Early Study Hints at Safety Edge With Apixaban in TAVR Patients With Atrial Fibrillation

Larry Hand

January 12, 2017

ULM, GERMANY — A new study shows patients with atrial fibrillation who undergo transcatheter aortic-valve replacement (TAVR) are at higher risk of adverse outcomes including death than patients in normal sinus rhythm. Further, AF patients were found to fare significantly better on a 30-day composite safety end point when treated with apixaban (Eliquis, Bristol-Myers Squibb) rather than a vitamin K antagonist (VKA)[[1].

"In patients undergoing TAVR, AF was associated with a significantly higher rate of all-cause mortality throughout 12 months of follow-up," senior investigator Dr Jochen Wöhrle (University of Ulm, Germany) told heartwire from Medscape. "The early safety end point in patients with AF on apixaban was significantly less frequent compared with patients receiving a VKA."

With prevalence of AF ranging from 32.9% to 46.8% in TAVR studies, the optimal oral anticoagulation regimen is an important issue. It is especially important to AF patients with elevated CHA2DS2-VASc scores, who carry high risk of thrombolic events.

Wöhrle and colleagues conducted a study with two aims: to assess the effect of AF on outcomes after TAVR and to assess the safety and efficacy of apixaban, a novel oral anticoagulant (NOAC), compared with a VKA in patients with AF after TAVR. They enrolled 617 patients, 345 (55.9%) in sinus rhythm and 272 (44.1%) with AF.

"This is the largest series using a NOAC for treatment of atrial-fibrillation in patients after TAVR so far," Wöhrle said. However, the researchers point out that "larger randomized controlled trials are needed to confirm these initial exploratory findings" based on single-center data.

The 30-day safety end point was a composite including all-cause mortality, major vascular complications, all stroke, life-threatening bleeding, acute kidney injury, coronary obstruction, major vascular complications, and valve dysfunction, according to the study, led by Dr Julia Seeger (University of Ulm) and published online January 2, 2017 in JACC: Cardiovascular Interventions.

They performed TAVR procedures using local anesthesia with patients under conscious sedation in a hybrid catheterization laboratory. They evaluated periprocedural, 30-day, and 12-month outcomes according to the Valve Academic Research Consortium-2 (VARC-2) criteria.

Patients in sinus rhythm had a mean age of 80.1, while patients with AF had a mean age of 81.3 (P=0.02).

The researchers found that patients with AF had higher risk for stroke and bleeding according to the CHA2DS2-VASc score (4.9, P=0.04) and the HAS-BLED score (3.1, P<0.01), plus a high risk of bleeding per HAS-BLED score of at least 3 (71.3% vs 47.8%; P<0.01).

They found the early safety end point at 30 days to be significantly more frequent in patients with AF (23.2% vs 11%; P<0.01), with patients with AF having more acute kidney injury (5.1% vs 1.4%; P <0.01) and life-threatening bleeding (4.4% vs 0.9%; P<0.01) at 30 days.

At 12 months, the composite of all-cause mortality and stroke was significantly higher for patients with AF compared with patients in sinus rhythm (21.7% vs 10.1%; P<0.01). Society of Thoracic Surgeon score for mortality and AF independently predicted all-cause mortality over 12 months of follow-up.

The rate of all stroke was similar between groups at 5.4% for patients with AF and 5.2% for patients in sinus rhythm.

Of the 272 patients with AF, 141 received apixaban treatment (2.3 mg twice daily) while 133 received the VKA phenprocoumon. Patients with AF on apixaban experienced a significantly lower rate of life-threatening bleeding (3.5% vs 5.3%; P<0.01). In addition, patients on apixaban experienced a significantly lower rate of stroke within 30 days (2.1% vs 5.3%).

In an accompanying editorial[2], Dr Lars Søndergaard and Dr Fadi J Sawaya (Copenhagen University Hospital, Denmark) write that the study adds to the ongoing debate about "what is the best and optimal antithrombotic regimen in patients post-TAVR, regardless of whether they are in sinus rhythm or with AF."

They note that oral anticoagulants have been associated with lower rates of structural valve deterioration after TAVR and that it seems that oral anticoagulation may protect against leaflet thrombosis or may even resolve it.

They write that several ongoing studies may help to answer that question. They described four studies ongoing in patients with sinus rhythm and three studies ongoing in patients with AF.

The largest sinus rhythm trial is the GALILEO trial, involving 1520 patients without AF, and comparing rivaroxaban (Xarelto, Bayer/Janssen) treatment with antiplatelet treatment in reducing thromboembolic events after TAVR.

The largest AF trial is the ATLANTIS trial, involving 1509 patients with and without AF, and comparing apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) with VKAs for the composite end point of death, MI, systemic emboli, intracardiac or bioprosthetic thrombus, or major bleeding.

They conclude, "A wealth of information will be uncovered from this potpourri of trials in the next few years, and one can foresee a change in the way we approach and manage patients after TAVR, both those with AF and those in sinus rhythm."

The study authors report no relevant financial relationships. Søndergaard has received research grants from Medtronic, St Jude Medical, Boston Scientific, Symetis, and Edwards Lifesciences and is a proctor for Medtronic, St Jude Medical, Boston Scientific, and Symetis. Sawaya reported no relevant financial relationships.

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