Aspirin alone after transcatheter aortic valve implantation (TAVI) significantly reduced bleeding compared with aspirin plus clopidogrel, without increasing thromboembolic events, in the latest results from the POPular TAVI study.
“Physicians can easily and safely reduce rate of bleeding by omitting clopidogrel after TAVI,” lead author, Jorn Brouwer, MD, St Antonius Hospital, Nieuwegein, the Netherlands said.
“Aspirin alone should be used in patients undergoing TAVI who are not on oral anticoagulants and have not recently undergone coronary stenting,” he concluded.
Senior author, Jurriën ten Berg, MD, PhD, also from St Antonius Hospital, told theheart.org | Medscape Cardiology: “I think we can say for TAVI patents when it comes to antithrombotic therapy, less is definitely more.”
“This is a major change to clinical practice, with current guidelines recommending 3 to 6 months of dual antiplatelet therapy after a TAVI procedure,” he added. “We expected that these guidelines will change after our results.”
These latest results from POPular TAVI were presented at the virtual European Society of Cardiology (ESC) Congress 2020 and simultaneously published online in The New England Journal of Medicine.
The trial was conducted in two cohorts of patients undergoing TAVI. The results from cohort B — in patients who were already taking an anticoagulant for another indication — were reported earlier this year and showed no benefit of adding clopidogrel and an increase in bleeding. Now the current results in cohort A — patients undergoing TAVI who do not have an established indication for long-term anticoagulation — show similar results, with aspirin alone preferred over aspirin plus clopidogrel.
ten Berg explained that the recommendation for dual antiplatelet therapy (DAPT) was adopted mainly because this has been shown to be beneficial in patients undergoing percutaneous coronary intervention (PCI) with stenting; it was thought the same benefits would be seen in TAVI, which also uses a stent-based delivery system.
“However, TAVI patients are a different population — they are generally much older than PCI patients, with an average age of 80 plus and they have many more comorbidities, so they are much higher bleeding risk,” ten berg explained. “In addition, the catheters used for TAVI are larger than those used for PCI, forcing the femoral route to be employed and both of these factors increases bleeding risk.”
“We saw that in the trial, that patients on dual antiplatelet therapy had a much greater rate of major bleeding and the addition of clopidogrel did not reduce the risk of major thrombotic events,” such as stroke, myocardial infarction (MI), or cardiovascular (CV) death.
Given that the TAVI procedure is associated with an increase in stroke in the immediate few days after the procedure, it would seem logical that increased antiplatelet therapy would be beneficial in reducing this, ten Berg noted.
“But this is not what we are seeing,” he said. “The stroke incidence was similar in the two groups in POPular TAVI. This suggests that the strokes may not be platelet mediated. They might be caused by another mechanism, such as dislodgement of calcium from the valve or tissue from the aorta.”
For the current part of the study, 690 patients who were undergoing TAVI and did not have an indication for long-term anticoagulation were randomly assigned to receive aspirin alone or aspirin plus clopidogrel for 3 months.
The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non–procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non–procedure-related.
Results showed that a bleeding event occurred in 15.1% of patients receiving aspirin alone and 26.6% of those receiving aspirin plus clopidogrel (risk ratio, 0.57; P = .001).
Non–procedure-related bleeding occurred 15.1% of patients receiving aspirin alone vs 24.9% of those receiving aspirin plus clopidogrel (risk ratio, 0.61; P = .005).
Major, life-threatening, or disabling bleeding occurred in 5.1% of the aspirin-alone group vs 10.8% of those in the aspirin plus clopidogrel group.
Two secondary outcomes included thromboembolic events. The secondary composite 1 endpoint of death from cardiovascular causes, non–procedure-related bleeding, stroke, or MI at 1 year occurred in 23.0% of those receiving aspirin alone and in 31.1% of those receiving aspirin plus clopidogrel (difference, −8.2 percentage points; P for noninferiority < .001; risk ratio, 0.74; P for superiority = .04).
The secondary composite 2 endpoint of death from cardiovascular causes, ischemic stroke, or MI at 1 year occurred in 9.7% of the aspirin-alone group vs 9.9% of the dual antiplatelet group (difference, −0.2 percentage points; P for noninferiority = .004; risk ratio, 0.98; P for superiority = .93).
ten Berg pointed out that the trial was not strictly powered to look at thrombotic events, but he added: “There was no hint of an increase in the aspirin-alone group and there was quite a high event rate, so we should have seen something if it was there.”
The group has also performed a meta-analysis of these results, with some previous smaller studies also comparing aspirin and DAPT in TAVI which again showed no reduction in thrombotic events with dual antiplatelet therapy.
ten Berg noted that the trial included all-comer TAVI patients. “The overall risk was quite a low (STS score 2.5). This is a reflection of the typical TAVI patient we are seeing but I would say our results apply to patients of all risk.”
Simplifies and Clarifies
Discussant of the trial at the ESC Hotline session, Anna Sonia Petronio, MD, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, said, “This was an excellent and essential study that simplifies and clarifies aspects of TAVI treatment and needs to change the guidelines.”
“These results will have a large impact on clinical practice in this elderly population,” she said. But she added that more data are needed for younger patients and more complicated cases, such as valve-in-valve and bicuspid valves.
Commenting on the results for theheart.org | Medscape Cardiology, Robert Bonow, MD, Northwestern University, Chicago, Illinois, said, “The optimal anti-thrombotic management of patients undergoing TAVI who do not otherwise have an indication for anticoagulation (such as atrial fibrillation) has been uncertain and debatable. Aspirin plus clopidogrel for 3 to 6 months has been the standard, based on the experience with coronary stents.”
“Thus, the current results of cohort A of the POPular TAVI trial showing significant reduction in bleeding events with aspirin alone compared to DAPT for 3 months, with no difference in ischemic events, are important observations,” he said. “It is noteworthy that most of the bleeding events occurred in the first 30 days.
“This is a relatively small randomized trial, so whether these results will be practice-changing will depend on confirmation by additional studies, but it is reassuring to know that patients at higher risk for bleeding would appear to do well with low-dose aspirin alone after TAVI,” Bonow added.
“These results complete the circle in terms of antithrombotic therapy after TAVI,” commented Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, Texas.
“I would add two caveats: first is that most of the difference in the primary endpoint occurs in the first month and levels out between the groups after that,” Reardon said. “Second is that this does not address the issue of leaflet thickening and immobility.”
Ashish Pershad, MD, Banner – University Medicine Heart Institute, Phoenix, Arizona, added: “This trial answers a very important question and shows dual antiplatelet therapy is hazardous in TAVI patients. Clopidogrel is not needed.”
Pershad says he still wonders about patients who receive very small valves who may have a higher risk for valve-induced thrombosis. “While there were some of these patients in the trial, the numbers were small so we need more data on this group,” he commented.
“But for bread-and-butter TAVI, aspirin alone is the best choice, and the previous results showed for patients already taking oral anticoagulation, no additional antithrombotic therapy is required,” Pershad concluded. “This is a big deal and will change the way we treat patients.”
The POPular trial was supported by the Netherlands Organization for Health Research and Development. Brouwer reports no disclosures.
European Society of Cardiology (ESC) Congress 2020. Presented August 30, 2020.
N Engl J Med. Published online August 30, 2020. Abstract