Reviewer: Dr. Bengisu Keskin Meriç

Name of the Study: Predictors of mortality after successful TAVR: results from the GALILEO trial

Published Congress: EuroPCR 2022

Background: Patients undergoing transcatheter aortic valve replacement (TAVR) are mostly older and more frail individuals with both cardiovascular and non-cardiovascular comorbidities. Therefore, the risk of thromboembolism and bleeding is higher in this group than in the normal population. The optimal antithrombotic therapy after TAVR is unknown and has been empirically determined.

Objectives: The aim of this study was to evaluate predictors of mortality after successful TAVR in the Galileo study. The primary aim of the GALILEO study was to compare the efficacy of a rivaroxaban-based antithrombotic strategy with an antiplatelet-based antithrombotic strategy for the prevention of death or thromboembolic event in patients without an indication for chronic OAC after successful TAVR.

Methods: The GALILEO study was a multicenter, randomized, open-label, international phase III study. Approximately 1,520 patients aged 18 years and older who successfully completed a TAVR procedure (natural valve or in-valve valve) via iliofemoral or subclavian access with any approved device were enrolled in the study. Atrial fibrillation before or during randomization, any indication of OAC, known bleeding diathesis, ongoing absolute indication for dual antiplatelet therapy at screening, stroke within last 3 months, coronary or vascular intervention or major surgery planned, severe renal failure (predicted glomerular Patients with a filtration rate of 30 mL/min per 1.73 m2), acute kidney injury that did not improve after TAVR, moderate hepatic failure, and any liver disease associated with coagulopathy were excluded from the study. Patients were randomized 1:1 to either a rivaroxaban-based strategy or an antiplatelet-based strategy 1 to 7 days after successful TAVR and before hospital discharge. For those randomized to the rivaroxaban-based strategy (experimental arm), rivaroxaban (10 mg 1x1) was initiated at randomization or within 1 to 3 days of last clopidogrel intake. The primary outcomes of the study were all-cause death, stroke, myocardial infarction (MI), symptomatic valve thrombosis, pulmonary embolism (PE), deep vein thrombosis (DVT) and non-central nervous system (CNS) thromboembolic events. The primary safety outcomes were consists of life-threatening or major bleeding.

Results: The median duration of all-cause death was 248 days, and overall mortality was 9.2% (5.5% cardiovascular). The median time to the first thromboembolic event (8.5%) was 151 days. In order of frequency of thromboembolic events; stroke, MI, symptomatic valve thrombosis, DVT, pulmonary embolism, and systemic embolism. Bleeding events(%18,2)  were observed at a median 66 days after TAVI, BARC types 2 and 1 were the most common bleeding types. However, even after excluding thromboembolic events with death within 7 days, the time to death after a thromboembolic event was shorter than after a BARC 2 or 3 bleeding event (median 36 vs 178 days). According to the Kaplan Meier curve, death after thromboembolism reached 54.4% within the 36-day period. The 178-day mortality rate after a BARC 2 or 3 bleeding was 17% according to the Kaplan Meier curve. All BARC bleeding categories except type 1 were found to be associated with mortality. However, the association between thromboembolic events and death was significantly greater than for bleeding (adjusted HR 8.41; 95% CI 5.10-13.87).

Predictors of mortality in the study;
Age > 85, (HR = 2.04) (p = 0.0004)
Male gender, (HR = 2.25) (p = 0.002)
Hemoglobin < 10g/dl, (HR = 1.77) (p = 0.01)
COPD (p = 0.006)
Peripheral arterial disease, (p = 0.02)
GFR < 45 ml/min, (p = 0.02)
NYHA III or IV, (P = 0.02) were detected.

However, these variables associated with increased risk of death have a rather low discriminatory power.

Conclusion: In the GALILEO study; Clinical features such as age> 85 years, male gender, low hemoglobin were associated with early death after TAVI implantation. Although thromboembolic events were observed less frequently than bleeding events, they were associated with a higher risk of death.

Interpretations: The balance between ischemic risk and hemorrhagic risk is complex after TAVI and requires further studies. Because the GALILEO trial included a very large patient population, results were similar to the daily living patient population.