Rivaroxaban Use Following TAVR Increases Risk of Death, Bleeding

George Dangas, MD, PhD

A new study has found treatment with rivaroxaban following transcatheter aortic valve replacement(TAVR) was associated with an elevated risk of death and bleeding compared to anti-platelet based antithrombotic strategy.

Presented at American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, results of the Global Study Comparing Rivaroxaban Antithrombotic Strategy to an Antiplatelet Strategy Based Strategy After TAVR (GALILEO) trial revealed 10 mg rivaroxaban was associated with increased risk in patient with no indication for oral anticoagulation.

“In patients without an indication for oral anticoagulation after TAVR, a 10 mg daily rivaroxaban antithrombotic strategy in the GALILEO trial was associated with higher risk of death or thromboembolic events and bleeding,” said George Dangas, MD, PhD, study presenter and professor of medicine at the Mount Sinai School of Medicine.

GALILEO was designed as an open-label, multicenter, event-driven, randomized, controlled trial designed to compare antithrombotic strategy versus antiplatelet-based strategy following a successful TAVR procedure. For inclusion in GALILEO, patients needed to be at least 18 years of age, have completed a successful transferal or trans-subclavian TAVR, and TAVR must have been performed with an approved device.

Patients were excluded if they had atrial fibrillation with an indication for direct oral anticoagulants, the need for chronic oral anticoagulation, contraindication to aspirin, clopidogrel, or rivaroxaban, routinely used NSAIDs, or severe renal impairment among other criteria.

In all, 1644 patients were included in the study and they were randomized in a 1:1 ratio to either the rivaroxaban or acetylsalicylic acid (ASA). For the purpose of the study, patients in the rivaroxaban group received 10 mg rivaroxaban and 75 to 100 mg of ASA for the first 90 days and then ASA therapy was discontinued—whereas, patients in the ASA arm received 75 to 100 mg of ASA and 75 mg of clopidogrel once daily for the first 90 days then clopidogrel was discontinued.

The primary efficacy measure of the study was death, stroke, myocardial infarction, systemic thromboembolism, symptomatic valve thrombosis, or deep venous thrombosis or pulmonary embolism. The primary safety endpoint of the study was Valve Academic Research Consortium(VARC)-2 major, disabling, or life-threatening bleeding.

In an intention-to-treat analysis, investigators found the patients in the rivaroxaban arm were at a 1.35-fold increased risk in terms of the study’s primary efficacy endpoint (HR 1.35, 95% CI: 1.01-1.81, P=0.04). Additionally, investigators noted 105 events occurred in patients receiving rivaroxaban over the course of 720 days compared to 78 events in the antiplatelet arm (9.8 versus 7.2 per 100 person-years, respectively).

In regard to the primary safety endpoint, an intention-to-treated analysis revealed a hazard ratio of 1.50 for the rivaroxaban arm compared to the antiplatelet arm (95% CI: 0.95-2.37, P=0.08). A total of 46 (4.3 per 100 person-years) events occurred in the rivaroxaban arm compared to 31 (2.8 per 100 person-years) events in the antiplatelet arm over 720 days.

When examining only all-cause mortality, investigators noted rivaroxaban patients were at a 1.69-fold increased risk, with 64 events taking place during the study period compared to 38 events in the antiplatelet group (95% CI: 1.13-2.53, P=0.009).

This study, “Global Comparison of a Rivaroxaban-Based Antithrombotic Strategy versus an Antiplatelet-Based Strategy After Transcathether Aortic Valve Replacement to Optimize Clinical Outcomes (GALILEO) Trial: Primary Results,” was presented by George Dangas, MD, PhD, at AHA 2019.