CHICAGO, IL—In patients implanted with a second-generation paclitaxel-eluting stent (PES), 30 months of dual antiplatelet therapy (DAPT) with prasugrel is more effective than 12 months of treatment in protecting against ischemic events, especially myocardial infarction (MI), according to data presented November 16, 2014, at the American Heart Association Scientific Sessions. Moreover, longer antiplatelet therapy does not increase major bleeding.

In the Taxus Liberté Post-Approval Study (TL-PAS), Kirk N. Garratt, MD, of Lenox Hill Heart and Vascular Institute (New York, NY), and colleagues evaluated the long-term safety and efficacy of the Taxus Liberté stent (Boston Scientific) in conjunction with prasugrel (Effient; Eli Lilly/Daiichi Sankyo) in a broad range of patients.

Cohort Integrated into DAPT Study 

A randomized phase of the study was designed to contribute patients to the landmark DAPT Study, whose results were also presented at the meeting. Twelve months after stent implantation, patients who had been compliant with prasugrel therapy and were free from ischemic or bleeding events were randomly assigned to an additional 18 months of prasugrel (n = 1,098) or placebo (n = 1,093). At 30 months, the study drugs were stopped and patients continued on aspirin alone through at least 33 months after stent placement.

Eighteen months after randomization, cumulative rates of MACCE (all-cause death, MI, or stroke) and definite/probable stent thrombosis—the co-primary efficacy endpoints—were lower with 30- vs 12-month DAPT, with the difference in MACCE driven by a higher incidence of MI. There was no difference between the groups in rates of GUSTO moderate or severe bleeding (table 1). 

Dr. Garratt noted that the difference in MACCE between the groups was evident within 90 days of randomization, and that events accrued much faster shortly after patients stopped DAPT at 30 months. Interestingly, the difference in MI between the groups was similar regardless of whether it was related to stent thrombosis, and nonthrombosis-related MIs were more prevalent in both groups.

In mid-2013 the study Data Monitoring Committee recommended that randomized treatment be unblinded to give participants who had not completed 30-month follow-up the chance to consider open-label prasugrel, but this affected only a small number of patients and had minimal impact on the DAPT Study, Dr. Garratt noted.

He acknowledged that TL-PAS was underpowered for the DAPT Study endpoints and excluded patients with a history of cerebrovascular or bleeding events. In addition, those with very low body mass or advanced age may have been underrepresented. Also, patients eligible for randomization had already tolerated 12 months of prasugrel plus aspirin without major bleeding. 

Dr. Garratt commented that whether the reduction in late ischemic events shown with prasugrel and aspirin after Taxus Liberté implantation “would be observed with other dual antiplatelet regimens and/or other DES will require further insights from the larger DAPT Study.”

Commenting on the study, Gilles Montalescot, MD, PhD, of Centre Hospitalier Universitaire Pitié-Salpêtrière (Paris, France), observed that paclitaxel DES may present an extra risk for stent thrombosis, yet prasugrel was highly effective in preventing such events. One downside, he added, was an apparent rebound effect from withdrawal of the drug. 

Looking at longer DAPT duration is not far from secondary prevention, Dr. Montalescot observed, and raises the possibility of lifelong treatment, especially given evidence that the regimen may also protect not only against stent side effects but also underlying disease. Meanwhile, it makes sense to extend DAPT for those at increased ischemic risk, he said, although separating that risk from bleeding risk can be difficult.

Source:
Garratt KN. Increased risk of ischemic events upon discontinuation of prasugrel after 12 or 30 months of therapy following placement of the Taxus Liberté paclitaxel-eluting coronary stent. Presented at: American Heart Association Scientific Sessions; November 16, 2014; Chicago, IL.

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