Highlights from

AHA 2019

American Heart Association’s Scientific Sessions

Philadelphia, USA 16 - 18 November 2019

Full GALILEO Results: Why Did Rivaroxaban Fail After TAVR?

Routine oral anticoagulation rivaroxaban therapy caused worse clinical outcomes compared with antiplatelet therapy in patients after successful transcatheter aortic valve replacement (TAVR), the full results of the prematurely stopped GALILEO trial affirm. The GALILEO-4D CT sub-study, however, 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, New York, USA) pointed out that although current guidelines recommend dual antiplatelet therapy after TAVR, the evidence base for optimal treatment strategy for patients undergoing TAVR remains unclear [3]. Previous observational studies have suggested that oral anticoagulation may lower the risk of subclinical leaflet thrombosis, which in turn associates with cerebrovascular events that may develop after TAVR, but an actual test has been lacking.

GALILEO, an open-label trial conducted in 16 countries, was designed to test rivaroxaban for a primary composite efficacy outcome including the rate 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 a rivaroxaban-based or antiplatelet treatment regimen. In the former group, patients received rivaroxaban 10 mg daily plus aspirin 75-100 mg daily for 3 months before continuing with rivaroxaban alone. In the antiplatelet group, patients received aspirin plus clopidogrel 75 mg daily for 3 months before continuing with aspirin alone.

As seen in a preliminary analysis that brought the study to a halt more than a year ago, 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). Death alone was significantly increased as well (7.7% vs 4.6%; HR 1.69; 95% CI 1.13-2.53).

Serious bleeding was also more frequent in the rivaroxaban arm. Although the primary composite safety outcome of 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), there were significant differences in VARC major, TIMI major/minor, ISTH major, and BARC type 2, 3, or 5 bleeding. Prof. Dangas underscored that the mechanism underlying the increase in death, which was primarily driven by non-cardiovascular events, cannot be explained by bleeding and remains uncertain.

In contrast, a 231-patient, 4-dimensional CT, pre-planned sub-study, called GALILEO-4D, was presented by Prof. Ole De Backer (Copenhagen University Hospital, Denmark) in the same session [4]. GALILEO-4D showed that rivaroxaban significantly ameliorated subclinical leaflet thickening: 12.4% with rivaroxaban-based strategy versus 32.4% with clopidogrel-based strategy (P<0.05). Furthermore, the proportion of patients with ≥ 1 prosthetic leaflet with reduced leaflet motion was 2.1% with rivaroxaban-based strategy versus 10.9% with clopidogrel-based strategy (P=0.014).

In conclusion, although leaflet improvements were observed, rivaroxaban-based strategy worsened clinical outcomes in addition to bleeding, showing that the field will have to look elsewhere in the search for effective antithrombotic regimens following TAVR.

The seemingly contrasting conclusions between the studies point to a host of unresolved questions about GALILEO revolving around patient population, dosing strategy, intervention timing, a confounding relationship of thromboembolic events and death with treatment interruption or discontinuation or physician response to bleeding, the incidence of subclinical paroxysmal A-fib, or the effect of atrial fibrillation. GALILEO also had a very medically complicated, high-risk patient population with a mean age of 80 years.

  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. American Heart Association Annual Scientific Sessions (AHA 2019), 14-18 November, Philadelphia, PA, 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. American Heart Association Annual Scientific Sessions (AHA 2019), 14-18 November, Philadelphia, PA, USA.

Top image: @ iStockPhoto: Noctiluxx

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.