DALLAS, Feb. 3 -- Individuals who take low-dose aspirin to stave off repeat heart attacks or strokes should substitute a higher booster dose twice a month to increase the drug's effectiveness, say researchers today reporting in Circulation: Journal of the American Heart Association.
According to recently issued recommendations from the American Heart Association (AHA), aspirin is advised for individuals who have had a heart attack or stroke or are at high risk due to family history. Prior studies have shown that aspirin offers protection against heart attacks or strokes for only about 25 percent of individuals for whom this inexpensive household drug is appropriate.
The new research suggests that aspirin therapy can work more effectively if a 325-mg booster is taken in place of the lower dose aspirin on the first and 15th of the month.
"Aspirin is not the most ideal agent, but it is one of the best we have and it is the most economical. The goal of our work is to improve therapeutic responsiveness to aspirin," says one of the study's authors Aaron Marcus, M.D., chief, hematology and medical oncology at the Veterans Affairs Medical Center and Cornell University Medical College, New York. Teresa Santos and Juana Balles and colleagues carried out the research at the University Hospital La Fe, Valencia, Spain in collaboration with Marcus' laboratory.
Aspirin helps prevent heart attacks and strokes by blocking the generation of thromboxane, a chemical produced by blood platelets. These disk-shaped blood components accumulate at sites of vascular injury, such as atherosclerotic plaque, and contribute to clot formation. If the blood clot occludes the vessels, which nourishes the heart or brain, a heart attack or stroke occurs.
However, these and other studies from this research group have found that platelets continue to clump, even when aspirin blocks thromboxane formation. The researchers uncovered the reason: When in close proximity to platelets, red blood cells produce substances that stimulate platelets and clot-formation. "This red blood cell-platelet interaction may explain why many individuals respond to aspirin in a less than optimal fashion," says Marcus.
But in their study, researchers found that a single 300-mg dose of aspirin could initially "neutralize" the platelet stimulatory activity of the red blood cells. Subsequent blood tests found that after about two weeks, the red blood cells "escaped from this initial inhibition and began to stimulate platelets again," says Marcus.
To maintain inhibition, a booster dose of 325 mg every two weeks may be needed instead of the lower dose of 81 mg. This schedule reduces the possible gastrointestinal side effects of aspirin, says Marcus.
The results of the study should stir some controversy among physicians who prescribe the same daily dose, without the substitution of a bi-monthly booster. Physicians may require a larger trial to be convinced says Marcus, who has already initiated the twice-month aspirin treatment for his patients.
For individuals who have not experienced coronary artery disease or stroke, aspirin therapy is not recommended unless there is a strong positive family history. "If one or both individual's parents or siblings have had a heart attack before 50, I would consider giving a baby aspirin (81 mg) a day, interrupted by a therapeutic dose every two weeks," Marcus says.
In its latest statement, the AHA recommends a daily dosage of between 75 to 325 mg for such individuals.
The study included 62 individuals from Valencia, Spain who had a heart attack, suffered intractable chest pain, called angina, or had congestive heart failure. The group was given 200 mg of aspirin daily, which is considered a small dose by European standards. Twenty stroke survivors were also included in the study. They received 300 mg of asprin per day. A control group consisted of 200 people who did not take aspirin and 23 individuals who were given a single 500-mg (considered a regular dose by European standards) dose of aspirin.
After three months of aspirin treatment, researchers sampled the participants' blood to test the platelets' ability to respond to stimuli, which causes them to clump. Platelets were tested for clumping in the presence and absence of red blood cells. Thromboxane levels in the blood were also measured.
Even though thromboxane production was inhibited by greater than 94 percent in all individuals taking aspirin, 45 percent of patients still had clumping when red blood cells were present, "indicating a suboptimal response to aspirin." Sixteen percent had clumping even though the red blood cells were not present.
"This latter group may be more thrombosis-prone than the other participants," says Marcus.
In 39 percent of individuals, aspirin blocked clumping in the presence of red blood cells.
"In two thirds of patients, 200-300 milligrams of aspirin was insufficient to block platelet clumping in the presence of red blood cells, despite the fact that aspirin abolished thromboxane synthesis," says Marcus. "Insufficient blocking of this thrombosis-promoting property of red blood cells can lead to additional thrombotic complications."
Eventually individuals will be able to have their blood tested in laboratories to determine whether their platelets are affected by the stimulatory substance produced by red blood cells. That way aspirin treatment can be more tailored, and those who don't require the larger bi-monthy booster can avoid it. Such tests are available in the research setting, but will eventually be used at the bedside.
Media advisory: Dr. Marcus may be reached by calling (212) 686-7500, ext. 3931; fax (212) 951-3389. (Please do not publish telephone or fax numbers.)