NOAC-based strategy after TAVR may cause harm with respect to clinical outcomes, but in contrast reduces leaflet thrombosis
Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After TAVR: Main Results of The GALILEO Trial
Presented during the AHA Scientific Sessions 2019 by George Dangas (New York, NY).
Randomized Clinical Trial Comparing a Rivaroxaban-Based Strategy With an Antiplatelet-Based Strategy for the Prevention of Subclinical Leaflet Thrombosis in Transcatheter Aortic Valves (GALILEO-4D)
Presented during the AHA Scientific Sessions 2019 by Ole De Backer (Copenhagen, Denmark).
Introduction and methods
Risk of thromboembolic events is high in patients undergoing transcatheter aortic valve replacement (TAVR). Thus far, it is unknown what the optimal antithrombotic therapy is after TAVR. Therefore, the GALILEO trial (Global Study Comparing a rivAroxaban-based Antithrombotic Strategy to an antipLatelet-based Strategy After TAVR) examined whether a rivaroxaban-based strategy was superior to an antiplatelet-based strategy in reducing death and thromboembolic events in patients after successful TAVR without an ongoing indication for oral anticoagulation (such as atrial fibrillation).
The GALILEO trial was a global, multicenter, open-label, randomized, event-driven, active-controlled phase 3 trial. 1644 Patients were randomized to rivaroxaban 10 mg plus aspirin for 90 days followed by rivaroxaban 10 mg alone or clopidogrel 75 mg plus aspirin for 90 days followed by aspirin alone within 1 week after successful TAVR.
Primary efficacy endpoint was a composite of all-cause death or thromboembolic events (including any stroke, MI, symptomatic valve thrombosis, non-central nervous system systemic embolism, deep venous thrombosis or pulmonary embolism). The primary safety endpoint was the composite of major, disabling or life-threatening bleeding events according to VARC-2 criteria.
The trial was stopped early due to reasons of adverse patient safety. Median follow-up was 17 months.
There have been reports of subclinical leaflet thrombosis in bioprosthetic aortic valves. Subclinical leaflet thrombosis can be described as hypo-attenuating leaflet thickening (HALT) with or without reduced leaflet thickening (RLM), measured by cardiac four-dimensional computed tomography (4DCT). It has not been studied in RCTs whether DOAC therapy results in reduction of subclinical leaflet thrombosis.
Therefore, the GALILEO-4D trial was conducted, as a substudy of the main GALILEO trial. 231 Patients underwent transthoracic echocardiography and cardiac 4DCT at 90 days after randomization to either the rivaroxaban-based strategy or the antiplatelet regime. The degree of RLM was defined as grade 0: normal/unrestricted, grade 1: minimally restricted (<25%), grade 2: mildly restricted (25-50%), grade 3: moderately restricted (50-75%), grade 4: largely immobile (>75%).
The primary endpoint was the proportion of patients with at least one prosthetic valve leaflet with RLM ≥ grade 3.
Main trial results
- Event rate of the primary efficacy endpoint was higher in the rivaroxaban strategy group compared to the antiplatelet regime group (9.8 events per 100 PYs vs. 7.2 events, HR: 1.35, 95%CI: 1.01.-1.81, P=0.04).
- Event rate of the primary safety endpoint was higher in the rivaroxaban strategy group compared to the antiplatelet regime group ( 4.3 events per 100 PYs vs 2.8, HR: 1.50, 95%CI: 0.95-2.37, P=0.08).
- Net clinical benefit, the composite of primary efficacy and safety endpoints, was increased in the rivaroxaban group compared to the antiplatelet group (HR: 1.39, 95%CI: 1.08-1.80).
- All-cause mortality was higher in the rivaroxaban regime group compared to the antiplatelet-based therapy group (5.8 vs. 3.4 per 100 PYs, HR: 1.69, 95%C: 1.13-2.53, P=0.009), driven by a significant difference in non-CV death.
Subclinical leaflet thrombosis results
- The percentage of patients with RLM ≥grade 3 was lower in the rivaroxaban group compared to the antiplatelet group (2.1 vs. 10.9%, risk ratio: 0.19, 95%CI:0.04-0.83, P=0.014).
- The percentage of patients with leaflet thickening was also lower in the rivaroxaban group vs. the antiplatelet group (12.4% vs. 32.4%, risk ratio:0.38, 95%CI: 0.21-0.70).
- There were very few clinical events and therefore assessment of association between parameters RLM and HALT with clinical outcomes was not possible.
In patients undergoing TAVR and without any indication for following oral anticoagulation, a regime of rivaroxaban-based therapy was associated with an increased risk of all-cause death or thromboembolic events and bleeding events when compared to an antiplatelet-based strategy. In contrast, in a substudy with cardiac 4DCT, the proportion of patients with parameters of subclinical leaflet thrombosis were reduced in those treated with rivaroxaban-based strategy compared to an antiplatelet-based regime.
- Our reporting is based on the information provided during AHA Scientific Sessions 2019 -