood sugar and blood cholesterol levels. However, this new analysis shows that diuretics are better at preventing cardiovascular disease and thus does not support the selection of the newer drugs over diuretics for preventing poor health outcomes related to hypertension or for lowering high blood pressure," said Elizabeth G. Nabel, M.D., director, NHLBI.
ALLHAT is the largest study to compare a diuretic (chlorthalidone) with three newer classes of medications to treat high blood pressure: a calcium-channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), and an angiotensin-converting enzyme (ACE) inhibitor (lisinopril). Each drug was used to start treatment and other medications could be added if necessary to control blood pressure. The study originally reported in 2002 that diuretics were the most beneficial of the drug classes studied for treating high blood pressure and for protecting against adverse cardiovascular outcomes.
This latest analysis shows that even among men and women with metabolic syndrome, and for both black and non-black (Caucasians, Hispanics, Asians/Pacific Islanders and American/Alaskan Natives) participants, the less costly diuretics consistently control blood pressure, are equally beneficial in preventing heart attack and coronary heart disease death. They are also more beneficial than newer medications in preventing one or more other forms of cardiovascular disease including heart failure and stroke. Another ALLHAT paper, published online on November 13, and reported in the February 2008 issue of Diabetes Care, reached similar conclusions when patients with diabetes were excluded.
People with metabolic syndrome have three or more risk factors for heart disease including elevated blood pressure (130/85 mmHg or higher), low HDL (good cholesterol) levels (HDL less than 40 mg/dL in men or less than 50 mg/dL in women), and diabetes or pre-diabetes (fasting blood glucose of 100 mg/dL or greater).
The ALLHAT study was a randomized, double-blind trial involving 42,418 participants, ages 55 and older with high blood pressure (140/90 mm Hg or greater) and at least one other risk factor for heart disease. Of those, 23,077 had metabolic syndrome with diabetes or pre-diabetes (fasting blood glucose of 100 mg/dL or greater) at the time of enrollment. Roughly 35 percent of the participants were black.
In both black and non-black study participants with metabolic syndrome, the diuretic-based treatment was more protective against heart failure and also against overall cardiovascular disease (coronary heart disease, stroke, heart failure, or peripheral arterial disease combined) when compared with the ACE-inhibitor and alpha-blocker-based treatments. Compared with the calcium channel blocker-based treatment, the diuretic-based treatment was more protective against heart failure.
"The ALLHAT study has been remarkably consistent in showing that the lower-cost diuretic is superior to newer medications for the prevention of cardiovascular disease. The data show that diuretics can be effective as a single-drug treatment for high blood pressure and be included in multi-drug treatment regimens in most patients, including those with metabolic syndrome," said Paula Einhorn, M.D., program director, NHLBI Division of Prevention and Population Sciences.
When compared with those taking diuretics, black participants with metabolic syndrome receiving ACE-inhibitors had poorer blood pressure control and a 24 percent greater risk of overall cardiovascular disease. This included a 19 percent greater risk of coronary heart disease, a 37 percent greater risk of stroke, and a 49 percent greater risk of heart failure. They also had a 70 percent greater risk of kidney failure.
"In black patients with high blood pressure and metabolic syndrome, the evidence from ALLHAT overwhelmingly supports the choice of thiazide-type diuretics," said Jackson T. Wright, Jr., M.D., Ph.D., professor of medicine, Case Western Reserve University and the study's lead author.
"Medications to treat hypertension should always be combined with lifestyle approaches to lowering blood pressure. Patients should discuss these study results and their treatment with their doctors before making any changes," Einhorn added.
To arrange an interview about ALLHAT, please contact the NHLBI Communications Office at (301) 496-4236 or email [email protected]. To reach author Jackson Wright, please contact Alicia Reale in the media relations department at University Hospitals, or email at [email protected].
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics.