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Skipping the antiplatelet agent after transcatheter aortic valve replacement (TAVR, or TAVI) is safer for patients already on oral anticoagulation for other reasons, the POPular TAVI trial showed.

Bleeding of any kind occurred in 21.7% of patients randomized to oral anticoagulation alone compared with 34.6% of those assigned to oral anticoagulation plus 3 months of clopidogrel (Plavix, RR 0.63, 95% CI 0.43-0.90) over 12 months, Vincent Nijenhuis, MD, of St. Antonius Hospital in Nieuwegein, the Netherlands, at the virtual American College of Cardiology (ACC) meeting and simultaneously online in the.

The other primary endpoint of 12-month non-procedure-related bleeding -- defined as Bleeding Academic Research Consortium type 4 severe bleeding, which included most bleeding at the puncture site -- likewise favored oral anticoagulation alone (21.7% vs 34.0%, RR 0.64, 95% CI 0.44-0.92).

The net effect at 12 months still favored the single agent, with superiority met when combining cardiovascular death, non-procedure-related bleeding, stroke, and MI (31.2% vs 45.5%, RR 0.69, 95% CI for superiority 0.51 to 0.92) but noninferiority alone when looking the composite minus bleeding events.

Most bleeding events were at the TAVR access site, occurred in the first month, and were minor.

"These results support what many cardiologists have suspected, and provide some assistance in decision-making process for post-TAVR antiplatelet and anticoagulation regimens," commented Jonathan Schwartz, MD, of Sanger Heart & Vascular Institute in Charlotte, North Carolina. "While more data and larger trials are needed for definitive conclusions to be drawn, it is likely the rare exception that a patient will be discharged on both antiplatelet and DOAC therapy unless it is otherwise indicated."

Guidelines for antithrombotic treatment after TAVI in patients with indication for anticoagulation are based on expert opinion and suggest a vitamin K antagonist either alone or in combination with aspirin or clopidogrel, the researchers noted.

"The bigger picture is we're still unclear what to do with TAVR in someone without atrial fibrillation," in terms of antithrombotic regimens, said Robert Bonow, MD, of Northwestern University in Chicago and past president of the American Heart Association.

Triple therapy is out, and adding rivaroxaban (Xarelto) to antiplatelet therapy worsened outcomes after TAVR in the GALILEO trial, he noted, but "it's still uncertain what to do across the board in TAVI," he said.

POPular TAVI can't really resolve the issue even in patients with an indication for anticoagulation due to atrial fibrillation, cautioned Frederick Feit, MD, of NYU Langone Health in New York City, in an accompanying NEJM .

"Although there was no clear signal that withholding clopidogrel resulted in an increased risk of stroke, myocardial infarction, or death from cardiovascular causes, given the size of the trial and the wide noninferiority margins for estimates of differences between groups in these outcomes, that possibility has not been ruled out," he wrote.

Feit also noted "concerns regarding the classification of bleeding and the reliability of secondary outcome analyses. Bleeding occurring during TAVI or the index hospitalization was unadvisedly defined as non-procedure-related, even if it occurred at the access site."

Other problems were lack of data on baseline and procedural characteristics, including aspirin use and how often oral anticoagulants were held periprocedurally, lack of a placebo for clopidogrel, as well as that the assumption of proportional hazards for the two primary outcomes was not met.

Bonow agreed that the lack of standardization of periprocedural antithrombotic regimens was problematic, as it likely influenced the early bleeding that accounted for a large proportion of bleeds in the trial.

"If it's a patient on anticoagulation for atrial fibrillation, many times you can stop the anticoagulation for a couple days in relatively low risk individuals," he said. "It would be conceivable that you could reduce the bleeding in both groups if you were being more careful about handling the anticoagulation right before and during the procedure itself."

The open-label trial had two parts, this cohort B with an established indication for long-term oral anticoagulation and an ongoing cohort A among patients without an indication for long-term anticoagulation. Cohort B included 157 patients randomized to clopidogrel and 156 randomized to no clopidogrel for 3 months after undergoing TAVR, all who were on oral anticoagulation for appropriate indications.

Questioned at the late-breaking ACC clinical trial session about the reason for the early divergence in clinical outcomes outside of bleeding (13.4% vs 17.3%, RR 0.77 for cardiovascular death, MI, or ischemic stroke), Nijenhuis said the only possible explanation they found in looking at causes of death was that five of the 24 early deaths in the clopidogrel group were due to bleeding or vascular complication whereas none of these occurred in the oral anticoagulation alone group.

The ATLANTIS trial is underway comparing apixaban (Eliquis) with antiplatelet therapy in patients undergoing TAVR without an indication for anticoagulants and comparing it with vitamin K antagonists in those receiving anticoagulants.

"In the next couple of years we'll have a much better feel for standardization," Bonow told 名媛直播. "We're still not quite there yet."