ASCET: Single antiplatelet therapies compared in stable CAD

Patients with stable coronary artery disease (CAD) who require single antiplatelet therapy and who are nonresponsive to aspirin should probably switch to clopidogrel, says the lead author of a new study, Aspirin Nonresponsiveness and Clopidogrel Endpoint (ASCET), which was presented at the American Heart Association (AHA) 2010 Scientific Sessions last week. The discussant of the trial agrees that aspirin nonresponders should switch therapy, but argues that they would be better off on a more potent antiplatelet agent than clopidogrel.

ASCET author Dr Alf-Aage Pettersen (Oslo University Hospital, Norway) explained to heartwire that patients with stable CAD still have a high risk for thromboembolic events and can be on a single antiplatelet agent for many, many years, so the question of which drug is best for reducing risk in a specific patient "is very important."

ASCET is the only other study, apart from the landmark CAPRIE trial, to examine the issue of single antiplatelet therapy and to compare aspirin with clopidogrel in patients at risk of ischemic events, he noted. ASCET examined whether patients with high platelet reactivity on aspirin (nonresponders) had worse clinical outcomes than aspirin responders, and also if aspirin nonresponders fared better by switching to clopidogrel.

"The answer to both questions was no, this was a negative trial," discussant Dr Jurrien M ten Berg(St Antonius Hospital, Nieuwegein, the Netherlands) told heartwire. However, says ten Berg, the absolute reduction in the primary composite endpoint seen in aspirin nonresponders who switched to clopidogrel compared with those who stayed on aspirin was "quite striking," he noted, adding that the trial was "really underpowered" to demonstrate a significant difference "but I guess the essence is real."

However, ten Berg says he doesn't think clopidogrel is a great choice of agent to switch to, because studies have shown that 50% of patients who are resistant to aspirin will also be resistant to clopidogrel. A stronger antiplatelet agent, such as the investigational agent, ticagrelor, would be a better choice, he noted, although he conceded that cost may be a limiting factor in choice of therapy in many instances. A more potent antiplatelet agent might be a particularly good option for secondary prevention in high-risk patients, such as those with diabetes, he noted.