Increased Bleeding Without Benefit

The POPular PAUSE TAVI trial, presented at the European Society of Cardiology Congress 2024 and published in the New England Journal of Medicine, has challenged the conventional wisdom regarding the continuation of oral anticoagulation during transcatheter aortic valve replacement (TAVI).

The trial, conducted at 22 European sites, included 858 patients (mean age 81 years; 35% women) with an indication for oral anticoagulation who were undergoing TAVI. Investigators randomized them to periprocedural continuation or interruption of anticoagulation. Interruption occurred 48 to 120 hours before the procedure depending on the specific anticoagulant used, with treatment restarted after the procedure as soon as the operator or treating physician deemed it safe to do so.

The Findings

The results of the trial show that continuing oral anticoagulation during TAVI is associated with increased bleeding without any benefit in terms of reduced thromboembolic events. The rate of a primary composite outcome of cardiovascular (CV) death, stroke, myocardial infarction (MI), major vascular complications, or major bleeding in the first 30 days after the procedure was 16.5% among patients who kept taking their oral anticoagulants and 14.8% among those who temporarily interrupted treatment, a difference that failed to meet criteria for the noninferiority of the continuation strategy (P = 0.18).

While there were no differences in thromboembolic events between trial arms, bleeding—particularly minor bleeding—was more frequently observed with continuation of oral anticoagulation. Overall bleeding was more frequent with the continuation strategy (31.1% vs 21.3%; risk difference 9.8%; 95% CI 3.9%-15.6%).

What This Means for Clinical Practice

These findings have significant implications for clinical practice. The researchers acknowledge that the trial results are not applicable to patients undergoing TAVI via non-transfemoral access, and that the trial design had some limitations, such as the open-label design and insufficient statistical power for examining differences in the individual components of the primary outcome. However, the results suggest that interrupting oral anticoagulation before TAVI may be the safer approach for most patients.

The researchers state that the trial provides the first randomized data backing the interruption strategy, and that the findings are likely to impact guidelines and clinical practice. Dirk Jan van Ginkel, MD (St. Antonius Hospital, Nieuwegein, the Netherlands), who presented the results at the ESC Congress, said, “There was no advantage to continuing oral anticoagulation compared with interruption in patients undergoing TAVI with a need for anticoagulation.” Jurriën ten Berg, MD, PhD (St. Antonius Hospital), a senior investigator on the trial, added, “I think that this trial finally shows you that in general you have to interrupt in all those patients.”

Expert Opinion

Commenting on the findings for TCTMD, Santiago Garcia, MD (The Christ Hospital, Cincinnati, OH), said that he was not surprised by the results and that most interventional cardiologists would agree. He added that interruption of anticoagulation prior to TAVI “is what I would consider the standard of care in the US,” with treatment stopped 3 to 5 days before the procedure depending on the specific agent.

Garcia believes that the POPular PAUSE TAVI trial will strengthen guidelines on the management of anticoagulation during TAVI. While the trial results will likely not change practice significantly, since many physicians already interrupt anticoagulation before TAVI, he believes it provides a strong evidence base for the practice.

What About Exceptions?

Garcia notes that while the trial results suggest that interrupting anticoagulation is the safest approach for most patients, there may be a small number of patients who may benefit from continued anticoagulation. This may include patients with mechanical prostheses in other heart valves or those who have had a recent stroke. However, even in these cases, Garcia suggests stopping oral anticoagulation and considering bridging with heparin or low-molecular-weight heparin.

A Shift in Paradigm?

The POPular PAUSE TAVI trial has provided compelling evidence that interrupting oral anticoagulation before TAVI is the safer approach for most patients. This study is likely to have a significant impact on clinical practice and guidelines, potentially leading to a shift in the standard of care for patients undergoing TAVI. It is important to note, however, that there may be some exceptions, and the decision to continue or interrupt oral anticoagulation should be made on a case-by-case basis after careful consideration of the patient's individual risks and benefits.