American Heart Association Comment:Lancet (Jan. 24, 1998) report titled "Thrombosis prevention trial; randomized trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men and increased risk"
A combination anticoagulant treatment -- low-dose aspirin and low-dose warfarin -- reduced the risk of heart attack by 34 percent in a 13-year study involving 5,499 men.
Valentin Fuster, M.D., Ph.D., president-elect of the American Heart Association, says the study's findings "open the door" to the exploration of new treatments for preventing heart attack deaths in healthy individuals at high risk. Other studies that have looked at a double-drug approach of aspirin and warfarin but have not found such positive results. "The researchers in the study were able to develop the right dosage so that the benefits outweighed the risk, " says Fuster, director of the Cardiovascular Institute at Mount Sinai Medical Center, New York City. "The use of anticoagulation treatment is a balancing act; it appears they have found the right balance."
Individuals with high blood pressure taking both drugs had the highest risk for bleeding in the brain. "We need to be more concerned about an increased risk of adverse reactions, including hemorrhagic stroke, for individuals who have high blood pressure," says Fuster. Furthermore, because the study was conducted in middle-aged, high-risk men, the benefits of the treatment for other groups, including women, must await further study.
"The study still does not answer the question of whether warfarin and aspirin should be given to healthy individuals without known risk factors," says Fuster. Policy and clinical decisions cannot be based on one study, and physicians still must make individual judgments and weigh the risk and benefits.
In a study published in Lancet last year by Fuster and other researchers involved in the Coumadin Aspirin Reinfarction Study, warfarin in a dose of 3 milligrams/day combined with aspirin in a dose of 80 or 160 mg a day did not provide any benefit beyond that achieved with a 160 mg dose of aspirin alone. In the study published in this week's Lancet, T. W., Meade, M.R.C, and other researchers of the Medical Research Council in London found that individuals given a slightly higher dose of warfarin (4 mg a day) and aspirin (75 mg daily) had lower risk of heart attack.
The study included middle-aged men at increased risk for heart attack because they were in the top 20 percent of a "risk score." The score was derived by combining risk factors such as smoking history, body mass index, blood pressure, cholesterol, fibrinogen (a protein that helps form clots) and factor VII coagulation activity (an indication of the viscosity of the blood).
The study found that compared to placebo, warfarin reduced heart attack by 21 percent and heart attack deaths by 39 percent; low-dose aspirin reduced heart attack risk by 20 percent and reduced heart attack deaths by 32 percent. When the drugs were used together, the risk of all heart attacks (both fatal and non fatal) was reduced by 34 percent compared to those taking placebos. Side effects, including hemorrhagic (bleeding) strokes or aneurysm (a leaking blood vessel in the brain) occurred in 15 individuals who had taken warfarin compared to three who had not. Most of the individuals with stroke had high blood pressure. "Physicians must first make sure that before prescribing the combination, patients must have their high blood pressure controlled," says Fuster.
Researchers say treating 1,000 men with the drugs would avoid five heart attacks a year.