Kirk Garratt, MD, presenting at the 2014 American Heart Association Scientific Sessions, said "The TAXUS Liberte Post-approval Study (TL-PAS) was designed to provide long-term safety and efficacy information about the clinical outcomes for the TL stent combined with the use of prasugrel and aspirin."
Kirk Garratt, MD, Lenox Hill Heart and Vascular Institute, New York, NY presented at the American Heart Association (AHA) Scientific Sessions 2014,“The TAXUS Liberte Post-approval Study (TL-PAS) was designed to provide long-term safety and efficacy information about the clinical outcomes for the TL stent combined with the use of prasugrel and aspirin.“
A portion of patients from TL-PAS contributed to the Dual Anti-Platelet Therapy (DAPT) Trial. Initially, a total of 4,199 US patients treated with TL stents were enrolled in TL-PAS. Only 3,904 met the inclusion and exclusion criteria and were thus recruited for participation in the DAPT trial. They received open-label prasugrel plus aspirin for 12 months following stent placement. At the 12-month mark, 2,202 patients who didn’t experience ischemic or bleeding events continued aspirin therapy and were randomized equally to continue blinded treatment with either prasugrel or placebo for an additional 18 months. At 30 months, study drugs were discontinued, and aspirin was continued through at least 33 months after stent placement. Events were adjudicated by a clinical events committee and monitored by the TL-PAS Data Monitoring Committee (DMC).
Garratt studied two co-primary effectiveness endpoints: “The first major adverse party of cerebral vascular events was defined as all-cause mortality, myocardial infarction, or stroke. The second was stent thrombosis. The principal safety endpoint that was studied was major bleeding defined as moderate or severe bleeding.”
Approximately 3 years after randomization, the DMC noted a significant increase in spontaneous ischemic events after prasugrel therapy withdrawal in randomized patients. This risk was observed in both the patients who switched to placebo following 12 months DAPT and in patients randomized to blinded prasugrel who had completed an additional 18 months of drug therapy. As a result, DMC recommended that treatment be unblinded for TL-PAS patients when they completed 18 months of randomized drug treatment. The hoped to potentially continue prasugrel in those patients randomized to the active drug arm.
An increased risk of ischemic events was observed after prasugrel cessation in patients randomized to either 12 months or 30 months of DAPT following placement of a TAXUS Liberte paclitaxel-eluting coronary stent and prompted recommendation for unblinding of therapy by DMC.
Garratt said, “We evaluated the relationship between stent thrombosis and myocardial infarction. We found that no defined myocardial infarction could be attributed to stent thrombosis in the patients who continued prasugrel plus aspirin for 30 months; however, this was observed in 2.6% of the patients who took prasugrel plus aspirin for 12 months. “
This analysis had certain limitations, although it was very specified, those with low body mass and significant older age may have been underrepresented. Patients who were randomized demonstrated tolerance
Garratt concluded, “We find that compared to 12 months therapy, patients receiving TAXUS Liberte Paclitaxel-eluting stents who were treated with prasugrel and aspirin for 30 months experienced a significant reduction in major adverse cardiac and cerebral events in stent thrombosis. This chief clinical benefit was a reduction in myocardial infarction related to stent thrombosis, a modest increase is observed, but no increase in severe bleeding or hemorrhage was seen.”
He further observed a withdrawal of prasugrel resulted in an apparent loss of protection with an early rise in ischemic events when discontinued after 12 or 30 months. “The principle risk in these patients was an increase in myocardial infarction and the impact was evident within 30 days.”