The goal of ALLHAT was to provide new information about treating two major risk factors for heart disease: high blood pressure, also called hypertension, and high cholesterol. ALLHAT, supported by the National Heart, Lung, and Blood Institute (NHLBI), began in 1994 and lasted eight years. ALLHAT was the largest trial of treatments for high blood pressure and the second-largest trial of treatments for high cholesterol.
The ALLHAT blood pressure trial compared the effects of three blood pressure-lowering drugs—a calcium channel blocker (amlodipine), an angiotensin converting enzyme (ACE) inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin)—with the effects of a diuretic (chlorthalidone), which was the control treatment in the trial. During the 1980s and early 1990s, the use of diuretics to treat high blood pressure had declined as use of the other drugs had increased.
The ALLHAT cholesterol trial enrolled participants in the blood pressure trial who had moderately elevated cholesterol. The blood pressure and cholesterol trials were conducted concurrently.
The cholesterol trial compared two groups of participants. One group received a cholesterol-lowering statin drug (pravastatin) in addition to the usual care for moderately elevated cholesterol. The other group received only the usual care. When the study began, the usual care included advice about dietary modification and no cholesterol-lowering drug. However, over the eight years the trial was conducted, the usual care evolved to include statins, some of which were more potent than pravastatin.
Key findings from the ALLHAT blood pressure trial
The ALLHAT blood pressure trial found that the calcium channel blocker, ACE inhibitor, and alpha-adrenergic blocker did not work better than the diuretic to control high blood pressure and prevent stroke and some forms of heart disease, including heart attack and heart failure. Compared to the diuretic, the alpha-adrenergic blocker was less effective at controlling high blood pressure and was associated with much higher heart failure rates. Researchers stopped the study of this drug a year early.
ALLHAT’s findings led to the following recommendations:
Other studies have also informed clinical care for high blood pressure. For example, ALLHAT did not study beta blockers, but previous trials have found that beta blockers lower blood pressure and prevent heart problems and strokes. Beta blockers were offered to ALLHAT participants whose blood pressure did not respond to initial treatment.
Key findings from the ALLHAT cholesterol pressure trial
The ALLHAT cholesterol trial compared two groups of participants: the statin group and the usual care group. For the statin group, the trial provided a cholesterol-lowering statin drug and advice about dietary modification. For the usual care group, the trial provided only advice about dietary modification, which was the usual care when the study began. However, doctors prescribed cholesterol-lowering drugs, when needed, for their patients in the usual care group. Over the course of the trial, about 30 percent of participants in the usual care group received a cholesterol lowering drug.
By the end of the study, both groups had significantly lower cholesterol. The trial showed no significant difference between the statin group and the usual care group, probably because over the eight years the trial was conducted, the usual care evolved to include statins, some of which were more potent than pravastatin. Total cholesterol dropped by 17.2 percent among patients in the statin group and 7.6 percent in the usual care group. Researchers did not find a difference in death rates between the two groups. Researchers found slightly lower rates of heart attacks and strokes among patients in the statin group, but the differences in rates between the two groups of patients were not significant.
The ALLHAT cholesterol trial lasted about eight years, and, during that time, other trials showed that statins were effective cholesterol-lowering drugs. In 2001, national guidelines changed to recommend statins for more patients. Because some ALLHAT results published in 2002 were in line with the results of other statins studies, ALLHAT did not change cholesterol treatment guidelines, which already recommended lifestyle changes and drug therapy to lower cholesterol and reduce the risk of developing or dying from heart disease, a heart attack, or a stroke.
ALLHAT consisted of two trials: the blood pressure trial and the cholesterol trial. All participants underwent medical checkups at three, six, nine, and 12 months after entry into the study, and every four months after that.
The ALLHAT blood pressure trial
The ALLHAT blood pressure trial involved more than 42,000 participants ages 55 and older. Participants had high blood pressure and at least one other risk factor for heart disease, such as cigarette smoking or type 2 diabetes.
The trial was conducted at more than 600 clinics and centers across the United States and in Canada, Puerto Rico, and the U.S. Virgin Islands.
Participants were randomly assigned to receive one of the four blood pressure-lowering drugs in the study. The study was a double-blind trial, meaning that neither the researchers nor the participants knew which participants received which drug. The trial compared different medicines in patients who commonly need at least two or three medicines to control their high blood pressure. Other medicines were available to supplement the initial treatment if the participant’s blood pressure did not respond to the initial treatment. The study followed participants for an average of 4.9 years.
Researchers stopped the study of the alpha-adrenergic blocker drug a year early, because participants taking this drug had substantially more cardiovascular problems than participants taking the diuretic. The trial ended in 2002, and researchers published the results in December 2002.
The ALLHAT cholesterol trial
The ALLHAT cholesterol trial involved more than 10,000 participants from the blood pressure trial. At the start of the study, all participants had moderately elevated cholesterol, and their doctors decided that the use of cholesterol-lowering drugs was optional for these patients.
Researchers divided participants into two groups: one group received a cholesterol-lowering statin drug along with the usual care, and the other group received only the usual care. The usual care included dietary modification and no cholesterol-lowering drugs. However, during the trial, doctors prescribed cholesterol-lowering drugs for some participants in the usual care group. Doctors prescribed these drugs when needed due to changes in a patient’s condition, such as a heart attack or an increase in cholesterol levels. Also, over the eight years the trial was conducted, clinical practice changed. By the time the study ended, many doctors felt that statins were a required part of the usual care for patients who had moderately elevated cholesterol.
The cholesterol trial was not blinded, meaning that participants and their health care providers knew what treatment participants were receiving. The study followed the participants for an average of 4.8 years. The trial ended in 2002, and researchers published the results in December 2002.
Recent NHLBI research on high blood pressure includes SPRINT. This trial, which enrolled adults ages 50 years or older, found that intensive management of systolic blood pressure to a lower target reduced rates of complications of high blood pressure and lowered the risk of death.