Update to Chapter 47: Aortic Valve Disease

Study Summary

The POPular TAVI cohort A trial was a randomized, open-label, controlled trial comparing single and dual antiplatelet therapy in patients following transcatheter aortic valve implantation (TAVI) who did not have an indication for long-term anticoagulation. The study randomized 690 patients in a 1:1 fashion prior to TAVI to either aspirin alone or aspirin and clopidogrel for 3 months following the procedure. At 12 months, compared to aspirin and clopidogrel, aspirin monotherapy resulted in a significantly lower incidence of bleeding from all causes (15.1% versus 26.6%; RR 0.57, 95% CI 0.42-0.77, P = 0.001; see accompanying Hurst's Central Illustration) as well as non-procedural bleeding (15.1% versus 24.9%; RR 0.61, 95% CI 0.44-0.83, P = 0.005), which included TAVI access site bleeding. The majority of bleeding events occurred in hospital and were related to access site issues. Among secondary outcomes, aspirin alone was also shown to be non-inferior to aspirin and clopidogrel for the composite of thromboembolic events, including death from cardiovascular causes, ischemic stroke, and myocardial infarction (9.7% versus 9.9%; P = 0.004).

Commentary

Study Strengths: The study was carried out across 17 sites in Europe and randomized patients in a balanced fashion in regards to age, gender, TAVI indications, and underlying cardiac co-morbidities. Notably, no patients were lost to follow-up, enabling complete data collection for both primary and secondary outcomes.

Study Limitations: The open-label design of this trial was a limiting factor, though this was tempered by an adjudication committee blinded to the trial-group assignments. The study was powered for a composite of bleeding and thromboembolic events rather than thromboembolic events alone. Additionally, the investigators utilized the BARC type 4 classification to define procedure-related bleeding, which was not designed for the TAVI population and included a narrow range of bleeding scenarios. TAVI access site bleeding, which comprised the majority of bleeding complications, was categorized under non-procedure related bleeding.

Next Steps/Clinical Perspective: The results of POPular TAVI suggest that patients who are not on anticoagulation and without recent coronary stenting who undergo TAVI could be placed on aspirin alone with a lower overall risk of bleeding and without a significant increase in thromboembolic events compared to a dual antiplatelet strategy. As antiplatelet therapy was initiated prior to TAVI, peri-procedural and in-hospital bleeding events accounted for the predominant difference between the two treatment groups, evidenced by a rapid flattening of event curves in both groups. Dual antiplatelet therapy with aspirin and clopidogrel was only continued for 3 months, so the two groups were medically managed the same way from months 4 to 12. The increased signal in ischemic events in secondary outcomes in the aspirin monotherapy arm beyond 6 months warrants further evaluation. Following these patients beyond the 12-month mark and replicating this study at other centers may yield additional insights in governing the proper antiplatelet regimen and its duration following TAVI. Finally, medium and long-term durability of the valves were not assessed in this trial.

Trial Reference