alone after (TAVI) significantly reduced bleeding, compared with aspirin plus , 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, said in an interview: “I think we can say for TAVI patients, when it comes to antithrombotic therapy, less is definitely more.”
“This is a major change to clinical practice, with current guidelines recommending 3-6 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 Congress 2020 and simultaneouslyin 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 reportedand 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.
Dr. 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(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,” Dr. 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, 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,(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, Dr. 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 not 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 versus 10.8% of those in the aspirin plus clopidogrel group.
Two secondary outcomes included thromboembolic events. The secondary composite one 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 two endpoint of death from cardiovascular causes,, or MI at 1 year occurred in 9.7% of the aspirin-alone group versus 9.9% of the dual-antiplatelet group (difference, −0.2 percentage points; P for noninferiority = .004; risk ratio, 0.98; P for superiority = .93).
Dr. 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.
Dr. 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.”