A 68-year-old male presents to clinic complaining of shortness of breath and a recent episode of loss of consciousness with exertion. His past medical history is notable for chest irradiation to treat non-Hodgkin's lymphoma, hypertension, diabetes mellitus, stable coronary artery disease, and prostate cancer, as well as known aortic stenosis (AS). His electrocardiogram demonstrates sinus rhythm with left ventricular hypertrophy with strain. He undergoes a repeat echocardiogram, which demonstrates an aortic valve area of 0.7 cm2 (<1.0 cm2), with an elevated mean transvalvular gradient of 56 mm Hg. Coronary angiography shows non-obstructive epicardial disease. Given the severe symptomatic, high-gradient AS, he undergoes evaluation for intervention by members of the heart valve team who determine he is an appropriate candidate for transcatheter aortic valve replacement (TAVR). He successfully undergoes this procedure without complication.
The correct answer is: B. Aspirin indefinitely and clopidogrel for three to six months.
For high-risk surgical patients requiring aortic valve replacement (AVR), transcatheter aortic valve replacement, or TAVR, has become an increasingly important and efficacious option. However, patients who undergo TAVR are known to be at high risk for vascular complications in the first three months post-procedure. For example, the Placement of Aortic Transcatheter Valve (PARTNER) Trial, demonstrated an increased rate of stroke at 30 days in patients who had undergone TAVR as opposed to surgical AVR.1 Thus, the optimal antithrombotic strategy post-TAVR is an ongoing area of interest and research in the cardiology community.
The current standard of care, as recommended by the 2014 American Heart Association/American College of Cardiology guidelines, is aspirin indefinitely with clopidogrel for three to six months at clinician discretion (class IIb recommendation, level of evidence C), making choice B the best answer.2 This recommendation of dual antiplatelet therapy (DAPT) is derived, in part, from experience with percutaneous coronary intervention (PCI), considering similar transcatheter approaches, and the physiologic principal of allowing for prosthetic material incorporation and endothelialization post-procedure.
However, there is some data that compares single antiplatelet therapy with aspirin (choice A) to the DAPT standard of care (choice B). This data may suggest that single antiplatelet therapy is an equally efficacious option for preventing cardiovascular and cerebrovascular events, while being safer in regards to hemorrhage. Ussia et al., for example, randomized patients to lifelong aspirin versus lifelong aspirin and clopidogrel for three months post-TAVR.3 They showed no significant difference in the primary composite endpoint of major cardiac and cerebrovascular events at 30 days and six months. Similarly, Sabile et al. performed the Single Antiplatelet Therapy for TAVI (SAT-TAVI) trial, in which 120 patients were randomized post-TAVR to aspirin alone versus aspirin and clopidogrel.4 This study also showed no significant difference in adverse cardiovascular events between the two groups at 30 days, though noted a trend towards reduced risk of bleeding complications in the single antiplatelet therapy group. Finally, Aryal et al. performed a meta-analysis involving 640 patients undergoing TAVR, who received dual versus single antiplatelet therapy.5 This analysis showed a similar trend of no difference in the risk of stroke or myocardial infarction between groups and a higher risk of major bleeding in dual versus single antiplatelet therapy.
Collectively, these findings suggest that single antiplatelet therapy could be an acceptable option in selected patients who are intolerant of DAPT. However, given the limited number of patients studied so far, these findings need to be confirmed in a larger trial. To that end, the Aspirin versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation (ARTE) trial continues to compare these two strategies further.
Anticoagulation has also been considered as part of the antithrombotic strategy post-TAVR for several reasons. Firstly, there is an imperfect understanding of the nature of thromboembolic events post-TAVR, and whether they are primarily platelet-based or thrombin-based. In addition, patients who undergo TAVR may have concomitant indications for anticoagulation such as atrial fibrillation (AF) or venous thromboembolism (VTE). Finally, new-onset AF is relatively common following TAVR. For example, in a small series, 32% of patients who had not previously had atrial fibrillation developed new onset AF following TAVR.6
In these patients with co-morbidities requiring anticoagulation (e.g., AF or recent VTE), there is some experience post-TAVR with aspirin, clopidogrel, and oral anticoagulation, also known as "triple therapy" (answer option D). Zeymer et al. retrospectively compared outcomes of 1,450 patients in the German-TAVR registry, and found that at 30 days, patients on triple therapy did significantly worse than conventional strategy in a combined endpoint of death, stroke, embolism, and major bleeding.7
Given this experience, the current consensus guidelines suggest that in patients with concomitant AF, the decision can be made partially based on the strength of indication for DAPT, for example recent PCI. Thus, in patients with AF and recent PCI requiring DAPT, who also undergo TAVR, it is reasonable to pursue triple therapy. In patients with indications for anticoagulation (e.g., AF with CHA2DS2-VASc ≥2), in the absence of a strong indication for DAPT post-TAVR, it is reasonable to pursue aspirin alone with anticoagulation (answer option C).8
Currently, the Dual Antiplatelet Therapy Versus Oral Anticoagulation for a Short Time to Prevent Cerebral Embolism After TAVI (AUREA) Trial is ongoing to examine DAPT versus oral anticoagulation in the prevention of cerebral thromboembolism. The optimal management of antithrombotic strategies in various patient populations following TAVR remains an evolving field.
References
- Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98.
- Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive xummary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.
- Ussia GP, Scarabelli M, Mule M, et al. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol 2011;108:1772-6.
- Stabile et al. SAT-TAVI: A prospective, randomized trial of single vs. dual anti-platelet therapy after transcatheter aortic valve replacement in high-risk patients with aortic stenosis. In: Stabile ESG, Pucciarelli A, Cota L, et al (eds) Transcatheter cardiovascular therapeutics San Francisco, 2011.
- Aryal MR, Karmacharya P, Pandit A, et al. Dual versus single antiplatelet therapy in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis. Heart Lung Circ 2014 Jul 24. [Epub ahead of print]
- Amat-Santos IJ, Rodés-Cabau J, Urena M, et al. Incidence, predictive factors, and prognostic value of new-onset atrial fibrillation following transcatheter aortic valve implantation. J Am Coll Cardiol 2012;59:178-88.
- Zeymer U, Zahn R, Gerckens U, et al. Antithrombotic therapy after transfemoral aortic valve implantation (TAVI). Potential hazard of triple therapy. Eur Heart J 32(Suppl):900.
- Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.
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