May/June 2014

Assessing Aspirin Efficacy for Heart Patients

By Juliann Schaeffer
Today’s Geriatric Medicine
Vol. 7 No. 3 P. 10

Cardiovascular disease kills roughly one in three Americans, which makes heart disease prevention a hot topic among physicians, researchers, and patients. Although there are multiple treatment options available for patients who are at risk of heart attack, not all medication regimens are created equal, differing in cost, time scale, or route of action.

The most common medications prescribed for heart disease patients include antiplatelet or antithrombotic drugs such as aspirin, clopidogrel (Plavix), and eptifibatide (Integrilin). Yet physicians are finding that each medication can work differently for any given patient, and there’s (as of yet) no way to determine which patients will benefit more from one medication over another. “One well-known example is the phenomenon of aspirin resistance, which some studies estimate affects up to 45% of aspirin users,” explains Melissa Li, PhD, a postdoctoral fellow at the University of Washington.

Not all heart disease patients respond to aspirin, and it’s currently unknown exactly why this is the case. “Aspirin resistance” is a sort of catchall term used by physicians for patients who seemingly fail to obtain any benefit from the drug for unknown reasons.

Despite this problem, Li says the majority of physicians continue to prescribe aspirin for most patients and in broadly generalized doses that aren’t patient specific. In an effort to determine why aspirin affects patients differently and to investigate whether it’s possible to determine which medications and respective dosages are most effective for individual patients, Li and researchers from the Georgia Institute of Technology developed a device to simulate blood flowing through narrowed coronary arteries to assess how anticlotting drugs affect different patients.

Study Particulars
Li and Craig Forest, PhD, an assistant professor of bioengineering in the George W. Woodruff School of Mechanical Engineering at Georgia Tech, in collaboration with David Ku, MD, PhD, a mechanical engineering professor at Georgia Tech, conducted the study.

According to Forest, with their efforts, researchers are working toward the potential for a patient at risk of a heart attack and who has been prescribed an antithrombotic drug to one day be able to have blood drawn and tested by this (or a similar) device. Based on the information it would yield, the patient could be prescribed a particular medication that’s most likely to prove beneficial. “That’s where we’re going with this project,” he says.

What exactly is this device? Li describes the disposable microfluidic diagnostic device as a series of branched channels from a single input that directs a patient’s blood sample into various testing areas. “Each branch represents a different flow condition representing different patient disease states [eg, healthy to severely constricted arterial flow],” says Li, who was a graduate student at Georgia Tech during the study. “A nondisposable laser and optical reader provide rapid, noncontact measurements for how quickly platelet clots accumulate within each testing region.”

For the study, which was sponsored by the American Heart Association, a Wallace H. Coulter Foundation Translational Grant, and a fellowship from Georgia Tech’s Technological Innovation: Generating Economic Results program, researchers used the device to test 14 participants’ blood for several factors related to two common heart disease treatments: aspirin and GPIIb/IIIa inhibitors.

Researchers found that the two drugs had very different effects on blood clotting, and that aspirin, while effective for preventing heart attacks in some patients, may not be ideal for everyone, particularly for patients with narrowed arteries.

“The microfluidic diagnostic test allowed us to rapidly scan a number of factors that would help us determine an individual’s optimal medication,” Li says, noting some of the factors researchers tested for included altered blood flow due to preexisting heart disease or plaque formation, different types of drugs, and different concentrations of each drug. “Using this diagnostic, we found that aspirin resistance was significantly greater in patients who had preexisting blockages in their arteries.”

Li explains that the ability of specific drugs and their respective dosages to stop or slow rates of blood clotting served as the researchers’ primary method for assessing whether treatment was effective because blood clotting is the primary cause of heart attacks, or the main way in which cardiovascular disease can cause death or severe injury.

While Li says she expected many of the study’s findings, since physiology’s influence on drug effectiveness for heart attack prevention has been reported previously in clinical cases, she notes that “this is the first time that we have demonstrated that we can detect this within a medical device prototype.”

Although there are other clinical diagnostics that are similar to this device, Li says this is currently the only device, and corresponding study, that has examined such a wide range of parameters.

Future Possibilities
Li says these study findings support the theory that an alteration in blood flow, which most often occurs as a result of heart disease, is an important and often overlooked factor in choosing medications for patients at risk of heart attack. In the future, with additional research, this type of device may be able to help determine whether aspirin would be effective for patients who have known atherosclerosis and are at high risk of heart attacks. “One relevant scenario might be if a patient with a history of arterial blockages might want to take aspirin due to its convenience,” Li says.

“This test could show that aspirin is not effective for that patient, and perhaps that person may need to pursue alternative treatment methods. “It could also provide a method for drug development companies to improve [treatment] formulations,” she adds.

The Georgia Tech researchers believe that if, at some point, it’s integrated into clinical care, such a device could not only prevent heart attacks but possibly even lower health care costs by offering physicians better guidance on what treatment might work best for individual patients.

More Research Necessary
While Li notes that this research shows great potential for ways in which this device may be used in the future in a clinical setting, she emphasizes that research continues to undergo preclinical testing in an academic research environment and, therefore, any specifics regarding cost and availability are unknown.

For now, Li admits that challenges abound before the device could be considered for a clinical environment. “We still need to test how this device works by doing much larger studies of how clinical outcomes correspond with our diagnostic predictions,” she says. “There’s still a lot of work to be done in the development of this device that is ongoing at Georgia Tech.”

Richard C. Becker, MD, a professor of medicine and the director and physician-in-chief of the University of Cincinnati College of Medicine’s Heart, Lung, and Vascular Institute, is one clinician who envisions the potential for such a device and says these study findings in particular advance the understanding of an important topic. “Microfluidic devices and technology have received attention in the scientific community with the hope that they can be designed to emulate in vivo conditions among patients with atherosclerotic vascular disease,” he says. “The investigators from Georgia Tech may have contributed to an important dialogue, with technology that takes cellular components, parameters, and flow characteristics into consideration, a novel readout of thrombus detachment, and the collective effect of drug therapy.”

However, he notes that the true test lies in determining whether the researchers can translate their observations to a quantifiable benefit among patients with atherosclerotic coronary artery disease and says any talk of integrating such a device into clinical care is premature. “Clinical trials of persons at risk for vascular events, including heart attack, stroke, and sudden death, would be the ideal environment as a starting point,” he says. “Once studied, and if shown to offer insight, one could consider its use in risk prediction models that have been employed by the American Heart Association and European Society of Cardiology, among others. The benefit would then require validation.

“Until the appropriate level of investigation has been undertaken, the public should not, in my opinion, be led to believe that this device, while soundly based, is ready for integration,” he adds.

Li agrees and notes that while this research offers significant promise, it will be some time before any similar device finds its way to physicians’ heart disease prevention tool kits. “We’re excited to make advances toward point-of-care diagnostics, but I hope that people aren’t holding their breath for this to be available soon.”

— Juliann Schaeffer is a freelance writer and editor based in Alburtis, Pennsylvania.