Advice for healthcare professionals:
- preliminary analysis of a phase 3 clinical trial show risks of all-cause death and bleeding post-TAVR were approximately doubled in patients assigned to a rivaroxaban-based anticoagulation strategy compared with those assigned to receive an antiplatelet-based strategy (clopidogrel and aspirin)
- rivaroxaban is not authorised for thromboprophylaxis in patients with prosthetic heart valves, including patients who have undergone TAVR, and should not be used in such patients
- rivaroxaban treatment in patients who undergo TAVR should be stopped and switched to standard of care
- the direct-acting oral anticoagulants apixaban and edoxaban have not been studied in patients with prosthetic heart valves and their use is also not recommended in these patients; the use of dabigatran is contraindicated in patients with prosthetic heart valves requiring anticoagulant treatment
- report any suspected adverse drug reactions to rivaroxaban on a Yellow Card
GALILEO study design and findings
Study 17938 (GALILEO) is a randomised, open label, active-controlled, multicentre, phase 3 trial that aimed to assess clinical outcomes after successful TAVR in patients randomly assigned to receive either a rivaroxaban-based anticoagulation strategy or an antiplatelet-based strategy.
The first group was assigned to receive rivaroxaban 10 mg once a day and acetylsalicylic acid (aspirin) 75–100 mg once a day for 90 days followed by maintenance with rivaroxaban 10 mg once a day. The comparator group was assigned to receive clopidogrel 75 mg and acetylsalicylic acid 75–100 mg once a day for 90 days, followed by acetylsalicylic acid alone.
The primary efficacy endpoint is a composite of all-cause death, stroke, systemic embolism, myocardial infarction, pulmonary embolism, deep vein thrombosis, and symptomatic valve thrombosis. The primary safety endpoint is a composite of life-threatening or disabling (BARC types 5 and 3b/3c) and major (BARC type 3a) bleeding events. Patients with atrial fibrillation at randomisation were excluded.
The trial was stopped in August 2018, on recommendation of the independent Data Safety Monitoring Board (DSMB), following a preliminary analysis of available data. The trial findings suggested an imbalance between the two study groups in all-cause mortality, thromboembolic, and bleeding events (see table).
These results are preliminary and based on incomplete data collection. The final study data will be assessed by regulatory authorities as soon as they are available, including an assessment of any implications for approved indications. We will promptly communicate any relevant updates.
Table: Preliminary findings of Study 17938.
||Rivaroxaban group (n=826)
||Antiplatelet group (n=818)
|Death or first thromboembolic events
|Primary bleeding events
|Data are number of events (% patients)
Xarelto▼ (rivaroxaban) is a direct inhibitor of coagulation factor Xa with the following indications:
Co-administered with acetylsalicylic acid alone or with acetylsalicylic acid plus clopidogrel or ticlopidine, for prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers (2.5 mg)
Co-administered with acetylsalicylic acid, for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events (2.5 mg)
Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery (10 mg)
Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (15 mg and 20 mg)
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults (10 mg, 15 mg, and 20 mg).
Rivaroxaban is not approved for thromboprophylaxis in patients with prosthetic heart valves, including patients who have undergone TAVR, and should not be used in such patients.
Report any suspected adverse drug reactions
Xarelto▼ (rivaroxaban) is a black triangle drug. Please continue to report any suspected adverse drug reactions associated with rivaroxaban to the MHRA through the Yellow Card Scheme.
When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, product brand name, and batch number.
Article citation: Drug Safety Update volume 12, issue 3: October 2018: 1.