Jeffrey L. Probstfield, M.D.
ALLHAT Steering Committee
Clinical Trials Service Unit
Professor of Medicine and Epidemiology
University of Washington Health Sciences Center
December 17, 2002
Press Conference Remarks
Release of Results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: Findings of the Lipid Lowering Study
Thank you, Dr. Wright.
Dr. Davis has outlined the design of ALLHAT's lipid-lowering study. The study's key lipid question was whether use of a statin drug would reduce deaths from all causes more than following usual care in patients with relatively well-controlled high blood pressure and at least one other risk factor for cardiovascular disease. This study included participants not sufficiently represented in prior cholesterol-lowering trials--namely, women, older persons, African Americans and other minority groups, and people with type 2 diabetes. The criteria used to enroll participants in the ALLHAT study were designed to admit those who had no clearly established need for cholesterol-lowering drugs according to the then-current clinical guidelines.
After 4 years, total cholesterol dropped by about 17 percent in the pravastatin group and about 8 percent in the usual care group. LDL cholesterol fell by about 28 percent in the pravastatin group and 11 percent in the usual care group.
There were 631 deaths in the pravastatin group and 641 deaths in the usual care group; 380 coronary heart disease events in the pravastatin group and 421 heart disease events in the usual care group; and 209 strokes in the pravastatin group and 231 strokes in the usual care group. Heart failure and cancer rates were similar in the two groups.
The study found no difference in the death rates from all causes between the two groups.
The rate of fatal and non-fatal coronary heart disease events was 9 percent less in the statin group than the usual care group-not a statistically significant difference.
The findings for ALLHAT's subgroups were similar to the overall results. The subgroups were defined at baseline by participants' primary blood pressure-lowering treatment or levels of total cholesterol and low-density lipoprotein, presence or absence of cardiovascular disease or type 2 diabetes, gender, age, and racial or ethnic group.
At the start of ALLHAT's lipid-lowering study, the investigators were urged to put into it only those participants in the hypertension trial whom they felt would not need a cholesterol-lowering drug. However, during the trial, a significant percent of those in the usual care group did begin to take a statin or other cholesterol-lowering drug, often because of a change in their cardiovascular disease status, such as the occurrence of a heart attack or other vascular disease. Thirty percent of those in the usual care group used a cholesterol-lowering drug-most often, a statin-at some time during the trial.
As a result, the decreases in levels of total and LDL cholesterol in ALLHAT's usual care group were substantially greater than the reductions seen in placebo groups of other large cholesterol-lowering trials. Therefore, the differences in cholesterol levels between ALLHAT's usual care and statin groups were substantially smaller than those between the drug and placebo groups of other lipid trials. This is likely why we did not detect in ALLHAT the impact of the statin on heart attacks and deaths that were seen in other statin trials.
The absence of a significant reduction in deaths in ALLHAT's results is unlikely to be related to the effect of the particular statin used. Other trials have shown that the drug-pravastatin-does reduce deaths and heart attacks.
Also, subgroup analyses provide no basis for concluding that cholesterol-lowering treatment is less effective for women, the elderly, African Americans, or persons with high blood pressure.
Thus, ALLHAT's results on deaths and heart attacks are consistent with findings from other lipid-lowering trials, given the observed reductions in cholesterol. ALLHAT's findings do not alter current guidelines on the treatment of high cholesterol. Lowering elevated cholesterol levels through lifestyle changes and drug treatment remains crucial for the prevention of heart attacks and strokes.
Thank you. Now, I will turn the session over to Dr. Paul Whelton, who will talk about the implications for patients and doctors of ALLHAT's blood pressure- and cholesterol-lowering studies.