Full GALILEO results: Why did rivaroxaban fail after TAVR?

The full results of the prematurely terminated GALILEO trial confirm that oral anticoagulation with rivaroxaban was associated with worse clinical outcomes compared with antiplatelet therapy in patients after successful transcatheter aortic valve replacement (TAVR). However, the GALILEO-4D CT sub-study showed that rivaroxaban prevents some leaflet thickening and leaflet motion, indicative of a specific benefit. Both studies were simultaneously published in the New England Journal of Medicine [1,2].

Prof. George Dangas (Icahn School of Medicine at Mount Sinai, USA) pointed out that although current guidelines recommend dual antiplatelet therapy after TAVR, the evidence base for the optimal treatment strategy for patients who have had TAVR is weak [3]. Earlier observational studies provided some evidence that oral anticoagulation could lower the incidence of sub-clinical leaflet thrombosis, which in turn may prevent post-TAVR cerebrovascular lesions, but high-level evidence has been lacking.

GALILEO was an open-label trial designed to test rivaroxaban for a primary composite efficacy outcome of death or thromboembolic events in patients within a week of successful TAVR. Investigators randomised 1,644 patients (mean age 80.6 years; 49.5% female) without an established indication for oral anticoagulation to either rivaroxaban-based treatment (10 mg daily plus aspirin 75-100 mg daily for 3 months, then maintenance with rivaroxaban alone) or antiplatelet treatment arm (aspirin plus clopidogrel 75 mg daily for 3 months, then maintenance with aspirin alone).

The rate of death or thromboembolic events was higher with rivaroxaban-based therapy than with antiplatelet therapy (12.7% vs 9.5%; HR 1.35; 95% CI 1.01-1.81). The individual endpoint of death was significantly increased in the rivaroxaban treatment arm as well (7.7% vs 4.6%; HR 1.69; 95% CI 1.13-2.53). Consequently, the trial was halted prematurely.

Although serious bleeding was somewhat more frequent in the rivaroxaban arm of the trial, Prof. Dangas presented the data that underlying causes of the observed mortality could not be explained by bleeding and remain uncertain and perhaps related to non-cardiovascular causes. VARC-2 major, disabling, or life-threatening bleeding was only borderline significantly increased (5.6% vs 3.8%; HR 1.50; 95% CI 0.95-2.37), while there were no significant differences in VARC-2 major, TIMI major/minor, ISTH major, and BARC type 2, 3, or 5 bleeding events.

In contrast, presenting a pre-planned sub-study of the 4-dimensional CT data derived from 231 patients in GALILEO, dubbed GALILEO-4D, Prof. Ole De Backer (Copenhagen University Hospital, Denmark) showed data that rivaroxaban significantly reduced subclinical leaflet thickening [4]. Leaflet thickening was noted in 12.4% patients from the rivaroxaban-based strategy arm versus 32.4% of the patients treated with a clopidogrel-based strategy (P<0.05). Furthermore, the percentage of patients with ≥1 prosthetic leaflet with reduced leaflet motion was reduced by rivaroxaban: 2.1% with rivaroxaban-based strategy versus 10.9% with clopidogrel-based strategy (P=0.014).

In conclusion, although leaflet improvements were observed, using a rivaroxaban-based antithrombotic strategy post-TAVR increased mortality in addition to moderately increasing bleeding risk. Thus, novel regimens for antithrombotic management following TAVR remain an area of open research.

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   1. Dangas GD, et al. A Controlled Trial of Rivaroxaban After Transcatheter Aortic-Valve Replacement. N Engl J Med 2019; Nov 16 [Epub ahead of print].
   2. De Backer O. Reduced Leaflet Motion After Transcatheter Aortic-Valve Replacement. N Engl J Med 2019; Nov 16 [Epub ahead of print].
   3. Dangas GD, et al. Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy versus an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes (GALILEO) Trial: Primary Results. Session LBS03, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.
   4. De Backer O, et al. 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). Session LBS03, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.

 



Posted on 26 February 202025 March 2024