POPular-TAVI: Concomitant Antiplatelet Use Increases Bleeding Risk

Vincent Nijenhuis, MD

Results of Patients undergoing Transcatheter Aortic Valve Implantation (POPular-TAVI) indicate oral anticoagulation monotherapy significantly reduces bleeding and is non-inferior in reducing clotting-related complications in patients with a long-term need for anticoagulation after TAVI compared to concomitant oral anticoagulation with clopidogrel.

The first randomized trial assessing the use of oral anticoagulant monotherapy versus oral anticoagulants with antiplatelet therapy, results of POPular-TAVI, which was presented at the American College of Cardiology’s Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC), have the potential to be practice-changing—with results reflecting a 43% reduction in bleeding complications with the use of oral anticoagulants without clopidogrel.

“This study helps physicians to better understand the risks of adding antiplatelet therapy to oral anticoagulants—namely, that doing so leads to more bleeding without reducing the rate of ischemic events,” said lead investigator Vincent Nijenhuis, MD, from the cardiology department at St. Antonius Hospital in Nieuwegein, Netherlands, in a statement. “I think once physicians are aware of this, they will not treat patients undergoing TAVR so aggressively, leading to better outcomes.”

The randomized, open-label trial assigned patients from 17 sites across Europe in a 1:1 ratio to anticoagulation therapy with or without clopidogrel for 3 months. Investigators of the trials assessed 2 primary outcomes—all bleeding and non-procedure-related bleeding over at least 1 year of follow-up. A pair of secondary outcomes included a composite of cardiovascular (CV) death, non-procedure-related bleeding, stroke, or myocardial infarction (MI) and a composite of CV death, ischemic stroke, or MI—secondary outcomes were tested for noninferiority at 12 months, with a noninferiority margin of 7.5 percentage points for the absolute difference.

A total of 326 patients underwent randomization, of which 157 were eligible for analysis in the monotherapy group and 156 were eligible among those randomized to concomitant clopidogrel.

Bleeding occurred in 34 (21.7%) patients receiving oral anticoagulation monotherapy compared to 54 (34.6%) patients receiving concomitant clopidogrel (HR, 0.63; 95% CI, 0.43-0.90; P=.01). Non-procedure-related bleeding occurred in 34 (21.7%) patients receiving monotherapy versus 53 (34.0%) patients receiving concomitant clopidogrel (HR, 0.57; 95% CI, 0.37-0.88; P=.010). Investigators noted most bleeding occurred in the first month and was minor.

The composite endpoint of CV death, non-procedure-related bleeding, stroke, or MI occurred in 49 (31.2%) patients receiving monotherapy and in 71 (45.5%) patients receiving concomitant clopidogrel (difference -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; RR, 0.69; 95% CI for superiority, 0.51-0.92). The other composite secondary endpoint occurred in 21 (13.4%) patients receiving oral anticoagulant monotherapy versus 27 (17.3%) patients receiving concomitant clopidogrel (difference, −3.9 percentage points; 95% CI for noninferiority, −11.9 to 4.0; RR, 0.77; 95% CI for superiority, 0.46-1.31).

“The results suggest it would be beneficial to not give clopidogrel—in fact, it’s safer because it does not lead to as many bleeding events,” Nijenhuis said in the aforementioned statement.

This study, “Antithrombotic Therapy After Transcatheter Aortic Valve Implantation In Patients With A Long-term Indication For Oral Anticoagulation (POPular TAVI Trial - Cohort B),” was presented at ACC.20/WCC.