Aspirin Alone Better for Post-TAVI Patients not on Anticoagulation: POPular TAVI
Study comparing aspirin+clopidogrel vs. aspirin shows aspirin alone reduced risk of all bleeding with no increased thrombotic risk for post-TAVI patients not on oral anticoagulation
Aspirin alone is better than the dual antiplatelet therapy with aspirin and clopidogrel for patients undergoing transcatheter aortic valve implantation (TAVI) not on oral anticoagulation and without recent coronary stenting, POPular TAVI findings showed.
The study results, presented at the European Society of Cardiology Congress 2020 (ESC 2020), showed aspirin alone compared to an aspirin+clopidogrel combo after TAVI significantly cut bleeding risk more without increasing the risk of thrombotic events.
¡°Aspirin alone compared to aspirin with clopidogrel reduced the bleeding rate significantly, with an absolute reduction of more than 10 percent,¡± POPular TAVI coordinating investigator Jorn Brouwer, MD (St. Antonius Hospital, Netherlands) said. ¡°At the same time, aspirin alone versus aspirin with clopidogrel did not increase thromboembolic events as captured in the secondary outcomes.¡±
The findings have challenged current European guideline recommendations on antiplatelet treatment and is expected to impact future updates. The European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) had recommended a three- to six-month aspirin and clopidogrel therapy for initial antiplatelet treatment followed by aspirin or clopidogrel monotherapy since 2012.
Despite current recommendations, explorative studies have shown that adding clopidogrel to aspirin is linked with a higher rate of major bleeding without a decreased risk of thromboembolic complications. The evidence for aspirin alone has also been lacking: only small-scale studies have suggested that aspirin alone could be effective for the patient group.
Against this backdrop, the two-cohort POPular TAVI trial sought to address the best therapy to counter the relatively high risks of bleeding and ischaemic complications after TAVI that are associated with increased mortality.
Results from POPular TAVI¡¯s cohort A were presented at ESC 2020 on Aug. 30 and simultaneously published in the New England Journal of Medicine (NEJM)1.
Findings simplify, outline antithrombotic therapy after TAVI
Cohort A of POPular TAVI studied patients not on chronic oral anticoagulation while cohort B looked at patients on chronic anticoagulation.
Cohort B results - presented at the American College of Cardiology¡¯s annual conference (ACC 2020) last March and simultaneously published in the NEJM2 - showed anticoagulant treatment without clopidogrel reduced the risk of bleeding without increasing thrombotic events.
Both cohorts were powered separately for study outcomes, investigators said.
The study findings recently presented at ESC 2020 pertain to that of cohort A. Cohort A originally recruited 690 patients from the Netherlands, Belgium, Luxembourg, and the Czech Republic who were not indicated for oral anticoagulation. Investigators then excluded patients who had undergone coronary artery stenting using a drug-eluting stent within three months or a bare-metal stent within one month before TAVI, leaving a total of 665 patients in the cohort.
Investigators randomly allocated the 665 patients not indicated for oral anticoagulation to take either aspirin alone (331 patients) or aspirin with clopidogrel for three months (334 patients) after undergoing TAVI. Patients in both arms were 80 years old on average.
The primary endpoint was designed to test the potential superiority of aspirin alone. To see whether aspirin alone compared to aspirin+clopidogrel for three months would reduce the rate of bleeding at one year, co-primary endpoints were defined as 1) all bleeding including non-major, major, and life-threatening bleeds (procedural and non-procedural) and 2) non-procedural bleeding.
Also tested was the hypothesis that aspirin alone would be non-inferior to aspirin+clopidgorel with respect to two secondary endpoints at one year, defined as 1) a composite of cardiovascular mortality, non-procedural bleeding, all-cause stroke, or myocardial infarction (bleeding and thromboembolic events) and 2) a combination of cardiovascular mortality, ischaemic stroke, or myocardial infarction (only thromboembolic events).
Results showed that aspirin alone resulted in a significantly lower incidence of bleeding compared to aspirin+clopidogrel at one year. All bleeding occurred in about 15 percent of the aspirin monotherapy group and 27 percent in the aspirin+clopidogrel group, indicating a 45 percent lower risk of all bleeding (RR 0.57, 95% CI 0.42-0.77, p=0.001). Non-procedural bleeding occurred in 15 percent versus 25 percent of the aspirin monotherapy and combination therapy groups, respectively (RR 0.61, 0.44-0.83, p=0.005).
For the secondary outcome on bleeding and thromboembolic events, aspirin alone proved both non-inferiority and superiority compared to the aspirin+clopidogrel combination. The outcome occurred in 23 percent in patients receiving aspirin alone compared to 31 percent receiving aspirin+clopidogrel (difference -8.2%p, 95% CI for noninferiority -14.9 to -1.5, p<0.001; RR 0.74; 95% CI for superiority 0.57–0.95; p=0.04).
The secondary outcome regarding thromboembolic events occurred in 9.7 percent of patients receiving aspirin alone compared to 9.9 percent receiving aspirin+clopidogrel (difference -0.2%p, 95% CI for noninferiority -4.7 to 4.3; p=0.004).
¡°Aspirin alone significantly lowered the risk of bleeding and does not increase the risk of thrombotic events, indicating that removing clopidogrel after TAVI can easily and safely reduce the risk of bleeding,¡± Brouwer said. ¡°The trial shows that aspirin alone should be used in patients undergoing TAVI who are not on oral anticoagulation and have not recently undergone coronary stenting,¡±
Commenting on study findings at ESC 2020, Anna Sonia Petronio, MD (Azienda Ospedaliero-Universitaria Pisana, Italy) noted that,
Findings from the trial simplified and clearly outlined antithrombotic therapy after TAVI and calls for a change in future guidelines. These results will greatly impact how we treat elderly patients in the clinical setting and further studies should focus on younger patients or complex cases such as valve-in-valve procedures or bicuspid valves.
- Nijenhuis VJ, Brouwer J, Delewi R, et al. Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020;382:1696–1707.