By Lisa Fratt
Aspirin is the frontline therapy used to protect patients from cardiovascular disease and stroke.
In the United States alone, 25 million to 30 million people take aspirin on a daily basis to prevent cardiovascular disease and stroke. Physicians typically prescribe at-risk patients a low, daily dose of aspirin. Aspirin has cardiac-care applications as well. For example, aspirin, in conjunction with Plavix, is administered prior to coronary stenting procedures to lessen complications from the procedure.
Until recently, the medical community had generally accepted aspirin’s utility and efficacy for preventing heart attack, stroke, and other cardiovascular events. And aspirin is one of the most effective drugs in this capacity; however, the medical community has realized that aspirin’s effectiveness is not universal. Recent research shows that it is essential to confirm on an individual basis that aspirin is providing antiplatelet benefits with the current dosage prescribed.
A universal prescription for aspirin and other therapeutic agents may not be the best approach to patient care. In fact, randomized clinical trials have demonstrated that there are a variety of reasons, including genetics, weight, and other factors, that a patient’s response to a given agent is individual and cannot be predicted based on the results of other patients.
Daniel Simon, MD, associate director, Interventional Cardiology at Brigham and Women’s Hospital in Boston, and associate professor of medicine at Harvard Medical School, says the one-size-fits-all approach to medicine is gradually being replaced by personalized medicine. Physicians are examining therapies administered on the basis of weight or a fixed dose and asking whether or not they are effective. The individual nature of a patient’s response to medication is particularly striking with aspirin. “Aspirin nonresponsiveness is the poster child for the personalized medicine approach,” says Simon.
The research is overwhelming. Studies have demonstrated that 24% to 30% of patients are either nonresponsive or resistant to aspirin’s antiplatelet effects. Moreover, other studies have shown that nonresponsive and resistant patients are at an increased risk for adverse outcomes and death from myocardial infarction. Some studies have linked aspirin resistance with triple the risk of heart attack, stroke, and death in patients with cardiovascular disease. Studies also put aspirin-resistant patients at a greatly increased risk of vascular events in the 2 years following stroke. Robert Hillman, CEO of Accumetrics in San Diego, sums it up, “A broad range of studies have shown that aspirin resistance exists and that patients who are aspirin resistant or nonresponsive have a higher incidence of adverse outcomes from both cardiovascular disease and stroke. What is really stunning, however, is that patients and physicians may not realize that aspirin therapy is not working.”
Determining whether or not aspirin is working for an individual patient is critical because other medication can provide similar protection. In an ideal world, physicians would have specific information about a patient’s response to aspirin prior to resorting to prescription medication.
The Next Step
“What’s been missing over the years is a simple way to measure aspirin resistance,” Hillman says. The gold standard for measuring platelet aggregation and the effectiveness of aspirin and other antiplatelet agents is platelet aggregometry. Platelet aggregometry, however, is far from an ideal solution. For starters, the test is not available in all hospitals. Even in hospitals where platelet aggregometry is performed, the test can be prohibitively expensive; it takes hours and a skilled technician to complete the test. The upshot? Platelet aggregometry cannot be used on a routine clinical basis to determine aspirin nonresponsiveness or aspirin resistance.
The clear solution is a simple, cost-efficient test that can be used to identify patients who are nonresponsive or resistant to aspirin. Last fall, the Food and Drug Administration (FDA) cleared the VerifyNow aspirin test from Accumetrics. The new test is the first rapid, point-of-care diagnostic test that can be used to inexpensively test a patient’s response to aspirin.
The 10-minute test consists of a disposable assay device that contains all of the necessary reagents in a lightweight bedside instrument. The lab technician inserts the assay device into the instrument and adds a small tube of blood. The instrument completes the testing process by measuring the degree to which a patient’s platelets aggregate and displays the results. The results are reported in aspirin reaction units (ARUs). A value above 550 ARUs indicates that aspirin is not working, and a value below 550 ARUs shows that aspirin is working. “We’ve made a previously complex procedure simple,” Hillman says. “VerifyNow is a tremendous labor and cost savings over platelet aggregometry.” Although the test is simple, it is also sensitive and specific. VerifyNow is sensitive to all dosing levels of aspirin, including the commonly prescribed low dosage of 81 mg.
Unlike platelet aggregometry, VerifyNow does not require a specialized technician. The test and its results can be made available to physicians at any hour of the day. In addition to the assay device and instrument, VerifyNow also includes quality control materials and protocols to address standards for accreditation.
Because VerifyNow removes clinical uncertainties associated with aspirin therapy the test may also help physicians prevent adverse outcomes. “VerifyNow allows physicians to tailor therapy to improve patient outcomes,” Simon says. After determining that a patient is aspirin resistant or nonresponsive, a physician may increase the prescribed aspirin dose or add a different agent to potentially avert an adverse outcome. In some cases, the only change in therapy is a bit of patient education. The patient may not be complying with aspirin therapy or he may be aspirin resistant because he is combining aspirin with an agent that blocks the aspirin receptors. For example, ibuprofen can interfere with aspirin-based antiplatelet therapy. In either case, patient education typically solves the problem.
Other cases require a higher dose of aspirin. And some patients need a prescription for an antiplatelet medication, typically Plavix. Plavix is often not an appropriate first-response therapy because it costs $3–$6 per day. But when physicians and their patients see VerifyNow results demonstrating an ineffective response to aspirin, they may be more likely to accept dual antiplatelet therapy consisting of aspirin and Plavix. The VerifyNow aspirin test can also be used to assess the effects of combined antiplatelet therapy, such as aspirin combined with Plavix. The test also allows physicians to avoid “shotgun” treatment, in which a treatment, such as Plavix or aspirin, is universally applied. Instead it facilitates the personalized medicine approach.
Applications and Settings
VerifyNow may be deployed in a number of hospital departments. Currently, nearly 50 hospitals have implemented VerifyNow in a variety of settings including the clinical lab, emergency room, cath lab, or stroke clinic. “Laboratorians in these sites have been impressed with the simplicity of our platelet function test,” Hillman says.
VerifyNow can be used for any patient on aspirin therapy to let the physician know whether or not the patient is fully protected by aspirin. It is also important to implement follow-up testing after the initial aspirin response determinations have been made. Studies have shown that the effectiveness of aspirin can fluctuate and decrease over time, potentially leading to life-threatening cardiovascular events. Ideally, a patient’s aspirin responsiveness would be measured on an annual basis. In addition, the test would provide valuable information any time a patient is admitted to the hospital with a heart attack, indicating the current treatment regimen is not working.
Simon at Brigham and Women’s Hospital conducted one of the first studies of VerifyNow and anticipates implementing the test as a clinical tool in the hospital in the near future. With 15 million to 20 million patients in the United States affected by coronary disease and/or cerebrovascular disease, Simon believes the real venue for VerifyNow is the outpatient sphere.
The current CLIA designation for VerifyNow is moderately complex with CLIA waiver status expected soon. Many physician offices can perform VerifyNow and other moderately complex tests. In fact, a number of cardiology practices, internal medicine offices, and general practitioners are currently using the test.
Platelet Function Testing in the Future
Hillman sees VerifyNow as the first in a family of platelet function testing devices. VerifyNow 2b3a, for example, is also FDA cleared and may be used to monitor intravenous antiplatelet agents, such as Integrilin. Accumetrics is also developing a test to measure the effectiveness of Plavix. Each simple test can be readily integrated into the work flow of the lab. The results, however, are fairly far reaching as they allow physicians to tailor therapy to each patient’s needs.
Lisa Fratt is a contributing writer for Clinical Lab Products.
