A comprehensive meta-analysis and real-world registry data provide compelling evidence that single antiplatelet therapy (SAPT) offers superior safety outcomes compared to alternative antithrombotic strategies following transcatheter aortic valve replacement (TAVR). The findings challenge previous assumptions about optimal post-procedural management and reinforce current clinical guidelines.
Meta-Analysis Reveals Bleeding Risk Reduction
A systematic review and meta-analysis of seven randomized controlled trials involving 3,164 patients compared various antithrombotic regimens after TAVR. The study, which included 602 patients receiving dual antiplatelet therapy (DAPT), 1,052 receiving direct oral anticoagulants (DOACs), 1,463 receiving SAPT, and 44 receiving vitamin K antagonist plus SAPT, demonstrated significant safety advantages for SAPT.
Patients receiving SAPT showed significantly lower rates of major bleeding and life-threatening bleeding compared to those treated with DOACs (OR: 0.68; 95% CI: 0.47-0.99). No significant differences were observed in all-cause mortality, cardiovascular mortality, or minor bleeding events between the treatment groups.
The analysis found no significant differences in efficacy endpoints, including ischemic stroke/transient ischemic attack, systemic embolism, hypoattenuated leaflet thickening (HALT), or reduced leaflet motion (RELM) events when comparing SAPT to DOACs.
Real-World Registry Confirms Mortality Benefits
Complementing the meta-analysis findings, data from the multicenter Transfusion Requirements in Transcatheter Aortic Valve Implantation (TRITAVI) registry analyzed 5,514 patients (mean age 81.5±6.8 years, 48.4% male) discharged on either SAPT (n=3,197) or DAPT (n=2,317).
The registry data revealed striking differences in clinical outcomes at six months. All-cause mortality was significantly lower in the SAPT group compared to the DAPT group (2.4% vs 5.4%), as was the rate of major bleeding (0.5% vs 1.3%). SAPT demonstrated advantages in both cardiovascular mortality (1.3% vs 2.2%) and non-cardiovascular mortality (1.1% vs 3.2%) compared to DAPT.
"We were surprised to find that SAPT, rather than DAPT, after TAVR is associated with a better outcome, even in patients with CAD," said Francesco Pelliccia, MD, PhD, Associate Professor of Cardiology at Sapienza University in Rome, Italy, and lead author of the TRITAVI study.
Consistent Benefits Across Patient Populations
Sensitivity analyses from the TRITAVI registry confirmed that DAPT was significantly associated with increased mortality risk across diverse patient populations. The association held true for both men (adjusted HR: 2.08; 95% CI: 1.32-3.30) and women (adjusted HR: 1.53; 95% CI: 1.03-2.29), as well as in patients with coronary artery disease (adjusted HR: 1.83; 95% CI: 1.01-3.35) and those without coronary artery disease (adjusted HR: 1.52; 95% CI: 1.04-2.20).
Clinical Implications and Guidelines Alignment
The findings support current recommendations from the American College of Cardiology (ACC) and American Heart Association (AHA), which advocate for SAPT after TAVR in patients without indications for oral anticoagulation. The 2020 guidelines recommended this approach based on the principle of balancing thrombotic prevention with bleeding risk minimization.
The meta-analysis authors noted that the basic principle of antithrombotic therapy after TAVR involves balancing the prevention of leaflet thrombosis with bleeding risk. Given that most TAVR recipients are elderly with multiple comorbidities, tailoring treatment to individual anticoagulation needs remains crucial for optimizing both bleeding and thromboembolic risk profiles.
Subclinical Valve Thrombosis Considerations
While DOACs have been shown to reduce imaging biomarkers associated with subclinical valve thrombosis, including HALT and RELM, current randomized controlled trials have not demonstrated conclusive evidence that DOACs improve long-term valve durability or hemodynamic performance. The GALILEO trial, for instance, showed a reduction in HALT and RELM with rivaroxaban compared to antiplatelet therapy, but no significant difference in clinical valve dysfunction endpoints was observed.
The impact of subclinical leaflet thrombosis on clinical outcomes after TAVR remains unclear, with some reports suggesting it may not be a decisive factor in evaluating different antithrombotic methods. Future randomized controlled studies are needed to clarify the relationship between stroke or transient ischemic attack and valvular thrombosis.
Study Limitations and Future Directions
The meta-analysis authors acknowledged several limitations, including the heterogeneity among studies and the inclusion of some anticoagulated patients in one trial subgroup. The varied timing, usage, dosage, valve types, and patient risk levels related to antithrombotic strategies across studies also limit generalizability.
Despite these limitations, both studies provide robust evidence supporting SAPT as the optimal antithrombotic strategy for patients without anticoagulation indications following TAVR. The findings offer clinicians clearer guidance for managing high-risk bleeding patients and reinforce the evidence base for current standard-of-care recommendations.
