By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: The current clinical standard of dual antiplatelet therapy following transcatheter aortic valve replacement (TAVR) is controversial. The authors of the ARTE trial randomized post-TAVR patients to single or dual antiplatelet therapy and found that single antiplatelet therapy was associated with a lower risk of major bleeding events.
SOURCE: Rodés-Cabau J, Masson JB, Welsh RC, et al. Aspirin versus aspirin plus clopidogrel as antithrombotic treatment following transcatheter aortic valve replacement with a balloon-expandable valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) randomized clinical trial. JACC Cardiovasc Interv 2017 May 11. pii: S1936-8798(17)30812-9. doi: 10.1016/j.jcin.2017.04.014. [Epub ahead of print].
Current practice calls for between three and six months of dual antiplatelet therapy (DAPT) following transcatheter aortic valve replacement (TAVR). This recommendation has its origin in the major trials leading to TAVR approval in the United States (the PARTNER Trial and the CoreValve US Pivotal Trial). It is clear that the origin of this practice comes from expert opinion rather than from randomized trials. The traditional TAVR population includes primarily patients of advanced age and high frailty, with comorbidities that bring an elevated bleeding risk along with high surgical risk. In this group of patients, the use of higher intensity antiplatelet regimens may come with additional hazards beyond what we see in a surgery-eligible population.
The ARTE trial was a prospective, randomized, open-label clinical trial conducted at nine centers in Canada, Europe, and South America. A total of 222 patients presenting for TAVR with the Edwards balloon-expandable valve (initially the SAPIEN XT, and later the SAPIEN 3) were randomized 1:1 to receive either aspirin alone or aspirin plus clopidogrel following the TAVR procedure. Patients who had an indication for chronic anticoagulation were excluded, as were patients with recent drug-eluting stent implantation who already had an indication for DAPT. Patients with a recent history of serious bleeding or any history of intracranial hemorrhage, as well as patients with allergy to either drug, also were excluded. Patients were evaluated clinically at one month, three months, six months, and 12 months. The primary endpoint was the rate of death, myocardial infarction (MI), ischemic stroke or transient ischemic attack (TIA), or major bleeding at the three-month point.
To no one’s surprise, the aspirin alone group showed a trend toward lower occurrence of the primary endpoint (15.3% DAPT vs. 7.2% aspirin alone; P = 0.065), with non-significant trends in mortality (6.3% vs. 3.6%; P = 0.37), MI (3.6% vs. 0.9%; P = 0.18), and stroke or TIA (2.7 vs. 0.9%; P = 0.31). DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6%; P = 0.038).
The authors concluded that aspirin alone, when compared with DAPT, was associated with lower rates of major bleeding following TAVR without increasing the hazard for death or thrombotic complications, including MI and stroke.
COMMENTARY
The story of anticoagulant choice in routine TAVR patients is an interesting tale whose final chapters have yet to be written. Initial trials of TAVR were performed with DAPT after valve deployment, in part as a reflex equating the stent-mounted valve prostheses with other vascular stent implants.
Although there is no evidence to suggest that higher levels of antiplatelet activity (or of any antiplatelet activity at all) are important with TAVR valves, evidence has mounted in recent years that a significant percentage of such valves can be plagued by subclinical leaflet thrombosis (with as-yet-unclear clinical implications). In the recently-reported RESOLVE and SAVORY registries, approximately 15% of patients on antiplatelet therapy alone showed reduced leaflet motion suggesting thrombus, with no significant difference between dual and single antiplatelet therapy regarding this outcome. Anticoagulants, including warfarin and new oral anticoagulant drugs, reduced this frequency to approximately 3%.
Despite these data, guidelines continue to recommend DAPT as standard of care post-TAVR. ARTE is the latest in a string of modest-sized trials concluding that single antiplatelet therapy is not only as safe, but actually may be safer than DAPT in this population. At our center, we have little hesitation in simplifying the post-TAVR regimen to single antiplatelet therapy in patients who have thrombocytopenia or are otherwise at elevated risk of bleeding. Guidelines are unlikely to change until larger trials are published. POPular-TAVI and CLOE are examining similar questions with a cumulative total of thousands of patients planned. More interesting yet will be the forthcoming trials of anticoagulant vs. antiplatelet therapy post-TAVR, of which the AUREA (vitamin K antagonist), GALILEO (rivaroxaban), and ATLANTIS (apixaban) trials are the most widely anticipated.