Study: Combined antiplatelet, NOAC use linked to worse limb outcomes after suprainguinal bypass

William Robinson

A new analysis that found combined antiplatelet and novel oral anticoagulant (NOAC) therapy after suprainguinal bypass was associated with worse limb outcomes and equivalent survival compared to antiplatelet use alone has “weaknesses” but is “hypothesis-generating,” the senior author insisted during a scientific session at the 2022 annual meeting of the Midwestern Vascular Surgical Society (MVSS) in Grand Rapids, Michigan (Sept. 15–17). 

William Robinson, MD, the chief of vascular surgery at Southern Illinois University School of Medicine in Springfield, Illinois, was responding to a question from the floor of the gathering that called into question aspects of the study’s patient population. 

The research comes as recent trials report that NOACs, or direct oral anticoagulants (DOACs), alongside antiplatelet use, reduce limb and cardiovascular events when compared to antiplatelet therapy alone after infrainguinal surgical revascularization. Robinson, Syed Zaidi, MD— who delivered the findings at MVSS 2022—et al retrospectively analyzed patients in the Vascular Quality Initiative (VQI) who had undergone the bypass from 2014 until last year. 

Zaidi noted that rates of antiplatelet usage were “pretty steady” over the eight-year study period, whereas warfarin use “steadily decreased,” with NOAC administration “steadily increasing.” 

Univariate analysis showed that at one year, “the NOAC-plus-antiplatelet group had a statistically significantly reduced primary patency rate compared to antiplatelet alone.”Multivariate analysis demonstrated that NOAC use, prior bypass, diabetes and acute ischemic limb presentation “all were independently significant predictors of a reduced primary [and] primary assisted patency at one year.” Likewise, secondary patency rates showed a similar finding, Zaidi stated. 

Further, at 12 months, univariate analysis showed NOAC use associated with a lower major adverse limb event-free survival rate compared to the antiplatelet group. “We found several independent predictors on multivariate analysis— NOAC use, prior bypass, patient being non-ambulatory, rest pain or tissue loss and acute ischemic limb presentation—of increased major adverse limb events,” said Zaidi. 

NOAC use was also associated with reduced major amputation-free survival at one year, he continued, with multivariate analysis showing that non-ambulatory status, having an axillary bypass graft origin, tissue loss or acute ischemic limb presentation were associated with increased rates of major amputation. 

Univariate analysis demonstrated that overall survival in the NOAC group was 89% at one year compared to 91.3% in the antiplatelet group, Zaidi added. “We did find that warfarin ultimately had similar outcomes as NOAC therapy but, ultimately, did not include it in the final analysis due to its decreased usage over time,” he noted. 

“Combined antiplatelet and NOAC therapy after suprainguinal bypass was associated with worse limb outcomes and patency but equivalent statistically significant survival compared to antiplatelet therapy alone,” Zaidi concluded. “NOAC use in suprainguinal bypass has typically been extrapolated from infrainguinal data and can’t be recommended for routine use based on our experience. Additional prospective investigations are required to determine the role of NOACs and optimal antithrombotic therapy after suprainguinal bypass.” 

The questioner from the floor who noted some concern over the findings asked whether the study was dealing with equivalent patients. “I’m a little concerned that, if you publish this, you’re probably not comparing apples to apples; you’re going to give the recommendation that patients shouldn’t go on [rivaroxaban], or whatever,” he said. 

In response, Zaidi explained that the message was more “to be discriminating” about “who should get NOACs, [and] who shouldn’t.” 

Rising from the audience to explain further, senior author Robinson said he wanted to add some caveats. “We do know NOACs are being used a lot, and we don’t have a lot of data for their use. You bring up a lot of good points: Certainly, we can’t identify hypercoagulant states. Do we know every anatomic aspect of these patients in the VQI? No … 

“There is a fair bit of data you can control for, and I think using both propensity score matching and pretty aggressive multivariate analysis within that—you can’t do much better shy of a randomized trial is the bottom line. If you look at the randomized trials, we actually don’t have any of that information either.” 

Expanding on where the study might lead, Robinson added, “I do think [this study] adds a little bit, mostly being that it’s hypothesis-generating.” 


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