Global Study Comparing a Rivaroxaban-based Antithrombotic Strategy to an Antiplatelet-based Strategy After TAVR to Optimize Clinical Outcomes - GALILEO

Jan 09, 2020
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Presenter/Author:
George D. Dangas, MD, PhD, MACC
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Bayer and Janssen Pharmaceuticals
Date Presented:
11/16/2019
Date Published:
01/09/2020
Date Updated:
01/09/2020
Original Posted Date:
11/16/2019
References

Contribution To Literature:

The GALILEO trial showed that after TAVR, a rivaroxaban-based strategy vs. a clopidogrel-based strategy was associated with excess ischemic and bleeding events. 

Description:

The goal of the trial was to evaluate a rivaroxaban-based strategy compared with a clopidogrel-based strategy among patients who underwent transcatheter aortic valve replacement (TAVR).


Study Design

  • Randomized
  • Parallel
  • Open-label

Patients were randomized 1-7 days after TAVR to rivaroxaban 10 mg daily/aspirin 75-100 mg daily (n = 826) versus clopidogrel 75 mg daily/aspirin 75-100 mg daily (n = 818). At 90 days, rivaroxaban alone was continued in the experimental group, while aspirin alone was continued in the control group.

  • Total number of enrollees: 1,644
  • Duration of follow-up: 18 months
  • Mean patient age: 80 years
  • Percentage female: 48%
  • Percentage with diabetes: 29%

Inclusion criteria:

  • Patients ≥18 years of age who underwent successful TAVR
  • Successful TAVR defined as correct position of the valve, no major periprocedural complication, mean gradient <20 mm Hg, peak velocity <3 m/sec, and < moderate paravalvular aortic insufficiency

Exclusion criteria:

  • Atrial fibrillation or other indication for anticoagulation
  • Absolute indication for dual antiplatelet therapy
  • Contraindication to aspirin, clopidogrel, rivaroxaban
  • Bleeding diathesis
  • Routine use of NSAIDs
  • Planned coronary or vascular intervention, or major surgery
  • Stroke within 3 months
  • Significant renal or hepatic insufficiency
  • Active infective endocarditis
  • Active malignancy

Other salient features/characteristics:

  • Sapien 3 valve in 47%
  • Evolut R in 25%

Principal Findings:

The trial was terminated early due to safety concerns. At the time of termination, only 42% of patients had reached the primary outcome.

The primary efficacy outcome of death, myocardial infarction, stroke, systemic thromboembolism, symptomatic valve thrombosis, or deep vein thrombosis/pulmonary embolism occurred in 12.7% of the rivaroxaban group compared with 9.5% of the clopidogrel group (p = 0.04).

The primary safety outcome of Vascular Academic Research Consortium (VARC)-2 major, disabling, or life-threatening bleeding occurred in 5.6% of the rivaroxaban group compared with 3.8% of the clopidogrel group (p = 0.08).

Secondary outcomes:

  • All-cause mortality: 7.7% with rivaroxaban vs. 4.6% with clopidogrel (p = 0.009)
  • Noncardiovascular mortality: 3.5% with rivaroxaban vs. 1.3% with clopidogrel (p < 0.05)
  • VARC-2 major bleeding: 3.6% with rivaroxaban vs. 1.8% with clopidogrel (p < 0.05)

Leaflet thrombosis substudy (GALILEO-4D):

  • Proportion of patients with ≥1 prosthetic leaflet with reduced leaflet motion: 2.1% with rivaroxaban-based strategy vs. 10.9% with clopidogrel-based strategy (p = 0.014)
  • Proportion of patients with ≥1 thickened leaflet: 12.4% with rivaroxaban-based strategy vs. 32.4% with clopidogrel-based strategy (p < 0.05)

Interpretation:

Among patients who underwent TAVR and who did not have an indication for anticoagulation, a rivaroxaban-based strategy was not effective at preventing major adverse cardiovascular events compared with a clopidogrel-based strategy. In fact, the trial was terminated early due to safety concerns. The rivaroxaban-based strategy was associated with an increase in major adverse cardiovascular events, an increase in all-cause mortality (due to excess noncardiovascular mortality), and an increase in major bleeding events.

However, the leaflet thrombosis substudy revealed a lower incidence of leaflet thrombosis with rivaroxaban. The mechanism for these unexpected findings is unknown, especially in light of the leaflet thrombosis substudy. It is unknown if a higher or lower dose of rivaroxaban would have resulted in a more favorable risk to benefit profile.

References:

Dangas GD, Tijssen JG, Wöhrle J, et al., on behalf of the GALILEO Investigators. A Controlled Trial of Rivaroxaban After Transcatheter Aortic-Valve Replacement. N Engl J Med 2020;382:120-9.

De Backer O, Dangas GD, Jilaihawi H, et al., et al., on behalf of the GALILEO-4D Investigators. Reduced Leaflet Motion After Transcatheter Aortic-Valve Replacement. N Engl J Med 2020;382:130-9.

Editorial: Nishimura RA, Holmes DR Jr. Treatment After TAVR — Discordance and Clinical Implications. N Engl J Med 2020;382:193-4.

Presented by Dr. George Dangas at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019 (GALILEO).

Presented by Dr. Ole De Backer at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16, 2019 (GALILEO-4D).

Keywords: AHA19, AHA Annual Scientific Sessions, Anticoagulants, Aortic Valve Insufficiency, Aspirin, Geriatrics, Heart Failure, Heart Valve Diseases, Hemorrhage, Myocardial Infarction, Myocardial Ischemia, Platelet Aggregation Inhibitors, Pulmonary Embolism, Stroke, Thromboembolism, Thrombosis, Transcatheter Aortic Valve Replacement, Venous Thrombosis


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