TAVR and DAPT: Are We Any Closer to the Answer?

The antiplatelet medication of choice for patients undergoing transcatheter aortic valve replacement (TAVR) has been derived empirically. Periprocedural stroke and adverse cardiac events have been associated with worse outcomes at 30 days and 1 year after TAVR, with half of these events occurring after 24 hours. Dual antiplatelet therapy (DAPT), consisting of a thienopyridine and aspirin, improves clinical outcomes following coronary artery stenting through reductions in stent thrombosis and myocardial infarction. The mechanism of cardiac event rate reduction in coronary artery disease may be significantly different to that of TAVR. Platelet-mediated stent thrombosis, the antiproliferative effects of drug-eluting stents, and small caliber arteries are clearly a different milieu compared to TAVR procedures. The TAVR prosthesis has a greater metallic burden and greater flow turbulence across the valve, in coronary sinuses and paravalvular spaces, compared to drug-eluting coronary stents. The TAVR patient tends to be older and more likely to have peripheral vascular disease, and due to a higher rate of comorbidities, may have a higher risk of bleeding. The benefit of DAPT in coronary artery disease, weighed against the risk of bleeding, has been extrapolated to TAVR, without clear prior evidence to support this. The ACCF/AATS/SCAI/STS panel recommends DAPT with aspirin and clopidogrel after TAVR. The Canadian Cardiovascular Society recommends aspirin indefinitely and clopidogrel for 3 months in patients undergoing TAVR. Similarly to the duration of DAPT after coronary stenting, the necessary duration of clopidogrel remains unclear. In the meta-analysis by Abuzaid and colleagues (this issue), single antiplatelet therapy (SAPT) was compared to DAPT following TAVR. Previous meta-analyses on this subject have had variable conclusions, especially with regard to major bleeding complications. This analysis is the most current, comprehensive evaluation of this topic, comparing aspirin as SAPT versus dual antiplatelet therapy. The STS data registry is not included in this analysis due to a lack of clarity of SAPT as aspirin alone. Clinical trials that included anticoagulant therapy were also not included. There were 10 studies thatmet selection criteria with 2412 patients included. There were no differences in all-cause mortality, myocardial infarction or stroke, but the risk of major bleeding was greater with DAPT. The length of follow-up was approximately 6 months, which limits long-term conclusions. The increase in bleeding was driven largely by the observational studies rather than the randomized trials included in the meta-analysis. Major bleeding has been associated with an increase in overall mortality in randomized TAVR clinical trials. This publication contributes to a better understanding of necessary antiplatelet therapy, with more focus on safety. Several clinical scenarios require further clarification regarding DAPT strategies in TAVR patients, such as concomitant atrial fibrillation. As many as a third of extreme and high-risk TAVR patients have atrial fibrillation. Although many of these patients are already on anticoagulant therapy, there is an increased risk of cerebrovascular events in follow-up for 1 year after TAVR. As in PCI, adding antiplatelet therapy to existing anticoagulation increases bleeding risk. Anticoagulation with warfarin has been recommended (Class I, LOE B-NR) for stroke prevention in TAVR patients with atrial fibrillation, since the direct oral anticoagulants (apixaban, rivaroxaban, edoxaban or dabigatran) are not approved specifically for these patients. One such trial, Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes (GALILEO), should shed light on the efficacy and safety of rivaroxaban in TAVR patients who develop atrial fibrillation after the procedure. Determining the most appropriate anticoagulant and antiplatelet strategies is essential due to high clinical event rate and bleeding complication rate following development of atrial fibrillation on dual or triple therapy. Another clinical situation following TAVR is the development of leaflet thrombosis following TAVR. Thrombosis of valve leaflets may result in reduced leaflet motion, elevated valvular gradient and potentially decreased valve durability. Often computed tomography (CT) is necessary for confirmation of the diagnosis. The occurrence of leaflet thrombosis occurs more commonly in TAVR patients who received antiplatelet therapy compared to those on anticoagulation, although routine oral anticoagulation is not certain to prevent leaflet thrombosis. There may not be a difference in those taking warfarin compared to those on a direct oral anticoagulant. The treatment of leaflet thrombosis is anticoagulation, with no clear difference in efficacy between warfarin or direct oral anticoagulants. Leaflet thrombosis may also occur in patients who have received surgical bioprosthetic aortic valves. Guideline recommendations for anticoagulation following surgical bioprosthetic aortic valve replacement have been modified, with greater short-term use of anticoagulation with warfarin for 3–6 months after surgery. Moreover, a vitamin K antagonist for at least 3-months is also recommended (class IIa) after TAVR in patients at low risk for bleeding The incidence of leaflet thrombosis is being studied