乌鸦传媒

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Using rivaroxaban (Xarelto) in the antithrombotic regimen after stenting for patients with atrial fibrillation reduced risk of bleeding better than standard triple therapy, the PIONEER AF-PCI trial showed.

At 1 year, clinically-significant bleeding was less frequent with the combination of the non-vitamin K oral anticoagulant (NOAC) plus a P2Y12 inhibitor (typically clopidogrel) than with the combination of warfarin and dual antiplatelet therapy (16.8% versus 26.7%, HR 0.59, 95% CI 0.47-0.76).

The same was true for a triple therapy regimen of very-low-dose rivaroxaban, a P2Y12 inhibitor, and aspirin (18.0% versus 26.7%, HR 0.63, 95% CI 0.50-0.80), , of Boston's Beth Israel Deaconess Medical Center, reported online in the New England Journal of Medicine and at the American Heart Association meeting in New Orleans.

Clinical outcomes didn't appear to be compromised, with statistically similar composite rates of cardiac death, MI, and stroke as well as of stent thrombosis among the three groups.

In a separate post hoc analysis of the trial published in Circulation, combined all-cause mortality or hospitalization was reduced in the rivaroxaban groups compared to the warfarin control, with an advantage in both the low-dose group (34.9% versus 41.9%, HR 0.79, 95% CI 0.66-0.94, number needed to treat=15) and the "baby-dose" group (31.9% versus 41.9%, HR 0.75, 95% CI 0.62-0.90, number needed to treat=10).

"From the PIONEER data to date, there seem to be significant benefits from abandoning the strategy of full dose triple therapy, with no apparent downside," , of Brigham and Women's Hospital in Boston, wrote in an accompanying editorial.

"For the time being, in patients not in clinical trials, full dose oral triple therapy with dual antiplatelet agents and full dose anticoagulation should be avoided as a routine practice," he concluded.

Notably, the trial was the first to report safety and efficacy of a novel "baby dose" of rivaroxaban -- 2.5 mg b.i.d.

The PIONEER AF-PCI trial included 2,124 participants with non-valvular Afib who had been stented. They were randomized to three groups:

• Low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor -- clopidogrel (Plavix) for more than 80%, or less commonly ticagrelor (Brilinta) or prasugrel (Effient) -- for 12 months
• The "baby-dose" of rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months, at the physician's discretion
• Dose-adjusted warfarin (once daily) plus DAPT for 1, 6, or 12 months, at the physician's discretion

Study discussant , of Hôpital Bichat in Paris, cautioned about wide confidence intervals for the key clinical endpoint of stroke. "This trial does not establish non-inferiority of rivaroxaban-based strategies versus vitamin K antagonists for stroke prevention."

The low number of events, while reassuring, left the trial underpowered, he noted.

While not definitive because the trial wasn't big enough, "the cardiovascular event rates are in the right ballpark for what we would expect," , of the University of Edinburgh and co-chair of the trial, told 乌鸦传媒.

"The reference standard in the past has been vitamin K antagonist and dual antiplatelets, but unlike the WOEST trial, which mandated that the triple therapy went on for 1 year and at potentially augmented bleeding risk in that arm ... the triple therapy was shortened to as short as possible in the reference arm, minimizing the bleeding risk," he noted.

"If we get similar efficacy [with the rivaroxaban arms] and they are of the level we would expect in modern treated patients but much better safety and actually substantially better rates of rehospitalization then that's an impact on our healthcare resources," he said.

Tim Henry, MD, of Cedars-Sinai Medical Center in Los Angeles, cautioned that the 2.5 b.i.d. dose, while available in Europe, is not in the U.S., limiting applicability of the findings.

Still, for a patient group with so little data available to guide treatment, he said, "It's a good start. It's an important population that's increasing in frequency."

There are three other trials ongoing with the other NOACs that "should give us further insight into the optimal antithrombotic cocktail in this challenging subgroup of patients," Bhatt noted.