This article is more than 5 years old. Information may no longer be current.
Aspirin resistance may require a change in antiplatelet therapy
The VerifyNow test is proving its value as a quantitative device.
Click Here to Manage Email Alerts
Aspirin resistance — and what can be done for patients who do not respond to aspirin — has interventional cardiology abuzz. Likewise, the VerifyNow Aspirin Test from Accumetrics is emerging as an important tool to aid clinicians in quantifying aspirin resistance in their patients.
“It’s always been intriguing that antiplatelet therapy has been shotgunned as a one-dose-fits-all regimen,” said Daniel Simon, MD, associate professor of medicine at Harvard Medical School and associate director of interventional cardiology at Brigham and Women’s Hospital. “Regardless of the patient’s size or weight, they get the same dose of aspirin and clopidogrel [Plavix, Sanofi Synthelabo].”
According to Simon, the VerifyNow device is helping to grow a body of data and studies showing that resistance is a marker of adverse outcomes and that modifying therapy in these patients may likely be necessary to improve outcomes.
|
|
Shotgunned therapy
Recent research presented at the American College of Cardiology Scientific Session 2005 showed that up to 27% of aspirin users with coronary artery disease (n=478) were resistant to the antiplatelet effects of aspirin, and that women, the elderly, those with renal insufficiency, low hemoglobin levels and those taking low-dose aspirin were most likely to be resistant. Aspirin dosage directly correlated with the prevalence of resistance: It was highest with less than 100 mg (30.2%), lower with 150 mg (16.7%), and nonexistent with 300 mg (0%). This finding was atypical of most aspirin responsiveness studies, however, according to Simon.
Research was also presented showing that resistance to aspirin and clopidogrel may occur together in patients undergoing percutaneous coronary intervention (PCI), according to a press release.
As antiplatelet strategies have evolved in the catheterization lab, more and more clinicians are only using aspirin and clopidogrel in a substantial fraction of their patients, Simon said. It’s estimated that in the United States and Europe, upwards of 40% of patients undergoing angioplasty are being given aspirin, clopidogrel and heparin alone. In this way, “the concept of aspirin and clopidogrel nonresponsiveness becomes critical,” Simon said.
In their own study to quantify the prevalence of aspirin nonresponsiveness, Simon and his colleagues examined patients at four centers (n=422) who presented to the catheterization lab. The VerifyNow test was used in this study as well.
They found an aspirin nonresponsive rate of 23% that was independent of aspirin dosage; no difference in the rate of aspirin nonresponsiveness was found with 325 mg compared with 81 mg. The only independent predictor of aspirin nonresponse was the presence of CAD, which doubled the relative risk.
“That has substantial implications,” Simon said. “If 20% to 25% of the patients that come into the cath lab are aspirin nonresponsive, what does that mean for their outcomes when they’re going through angioplasty with aspirin, clopidogrel and heparin alone?”
A study that Simon was not involved in but that also used the VerifyNow device found that patients who were aspirin nonresponsive had a two to fivefold increased risk of myonecrosis or MI after angioplasty.
“If you’re aspirin nonresponsive, and you go on to a procedure and have a two to five fold increased risk of heart attack, then shouldn’t we potentially be changing the way we treat patients?” Simon said.
Three-step process
Running a patient test using VerifyNow is done in three steps. A disposable assay device is inserted into the system, and then a specimen tube with two mL of whole blood is inserted into the assay device. In less than 10 minutes, the result, measured in Aspirin Reaction Units (ARUs), is displayed.
|
Photo courtesy of Accumetrics |
Less than 550 ARUs indicates that aspirin is adequately working; greater than 550 ARUs indicates that aspirin is not having a desired effect.
Simon described VerifyNow as “a simple device that can be performed at the bedside, that has a turnaround time that a physician would actually act on, that doesn’t need to be done in the hematology setting, and that could basically be done by anybody.”
Aspirin testing currently can be likened to cholesterol measuring of a little over a decade ago. “We knew that elevated cholesterol was a marker of risk. We measured it because we wanted to know if people were at risk,” he said.
“We measured cholesterol for a decade and a half before there was any evidence that lowering it improved outcome. It took a randomized study before people became convinced that that was the case.”
Simon believes physicians are going to gradually start coming around to the concept that patients who are aspirin and clopidogrel nonresponsive have adverse outcomes.
“Now, we’re trying to show in randomized studies that if you change therapy based on platelet function tests, you improve outcome. We haven’t quite closed the loop yet; but just like in the cholesterol testing phase, we knew it was elevated, we knew it was associated with adverse risk, we measured it for prognostic purposes, and then we waited for trials to show that changing therapy absolutely improved outcome,” he said.
Simon hopes to help close this loop. He is set to be the national principal investigator of the RESISTOR (Research Evaluation to Study Individuals who Show Thromboxane or P2Y12-Receptor Resistance) trial, an upcoming 30-center, prospective, randomized study that will examine different antithrombotic strategies in the catheterization lab to address aspirin and clopidogrel nonresponsive patients undergoing angioplasty.
Suggestions for treatment
There are variable suggestions about what to do if a patient is nonresponsive, from adjusting the dosage to helping increase compliance by simply telling patients to take the aspirin.
“There are some data that enteric vs. nonenteric coating makes a difference. If your patient was on an enteric-coated preparation or was on 81 mg and was nonresponsive, you could increase the dosage and see if they responded,” he said. “What most of us do, though, is to strongly consider adding clopidogrel to the patient’s regimen.”
Simon believes that clinicians will tailor antiplatelet therapy just as other antithrombotic therapy is tailored. “We don’t ‘shotgun’ coumadin doses to fixed-dose, we don’t treat with fixed-dose heparin, we don’t treat with fixed doses of anticoagulants in the cath lab. What we’re saying is one size doesn’t fit all, and patients’ antiplatelet therapy needs to be adjusted,” Simon said. – by Evan Young
RESISTOR, the upcoming trial for which Daniel Simon, MD, is the national principal investigator, will be cosponsored by Accumetrics. Accumetrics is one of three sponsors of the trial. Simon has no financial interest in the product mentioned in this article, nor is he a paid consultant for the company mentioned.