In this observational study of antithrombotic therapies after TAVR we found that a strategy of routine anticoagulation is feasible in the majority of patients (88%), and associated with similar risk of bleeding and cerebral ischemic events relative to antiplatelet therapy alone.
The optimal antithrombotic therapy after TAVR remains controversial and a subject of intense investigation . Dual antiplatelet therapy has been used in the pivotal trials that led the Food and Drug Administration (FDA) to approve transcatheter valves for clinical use and subsequently adopted as the “default” strategy in clinical practice given absence of randomized clinical trial data. The concerns raised by Makkar et al. regarding the presence of subclinical leaflet thrombosis on surgical and transcatheter bioprosthetic aortic valves prompted a reexamination of what constitutes optimal antithrombotic regimen after TAVR . A recently published trial comparing single versus double antiplatelet therapy after TAVR (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation or ARTE) showed that single therapy reduces the incidence of major or life-threatening bleeding without increasing the risk of ischemic events .
An ideal antithrombotic strategy should reduce clinically relevant end-points during the period in which these events are more likely to occur while having an acceptable side-effect (bleeding) profile. Heras et al. found that the risk of thromboembolism after surgical bioprosthetic valve implantation decreases significantly at each time interval after the operation (day 1–10: 41%/year, day 11–90: 3.6%/year, and > 90 days 1.9%/year, p < 0.01) . The same authors found that the risk of thromboembolism was higher among patients who were not taking anticoagulants . Data from the Danish National Patient Registry confirmed the first 3–6 months after surgery as the period where thromboembolic events are more likely to occur . Similarly, patients treated with warfarin for 6 months in this large registry had reduced thromboembolic events and cardiovascular death . Based on these two observational studies, the 2017 American Heart Association (AHA)/American College of Cardiology (ACC) focused update of the guideline for the management of patients with valvular heart disease gave anticoagulation with a vitamin K antagonist (VKA) for at least 3 months, and perhaps 6 months, a Class IIa (reasonable) recommendation after SAVR and a class IIb recommendation after TAVR . Our study results support this new recommendation. Although long-term anticoagulation can increase the risk of bleeding in the elderly we found that a brief treatment, which targets the period in which thromboembolic events are more likely to occur, was well tolerated. The bleeding profile of the anticoagulation regimen used in our study was similar to antiplatelet therapy.
The proportion of therapeutic INRs (between 2.0 and 3.0) relative to the total number of INRs measured was 43% (± 19). In the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) 59% of measured INR values were between 2.0 and 3.0 . Patients with renal dysfunction, heart failure, frailty, prior valve surgery, and higher bleeding risk had significantly lower time in therapeutic range (TTR: 0–53%) . Of note, many of these adverse characteristics are highly prevalent among TAVR patients, which may explain the lower TTR relative to AF patients. A previous VA study conducted in 100 VA clinics found a mean TTR of 58% among patients with AF . The following should be considered when comparing our data with historical AF cohorts: 1) there is an abundance of long-term efficacy data on the use of anticoagulation among AF patients that could have resulted in a more aggressive approach in AF patients, 2) the ideal target INR for patients post-TAVR is not known, 3) patients with no INRs measured in 60 days have been excluded from AF studies, which might have biased the results . Finally, our results suggest that NOACs may be better suited to achieve the goal of rapid (within 1–2 days post TAVR) and brief (3-month duration) anticoagulation that is highly reproducible across the spectrum of TAVR patients without the need for frequent monitoring.
Several studies are being conducted to test the optimal antithrombotic strategy after TAVR: 1) Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation ( POPular-TAVI , NCT02247128 ) plans to enroll 1000 patients and randomize them into one of four treatment arms (ASA monotherapy, DAPT, oral anticoagulation, or oral anticoagulation plus clopidogrel). The primary end point of POPular-TAVI is freedom from bleeding complication at 1 year, 2) Global Study Comparing a rivaroxaban-based Antithrombotic Strategy to an antiplatelet-based Strategy After Transcatheter aortic valve replacement to Optimize Clinical Outcomes(GALILEO, NCT02556203 ). GALILEO plans to enroll 1500 patients and randomize them to anticoagulation with rivaroxaban plus ASA versus DAPT. The primary end point of GALILEO is a composite of death or first thromboembolic event. A subgroup of 300 patients will be enrolled in the Comparison of a Rivaroxaban-based Strategy With an Antiplatelet-based Strategy Following Successful TAVR for the Prevention of Leaflet Thickening and Reduced Leaflet Motion as Evaluated by Four-dimensional, Volume-rendered Computed Tomography (4DCT) ( GALILEO-4D ). The primary outcome of this sub-study is the proportion of patients with reduce leaflet motion. Until we have definitive answers from randomized clinical trials we think is reasonable to follow ACC/AHA recommendations .