DOACs May Have Advantage Over VKAs After TAVI, Study Hints

Among TAVI patients who have an indication for anticoagulation, direct oral anticoagulants (DOACs) appear to provide better outcomes than do vitamin K antagonists (VKAs), according to a French registry study.

Use of DOACs was associated with lower risks of all-cause mortality and major bleeding over 3 years of follow-up, with no significant differences in rates of acute coronary syndrome or ischemic or hemorrhagic stroke, researchers led by Romain Didier, MD, PhD (University Hospital of Brest, France), report.

The study, “to our knowledge, is the first long-term report, in a large real-life TAVR population, showing significant improvement in survival associated with reduced major bleeding rates with DOAC as compared to VKA,” Didier et al write.

They conclude that the analysis, published online today in JACC: Cardiovascular Interventions, “supports preferential use of DOAC rather than VKA in patients requiring oral anticoagulant therapy after TAVR,” adding, however, that the findings need to be confirmed in randomized trials.

But Daniele Giacoppo, MD (Alto Vicentino Hospital, Vicenza, Italy), who wrote an accompanying editorial, told TCTMD that it’s premature to give a preference for DOACs in the setting of TAVI, citing limitations inherent to observational studies reliant on administrative data.

“The study cannot provide definitive answers on this important question,” he said, although “the results of this registry suggest that there is no harm” related to using DOACs. That has been a concern, Giacoppo noted, ever since the results of GALILEO showed that DOAC-based therapy increased rates of death/thromboembolic events and serious bleeding compared with antiplatelet therapy in TAVI patients without an indication for oral anticoagulation.

For patients who require chronic anticoagulation after TAVI, however, these new findings suggest that DOACs are “a reasonable therapeutic choice,” Giacoppo said.

French TAVI Registries

The choice of oral anticoagulant in TAVI remains a hotly debated issue, and Didier et al note that US and European guidelines provide a preference for VKAs in patients who require anticoagulation for atrial fibrillation in the first 3 months after their procedure.

To explore which type of agent is better, the investigators examined data from two prospective, multicenter TAVI registries—France-TAVI and FRANCE 2—linked to administrative claims from the French national health insurance program. Of 24,581 patients who underwent TAVI between 2010 and 2017, 8,962 (36.5%) received oral anticoagulation. Of those, 2,180 (24.3%) were taking a DOAC and the rest were on a VKA.

Propensity score matching was used to adjust for differences, leaving 1,378 patients in the DOAC group and 1,093 in the VKA group. Overall, mean patient age was 83, and 52% were men. Most patients (70%) had atrial fibrillation. Concomitant use of antiplatelet therapy was common, with roughly 45% taking aspirin, 8% taking clopidogrel, and 10% taking both.

Through 3 years of follow-up, use of VKAs instead of DOACs was associated with greater risks of all-cause mortality and major bleeding (including hemorrhagic stroke), with no differences in other outcomes.

Outcomes at 3 Years After TAVI

The authors suggest that a reduction in major bleeding with DOACs could contribute to the lower rate of mortality.

“In AF patients, DOACs offer important safety advantages over VKAs because they are associated with lower rates of life-threatening and intracranial bleeding,” they write. “In addition, unlike randomized studies, including selected patients with strict monitoring of VKAs, real-life studies are conducted in unselected and often elderly patients with multiple comorbidities where compliance and adherence to therapeutic goals with VKAs may be more challenging to achieve, [and] as a result the bleeding risk with VKAs may be even greater than with DOACs.”

Don’t Change Guidelines Just Yet

Didier et al note that unless patients have other reasons to be taking oral anticoagulation, there is no evidence to support its use after TAVI.

For patients who require anticoagulation, the question of whether DOACs or VKAs are better remains open pending additional randomized data, Giacoppo said. The ATLANTIS trial showed that apixaban (Eliquis; Bristol-Myers Squibb) was not superior to standard of care—VKAs in those who required anticoagulation and antiplatelet therapy in those who didn’t—after TAVI. The ENVISAGE-TAVI AF trial, comparing a regimen based on edoxaban (Savaysa; Daiichi Sankyo) with VKA-based therapy, will provide additional insights.

As for now, the French registry data are “not sufficient to change guidelines or to establish a superiority of DOACs compared with vitamin K antagonists,” Giacoppo said.

But DOACs are a useful option, he said, particularly when considering the lack of evidence of any harm from DOACs—in ATLANTIS as well as in the registry data—and the practical advantages of the newer agents over VKAs. He pointed to the need for regular blood testing to monitor INR in patients on VKAs, which can be cumbersome for TAVI patients, who are generally older and frail and have a high comorbidity burden.

DOACs are “probably safer when a patient is very old, where you have concerns related to compliance, related to appropriate surveillance of the INR,” Giacoppo said. “I wouldn’t be afraid to use DOACs. I use DOACs in patients with TAVI. But I don’t expect a benefit in terms of efficacy.”