AspirinWorks test kit awaits FDA action

New cardiac diagnostic product assesses aspirin’s effect in individual patients through a urine-based assay.

A new diagnostic product for cardiovascular disease that measures a patient’s response to aspirin is in the works and would allow physicians to tailor treatment to a patient’s needs, or recommend alternative therapy.

AspirinWorks test kit (Corgenix Medical Corporation) is a quantitative, enzyme-linked, immunosorbent assay that evaluates levels of 11-dehydrothromboxane B₂ in human urine. This in turn assesses the body’s response to aspirin.

“The uniqueness of this product is that we actually determine thromboxane production, the chemical aspirin is trying to inhibit, by measuring its metabolite 11-dehydrothromboxane B_2; avoiding many analytical variables associated with blood based tests together with ease and convenience of collection to doctors and patients are added benefits,” said Gordon Ens, MT (ASCP), clinical affairs director for Corgenix and president of Creative Clinical Concepts, the biotechnology company that developed AspirinWorks. He said about 10% of patients taking aspirin have a second event such as MI or stroke, demonstrating the prevalence of resistance.

Gordon Ens, MT (ASCP)

“A lot of people think of aspirin as pretty benign, but in the wrong person it has serious adverse events at any dose,” said Raymond Woosley, MD, PhD, president of the Critical Path Institute. “Most people are just given a one-size-fits-all aspirin dose. For some people that’s little and others too much. This test will allow us to know what group people fit into so they get maximum benefit.”

Up to 25% of patients may be nonresponsive to aspirin’s benefits and are more than three times more likely to die of heart disease, according to various reports. This test may address response issues to help physicians determine specific dosage.

“This will provide a biomarker to tell people if they have gotten the dose right for the individual,” said Woosley, also Cardiovascular Pharmacology Section editor of the Today in Cardiology Editorial Board.

Assessing response

Aspirin reduces the amount of thromboxane that is produced in the body, and AspirinWorks measures the amount of this chemical in the body that will have additional effects on platelets.

Platelet function tests require freshly drawn blood and must be evaluated within four hours. AspirinWorks requires a urine sample and is not predisposed to variables associated with blood sample drawing and handling. There are no restraints on when it is processed or tested.

“The benefit is to be able to have a test that actually measures the chemical aspirin is trying to inhibit,” Ens said. “There is an ease and convenience to both patient and doctor you don’t get from other testing methods.”

Concentrations of 11-dehydrothromboxane B₂ are determined by comparing optical densities obtained from the clinical samples to optical densities from a reference curve established from an included kit calibrator.

Reports of previous clinical studies have shown increased levels of 11-dehydrothromboxane B₂ correlate to increased risk for adverse health outcomes, according to Ens. Researchers with the Heart Outcomes Prevention Evaluation (HOPE) study evaluated a subset of patients and tested for levels of 11-dehydrothromboxane B₂ to evaluate aspirin’s effect. The findings of this outcome study showed an increased risk for MI, stroke or cardiac mortality associated with elevated 11-dehydrothromboxane B₂ levels over a five-year follow-up period.

Data from another study, composed of 1,300 asymptomatic individuals, demonstrated a strong correlation between 11-dehydrothromboxane B₂ levels and a high Framingham risk score, and a greater atherosclerotic risk profile, according to Ens.

It is important to note herbal medications, supplements and dietary and lifestyle practices could effect thromboxane production. Since the test results reflect factors that regulate thromboxane production in the body, physicians should assess an accurate and complete diet, lifestyle and medical history of patients.

Where it stands

“[The AspirinWorks test has] been a long time coming and I’m really glad to see it’s hopefully becoming clinically available,” Woosley said. “It could be an important addition to personalized medicine. It’s certainly better than anything currently available.”

Corgenix Medical Corporation submitted a premarket notification to the FDA in July. As of press time, the FDA had not cleared the AspirinWorks test kit for in vitro diagnostic use in the United States.

AspirinWorks Courtesy of Corgenix Medical Corp.

The company launched the kit internationally in the summer of 2006 at the 52nd Annual Scientific and Standardization Committee of the International Society on Thrombosis and Hemostasis, held in Oslo, Norway. It is CE marked in Europe, and kits have been sold in the United Kingdom and other European countries, according to Ens.

“The theory looks great but thorough evaluation by the FDA will be essential,” Woosley said. “This is all based on a lot of data spread over 15 to 20 years. The FDA will have to decide if it is scientifically sound.”

Corgenix, Creative Clinical Concepts and Cayman Chemical Company, a manufacturer of biochemical research products, developed the AspirinWorks test kit. Corgenix and Creative Clinical Concepts have a license agreement with McMaster University, Hamilton, Ontario, that grants the two companies exclusive worldwide rights to the proprietary technology owned by McMaster for the development, manufacturing and marketing of innovative diagnostic tests specific to the pathway by which aspirin acts on platelets.

“Effective management of antiplatelet therapy has the potential to significantly impact patient morbidity and mortality and will require a highly standardized, FDA-regulated test kit,” Ens said.

Future, ongoing studies

Ongoing studies are being conducted at McMaster as well as a number of other sites to evaluate the ability of AspirinWorks to measure the effect of aspirin on platelets, according to Ens.

“Ultimately we are hoping that measuring thromboxane levels will tell us further if the patient is at increased risk of adverse events,” he said. “We see it having huge potential. Additional clinical studies are necessary to make it happen.”

Results from studies conducted in Canada and Australia have shown a positive correlation between AspirinWorks and the research test used in many previous clinical trials, Ens told Today in Cardiology. Data from these and additional comparison studies are scheduled to be presented at the International Society for Thrombosis and Hemostasis meeting in Geneva this July.

“We anticipate clinical studies will continue to show aspirin therapy failure due to too much thromboxane production in some patients taking aspirin. These people would continue to be at increased risk of adverse events,” he said. – by Tara Grassia

For more information:

• To learn more about the AspirinWorks test kit, visit: http://www.aspirinworks.com
• Eikelboom JW, Hirsh J, Weitz JL, et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002;105:1650–1655.