Long-term Mortality After TAVI Lower With DOACs vs VKAs

NEW YORK, NY—Patients undergoing TAVI who have an indication for oral anticoagulation are less likely to die over 5 years of follow-up if they’re discharged on a direct oral anticoagulant (DOAC) rather than a vitamin K antagonist (VKA), a retrospective study suggests.

Although there was no significant difference in all-cause mortality between the DOAC and VKA groups at 1 year, a significant difference had emerged by 3 years and widened by 5 years, Agam Bansal, MD (Cleveland Clinic, OH), reported here at New York Valves 2024, previously known as the TVT meeting.

He speculated that the poorer outcomes among patients on VKAs over the long term could be related to the higher rates of major bleeding, which predisposes them to increased mortality, in that group.

Whatever the reason, the study—the largest observational analysis to compare the safety and effectiveness of DOACs versus VKAs after TAVI, and the only one to track outcomes out to 5 years—"clearly demonstrates DOACs are associated with improved long-term outcomes with reduction in all-cause mortality and major bleeding,” Bansal said.

However, a major limitation of the analysis—one acknowledged by Bansal—is that the investigators couldn’t determine which patients had a mechanical valve (eg, a prior failed surgical aortic valve or a mechanical mitral bioprosthetic), commented James Stewart, MD (Piedmont Healthcare, Atlanta, GA). VKAs are the anticoagulants of choice in patients with mechanical heart valves due to trials demonstrating harm with DOACs.

“I suspect in this day and age the people that were persistently on vitamin K antagonists long term were probably mechanical valve patients,” he told TCTMD. “That’s just inherently a group with higher bleeding risk, higher risk for long-term complications, and I wonder how much that affected their 3- and 5-year results.”

Conflicting Results in the Literature

Bansal pointed out that the results of prior studies examining choice of oral anticoagulant after TAVI—specifically in patients with an indication for one, which encompasses about half of those undergoing the procedure—have been mixed. The ATLANTIS trial showed that clinical outcomes and bleeding rates were similar with apixaban (Eliquis; Bristol Myers Squibb) and VKAs, whereas the ENVISAGE-TAVI AF trial demonstrated similar clinical outcomes with edoxaban (Savaysa; Daiichi Sankyo) and VKAs, but more major bleeding with the DOAC.

In contrast, patients included in the OCEAN-TAVI registry who were treated with a DOAC versus a VKA had a significantly lower risk of all-cause mortality, with no difference in bleeding.

To explore this issue further, Bansal and colleagues examined data from the TriNetX Research Network, which has access to information on more than 85 million patients treated within 90 healthcare organizations, mostly in the United States. Their analysis included 13,189 patients who underwent transfemoral TAVI between 2015 and 2023 and were discharged on oral anticoagulation, mostly for atrial fibrillation (82.6%) and venous thromboembolism (11.4%).

About two-thirds of patients received a DOAC—apixaban in 82.4% and rivaroxaban (Xarelto; Bayer/Janssen) in the rest—with the remaining one-third taking a VKA.

After propensity-score matching, there were 4,815 pairs of patients taking either a DOAC or a VKA (mean age 79 years; 39% women).

At 1 year of follow-up, there were no significant differences between the DOAC- and VKA-treated patients in terms of all-cause mortality (10.7% vs 12.0%; P = 0.065), stroke/TIA (2.2% vs 1.8%; P = 0.192), and major bleeding requiring transfusion (5.4% vs 6.2%; P = 0.132), although there was less intraprocedural bleeding in the DOAC group (1.2% vs 2.4%; P < 0.001).

The findings regarding stroke/TIA and intraprocedural bleeding remained consistent through 5 years, but significant differences favoring DOACs over VKAs emerged at 3 years for all-cause mortality (19.1% vs 25.8%; P < 0.001) and major bleeding (7.1% vs 8.7%; P = 0.009). By 5 years, the advantage for DOACs had grown for both of those outcomes:

• All-cause mortality (22.5% vs 33.9%; P < 0.001)
• Major bleeding (7.7% vs 9.5%; P = 0.002)

Mortality and bleeding outcomes were similar when comparing apixaban and rivaroxaban.

DOACs Taking Over

The investigators also showed that use of DOACs increased significantly during the study period (P < 0.001), while use of VKAs declined. And Bansal asked hypothetically whether patients with an indication for oral anticoagulation after TAVI should be switching from VKAs to DOACs.

“It appears, with the limitations of retrospective data, that actually the DOACs may show a [survival] benefit with reduced bleeding, reduced procedural bleeding,” Stewart said.

And he pointed out that the larger trend toward use of DOACs after TAVI seen in the study fits with what he’s observed. “For ease of use, a lot of us are kind of encouraging patients to switch to DOACs anyway,” he said.

Bansal acknowledged some limitations of the analysis, including the possibility of residual confounding due to the observational design. In addition, aside from not having information on which patients had mechanical valves, the investigators didn’t account for concomitant antiplatelet therapy and looked at only two of the DOACs.