麻豆传媒

NEW ORLEANS -- After stenting patients with atrial fibrillation (Afib), a course of rivaroxaban (Xarelto) -- in combination with either a P2Y12 inhibitor or dual antiplatelet therapy (DAPT) -- was safer than a warfarin-DAPT combination, a late-breaking trial showed.

At 1 year, than with warfarin/DAPT (16.8% versus 26.7%, HR 0.59, 95% CI 0.47-0.76), the PIONEER AF-PCI investigators found. Bleeding was also less common among those who got a triple therapy regimen of rivaroxaban, a P2Y12 inhibitor, and aspirin (18.0% versus 26.7%, HR 0.63, 95% CI 0.50-0.80).

However, the composite outcome of cardiac death, MI, and stroke was equally likely among groups (6.5% for rivaroxaban/single antiplatelet versus 5.6% for triple therapy versus 6.0% for warfarin/DAPT, P=N.S.), as was stent thrombosis (0.8% versus 0.9% versus 0.7%, P=N.S.), , of Boston's Beth Israel Deaconess Medical Center, told the audience at a late-breaking clinical trial session at the annual American Heart Association meeting here.

But despite the similar efficacy rates, "the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy," Gibson's group cautioned in the paper simultaneously published online in the New England Journal of Medicine.

In particular, when compared to warfarin/DAPT, stroke was not less common with rivaroxaban and a single P2Y12 inhibitor (HR 1.07, 95% CI 0.39-2.96) or with triple therapy (HR 1.36, 95% CI 0.52-3.58).

However, "this trial does not establish noninferiority of rivaroxaban-based strategies vs vitamin K antagonists for stroke prevention," argued discussant , of Hôpital Bichat in Paris, citing the wide confidence intervals for stroke.

The PIONEER AF-PCI trial included 2,124 participants with nonvalvular Afib who had been stented.

Patients 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; a "baby-dose" of rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months; or standard therapy with warfarin (once daily) plus DAPT for 1, 6, or 12 months.

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).

"This paper may be one of those rare circumstances where the secondary post hoc analysis is more insightful than the primary pre-specified analysis, having both greater statistical power and a more clinically relevant endpoint. Of course, from a statistical point of view this may be viewed as a heretical stance, but physicians in actual practice need to make complex decisions with the best available data," , of Brigham and Women's Hospital in Boston, wrote in an accompanying editorial in Circulation.

"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," he concluded. "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."

The trial had several limitations, its authors acknowledged. "First, the secondary analyses showed that the efficacy of each of the two doses of rivaroxaban was similar to that of standard therapy. However, the number of secondary efficacy end points in this study was small, and the trial was not powered to definitively establish either superiority or noninferiority."

And because the rivaroxaban dose was reduced but not that of warfarin/DAPT, Steg asked: "Is this a fair comparison?"

Furthermore, DAPT duration was a major potential confounder.

"Stratification to 1, 6, or 12 months of DAPT was based on clinician choice, and patients were not randomly assigned to a duration of DAPT. As might be expected, patient characteristics were imbalanced across the strata of DAPT durations and within each stratum of DAPT durations across the three treatment groups," according to Gibson and colleagues.