POPular TAVI compared this strategy to oral anticoagulation plus clopidogrel for 3 months after TAVR
Patients with atrial fibrillation on oral anticoagulation (OAC) therapy who underwent transcatheter aortic valve replacement (TAVR) and continued treatment with OAC alone had a lower rate of serious bleeding at 1-year follow-up than patients who received OAC plus clopidogrel for 3 months after TAVR, according to late-breaking trial results presented Sunday at the American College of Cardiology Scientific Sessions 2020 virtual conference.
Jurrien ten Berg, MD, PhD, MSc, of St. Antonius Hospital, Nieuwegein, Netherlands, presented the results of Cohort B of the POPular TAVI trial. This study was simultaneously published online in The New England Journal of Medicine.
A significant percentage of patients undergoing TAVR, also known as transcatheter aortic valve implantation (TAVI), have concomitant atrial fibrillation requiring them to be on chronic OAC. Current guidelines do not specify a treatment strategy for these patients after TAVR, and the question of whether the addition of an antiplatelet to treatment with OAC is beneficial is not yet understood.
POPular TAVI is a prospective, randomized, parallel-group, open-label, multi-center trial performed at 17 European sites. It has two cohorts. Cohort A randomized patients without an indication for OAC after TAVR to aspirin or aspirin and clopidogrel. Cohort B, which was presented Sunday, randomized patients on chronic OAC therapy to treatment with OAC alone or to clopidogrel for three months in addition to OAC after TAVR.
The main inclusion criteria included the need for long-term OAC, and the main exclusion criteria were drug-eluting stent implantation 3 months before TAVR, bare metal stent implantation 1 month pre-TAVR or clopidogrel allergy. Randomization was performed before TAVR in a 1:1 ratio.
The trial had two primary outcomes: all bleeding and non-procedural bleeding. The Valve Academic Research Consortium-2 (VARC-2) was used to classify bleeding events and vascular complications, and Bleeding Academic Research Consortium (BARC) type 4 severe bleeding was used to define procedure-related events.
A total of 326 patients underwent randomization; 164 were assigned to receive OAC alone, and of those patients, 157 completed 12 months of follow-up. In the second arm, 162 were assigned to receive OAC plus clopidogrel for 3 months, of whom 156 patients completed 12 months of follow-up. There were no significant differences between the groups in baseline characteristics. The patients’ mean age was approximately 81 years, and about 45.4% were women.
Patients who received OAC alone were less likely to experience all-cause bleeding than those taking OAC and clopidogrel (21.7% vs. 34.6%; risk [RR], 0.63; 95% confidence interval [CI], 0.43-0.90; p = 0.01). Access-site bleeding was the most common cause of bleeding.
One secondary composite outcome (cardiovascular-related death, non-procedure-related bleeding, all-cause stroke, or myocardial infarction) occurred in 31.2% of the OAC-alone group and in 45.5% of the OAC-plus-clopidogrel group (95% CI for noninferiority, −25.0 to −3.6; RR, 0.69; 95% CI for superiority, 0.51 to 0.92). Another secondary composite outcome (cardiovascular-related death, ischemic stroke, or myocardial infarction) occurred in 13.4% receiving OAC alone and in 17.3% receiving OAC plus clopidogrel (95% CI for noninferiority, −11.9 to 4.0; RR, 0.77; 95% CI for superiority, 0.46 to 1.31). Both of these outcomes showed noninferiority for OAC alone, but the authors wrote in the New England Journal of Medicine manuscript, “No clinical inferences can be drawn for these secondary outcome results because of the lack of a plan for correction for multiple comparisons.”
“The rates of complications for TAVR — especially complications related to bleeding — remain high,” said Vincent Nijenhuis, MD, of St. Antonius Hospital and the study’s lead author, in a news release accompanying the trial results. “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. I think once physicians are aware of this, they will not treat patients undergoing TAVR so aggressively, leading to better outcomes.”
The trial was funded by The Netherlands Organization for Health Research and Development.