Antithrombotic Cocktail Fails to Provide Benefit, Increases Bleeding in A-Fib Patients Undergoing TAVR

A new observational study of A-fib patients undergoing TAVR suggests that post-procedural triple therapy with a vitamin K antagonist (VKA) and antiplatelet therapy not only fails to provide a benefit but might be harmful to patients.

“The delicate balance between ischemic events and stroke prevention although concomitantly minimizing bleeding risk, remains an important yet unanswered clinical question following TAVR,” write Omar Abdul-Jawad Altisent, MD (Laval University, Quebec City, Canada), and colleagues, explaining their reasoning for conducting the study.

The researchers looked at 621 patients who underwent TAVR at 12 centers between 2007 and 2015. There were no differences in the rates of stroke, MACE, and death at a median follow up of 13 months among 101 patients who were prescribed monotherapy with a VKA and the 520 patients who received a VKA plus aspirin and/or clopidogrel.

In contrast, those on multiple antithrombotic therapy had a higher risk of major or life-threatening bleeding than patients who received monotherapy (24.4% vs 14.9%; HR 1.85; 95% CI 1.05-3.28). This relationship remained when the analysis was limited to only those on a VKA with or without a single antiplatelet agent.

“These findings suggest that prescribing an antiplatelet agent to [A-fib] patients already anticoagulated post-TAVR is unlikely to confer added clinical benefit while potentially being harmful,” the authors write.

The results were published in the August 22, 2016, issue of JACC: Cardiovascular Interventions.

Randomized Data Lacking

The issue of anticoagulation after TAVR is now coming to the forefront because “the field of TAVR has reached a level of maturity where procedural complications are decreasing tremendously and now we’re going to lower risk patients, so we’re focusing on how to improve mid-term and long-term outcomes,” Philippe Généreux, MD (Hôpital du Sacré-Coeur de Montréal, Canada), who was not involved with the study, told TCTMD.

The current pharmacology conundrum “is very similar to what we [saw] in coronary disease,” he said. But with TAVR, “there’s a big gap in the guidelines because there is no randomized trial assessing strategies with A-fib after TAVR,” Généreux continued, adding that the guidelines that do exist are “primitive and empirical.”

He predicted “an explosion of trials around this topic in the next 1 or 2 years that will help refine the guidelines.” That said, because of the complex nature of TAVR patients—as was similarly learned through the coronary disease experience—clinicians will have to be careful not to generalize the results of a single trial to the entire population and instead work on individualizing care, Généreux cautioned. “We’ll still need to use our clinical judgement at baseline and also at follow up to improve patient outcomes and not apply one recipe for all.”

For now, however, he said triple therapy should be avoided, or at least have its duration curtailed. “When you have an indication to give anticoagulation, maybe the takeaway is to avoid aspirin and give clopidogrel. That might be the best way to handle these patients.”

Guidelines Likely to Be ‘Overhauled’

Likewise, in an accompanying editorial, Thierry Lefèvre, MD (Institut Cardiovasculaire Paris Sud, Massy, France), writes that the findings “elicit broader considerations, beyond the problem of patients with [A-fib] who are eligible for TAVR.”

Firstly, based on the study outcomes, he advocates against prescribing antiplatelet therapy for A-fib patients already on long-term anticoagulation. The study also suggests that “if an oral anticoagulant must be combined with an antiplatelet treatment, it seems preferable to choose clopidogrel rather than aspirin,” Lefèvre said, consistent with findings from the WOEST study.

Finally, the study “indirectly raises the issue of short- or midterm anticoagulation therapy after TAVR for patients in sinus rhythm,” he writes.

Moving forward Lefèvre expects good news from studies of apixaban and dabigatran in TAVR patients with A-fib, as “the benefit ratio between efficacy and safety seems very favorable. In addition, their antithrombotic properties could prove interesting for patients with coronary artery disease, who account for 25% of TAVR patients.”

With this information and that to come, Lefèvre also expects current guidelines to be “completely overhauled within the next 2 to 3 years.”




  • Altisent O A-J, Durand E, Muñoz-García AJ, et al. Warfarin and antiplatelet therapy versus warfarin alone for treating patients with atrial fibrillation undergoing transcatheter aortic valve replacement. J Am Coll Cardiol Interv. 2016;9:1706-1717.
  • Lefèvre T. Anticoagulation treatment after transcatheter aortic valve replacement: striking the right balance. J Am Coll Cardiol Interv. 2016;9:1718-1720.


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  • Abdul-Jawad Altisent reports receiving support by a research PhD grant from the Alfonso Martin Escudero Foundation.
  • Lefèvre reports serving as a proctor for Edwards Lifesciences.
  • Généreux reports serving as a consultant and proctor for Edwards Lifesciences.