Barry R. Davis, M.D., Ph.D.
Director and Principal Investigator
ALLHAT Clinical Trials Center
Professor of Biometry
University of Texas School of Public Health, Houston
December 17, 2002
Press Conference Remarks
Release of the Results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: Background, Purpose, Study Design
Thank you, Dr. Lenfant.
Treatment for high blood pressure and high blood cholesterol includes lifestyle changes, such as increasing the amount of physical activity, losing weight, following an eating plan that is low in saturated fat and cholesterol, limiting salt intake, and not smoking. If these changes alone cannot lower elevated blood pressure or cholesterol enough, then medications are added to the treatment.
ALLHAT was designed to compare the effectiveness of different high blood pressure drugs and, in a separate study, to look at the effectiveness of a cholesterol-lowering drug to reduce cardiovascular disease. Both studies in the trial began in 1994. Participants were followed for an average of just under 5 years.
The treatment and complications of hypertension are estimated to cost the nation $37 billion annually, with drug costs alone accounting for an estimated $15 billion per year. There is conclusive evidence that blood pressure medications can substantially reduce the risk of heart attacks, strokes and heart failure. However, the best choice for which drug to start therapy with was not known. Until now.
Earlier studies showed the benefit of lowering blood pressure using primarily diuretics or beta-blockers. After these studies, several newer types of drugs such as angiotensin-converting-enzyme (or ACE) inhibitors, calcium channel blockers, alpha-adrenergic blockers, and, more recently, angiotensin receptor blockers became available. Over the past decade, major trials have documented that ACE inhibitors and calcium channel blockers reduce cardiovascular disease in individuals with hypertension. However, these agents were compared with placebo and their relative value compared with older, less expensive agents remained unclear.
The blood pressure study was a randomized, double-blind trial designed to determine whether the occurrence of heart attacks, strokes, and other forms of cardiovascular disease is lower for high-risk hypertensive patients treated with a calcium channel blocker, an ACE inhibitor, or an alpha blocker, each compared with a diuretic. The study involved 42,418 participants aged 55 and older, and was conducted at 623 clinical sites across the continental United States and in Canada, Puerto Rico, and the U.S. Virgin Islands. About 7,000 U.S. veterans participated in the study through 69 Department of Veterans Affairs clinics.
All of the participants had hypertension, or blood pressure of 140/90 mm Hg or higher. They also all had at least one other risk factor for heart disease, such as type 2 diabetes or cigarette smoking.
Participants in the high blood pressure study were randomly assigned to receive one of four drugs: a diuretic (chlorthalidone); a calcium channel blocker (amlodipine); an ACE inhibitor (lisinopril); and an alpha blocker (doxazosin). Other drugs were provided for patients who needed them to achieve blood pressure control.
All participants underwent medical checkups every 3 months during their first year in the study, then every 4 months after that. The mean age of participants at enrollment was 67. About 47 percent of the participants were women, 47 percent white, 35 percent black, 19 percent Hispanic, and 36 percent had type 2 diabetes.
As Dr. Lenfant noted, the alpha-adrenergic blocker arm of the study was stopped in March 2000 because those on the drug had 25 percent more cardiovascular events and were twice as likely to be hospitalized for heart failure as those treated with the diuretic. Our other presenters will describe the final results of the other drugs evaluated in the ALLHAT hypertension study.
Some 10,400 ALLHAT hypertension participants were also part of the ALLHAT cholesterol study. These individuals had slightly elevated blood cholesterol but did not need cholesterol-lowering medication at the start of the trial. They also had at least one heart disease risk factor in addition to high blood pressure and elevated cholesterol. About 14 percent had heart disease at the start of the study and 35 percent had type 2 diabetes.
The study's primary purpose was to determine whether participants assigned to receive a statin drug, in this case, pravastatin, would have fewer deaths compared with those who received "usual care." Both groups were advised to follow a cholesterol-lowering diet. Patients in the usual care group were also prescribed cholesterol-lowering drug therapy--but not necessarily pravastatin-- if their physician determined that changes in their health warranted it.
The ALLHAT cholesterol study was not blinded, so participants and their health care providers knew what treatment they received. The mean age of participants when they enrolled was 66 years. Like the participants in the ALLHAT hypertension study, the subset of participants in the cholesterol study included a strong representation of older persons, women, racial and ethnic groups, and patients with diabetes--individuals who had previously been excluded or under-represented in earlier cholesterol treatment trials.