Bleeding Post Cardiac Surgery, Indication for Anticoagulation
Conditions
Keywords
Direct Oral Anticoagulant, Vitamin K Antagonist, Bleeding
Brief summary
The DANCE Trial is a multi-centre, randomized controlled trial comparing the safety of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) in the early period (30 days) after cardiac surgery in patients with atrial fibrillation requiring oral anticoagulation.
Detailed description
Approximately 36,000 Canadian adults undergo cardiac surgery annually. Of these patients, about 10% have a prior history of atrial fibrillation (AF). In the early post-operative period after cardiac surgery, 30-60% of patients develop AF and, by the time of discharge, 32% of patients who underwent cardiac surgery have an indication for oral anticoagulation (OAC). AF is associated with a significantly higher risk of stroke, even when transient, and OAC is the standard for thromboembolic prevention in these patients. In the post-operative period, the balance of benefits and risks of OAC may differ and the safest and most effective OAC in that patient population is uncertain. Vitamin K antagonists (VKAs), such as warfarin or coumadin, are the most used anticoagulants after cardiac surgery. In the Left Atrial Appendage Occlusion Study (LAAOS) III that recruited 4811 patients from 105 centres in 27 countries, 77% of patients with AF on OAC were discharged on a VKA after cardiac surgery. Among patients taking a DOAC preoperatively, 55% were switched to a VKA after surgery. Over the first post-operative year, most of those patients were gradually transitioned back to a DOAC. Although effective, the use of VKAs is limited by a narrow therapeutic index requiring frequent international normalized ratio (INR) measurements to ensure appropriate levels of anticoagulation. This key limitation leads to non-compliance and discontinuation. In addition, in the first 3 months after cardiac surgery, time in the therapeutic range is low, even with close monitoring by experienced prescribers. In the last decade, DOACs - inhibitors of factor Xa or thrombin- have become broadly used in patients with AF. Treatment with a DOAC in patients with AF has been demonstrated to yield a lower risk of stroke or systemic embolism and a similar risk of major bleeding when compared to VKAs during long-term follow-up. Moreover, DOACs are more convenient for both patients and clinicians. They have a rapid onset of effect, fixed dosage that obviates the need for regular monitoring, and few interactions with food and other medications. In the postoperative setting, DOACs may also lead to shorter length of stay and reduced costs. The purpose of this study is to establish whether DOACs are as safe as VKAs in the first few weeks after heart surgery. The results of this study will impact the treatment of hundreds of thousands of patients in the world every year. A subset of 910 DANCE participants with a recent bioprosthetic aortic and/or mitral valve replacement will be enrolled in the SUNDANCE substudy (Subclinical valve thrombosis in patients with surgical bioprosthetic valve replacement: An imaging substudy of the DANCE trial). SUNDANCE will examine the effects of DOACs versus VKAs on subclinical valve thrombosis and bioprosthetic valve function by conducting computed tomography (CT) scans and echocardiograms at 60 to 90 days after randomization.
Interventions
DRUGDOAC
Patients will receive a DOAC at doses recommended for the indication, adjusted for their renal function is required. The choice of DOAC will be at the discretion of the treating physician.
DRUGVKA
Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range.
Sponsors
Hamilton Health Sciences Corporation
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years at the time of enrolment, 2. Open heart surgery in the last 10 days, 3. Atrial fibrillation requiring anticoagulation (including pre-existing or post-operative atrial fibrillation), 4. Informed consent from either the patient or a substitute decision-maker.
Exclusion criteria
1. Mechanical valve replacement, 2. Antiphospholipid syndrome (triple positive), 3. Severe renal failure (Cockcroft-Gault equation; creatinine clearance \<15 ml/min), 4. Known significant liver disease (Child-Pugh classification B and C), 5. Left ventricular thrombus, 6. Ongoing bleeding, hemorrhagic disorders, or bleeding diathesis, 7. Known contraindication for any DOAC or VKA, 8. Women who are pregnant, breastfeeding, or of childbearing potential, 9. Surgery including left ventricular assist device implantation or cardiac transplantation, 10. Previously enrolled in this trial, 11. Follow-up not possible, 12. History of moderate or severe mitral valvular lesion (stenosis or regurgitation) that is not corrected during index cardiac surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Bleeding | 30-Days post-randomization | Major bleeding at 30 days, defined as bleeding that results in death and/or symptomatic bleeding in a critical area or organ, bleeding into a surgical site requiring reoperation, bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay) and/or bleeding that causes a drop in the hemoglobin level of 20g/L or more or that which requires the transfusion of ≥2 units of packed red blood cells or whole blood (as defined by the International Society of Thrombosis and Hemostasis) |
Secondary
| Measure | Time frame |
|---|---|
| All-Cause Mortality | 6 Months post-randomization |
| Length of post-operative hospital stay | 30-Days and 90-Days post-randomization |
| Composite of stroke and non-central nervous system systemic arterial embolism at 30 and 90 days. | 30-Days and 90-Days post-randomization |
| Major Bleeding | 90-Days post-randomization |
| Pleural or pericardial effusion requiring drainage | 30-Days and 90-Days post-randomization |
| Systemic arterial embolism | 30-Days and 90-Days post-randomization |
| Ischemic stroke | 30-Days and 90-Days post-randomization |
| Deep vein thrombosis | 30-Days and 90-Days post-randomization |
| Pulmonary Embolism | 30-Days and 90-Days post-randomization |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subclinical Valve Thrombosis on CT scan | 60 to 90-Days post-randomization | Substudy outcome |
| Mean Aortic Valve g=Gradient on echocardiogram | 60 to 90-Days post-randomization | Substudy outcome |
| Aortic Valve Reintervention | 60 to 90-Days post-randomization | Substudy outcome |
| Association between subclinical valve thrombosis and clinically significant aortic valve thrombosis, stroke or systemic embolism | 90 days | — |
| Minor Bleeding | 30-Days and 90-Days post-randomization | Tertiary outcome |
| All bleeding (major plus minor) | 30-Days and 90-Days post-randomization | Tertiary outcome |
| Myocardial Infarction | 30-Days and 90-Days post-randomization | — |
| Valve Thrombosis | 30-Days and 90-Days post-randomization | Tertiary outcome |
| Hemorrhagic stroke | 30-Days and 90-Days post-randomization | Tertiary outcome |
| All Stroke | 30-Days and 90-Days post-randomization | Tertiary outcome |
| All Arterial Thrombosis/thromboembolism | 30-Days and 90-Days post-randomization | Tertiary outcome: ischemic stroke, systemic arterial embolism, myocardial infarction, valve thrombosis |
| Quality of Life - EQ-5D-5L | 30-Days and 90-Days post-randomization | Tertiary outcome: Measured by The EQ-5D-5L Questionnaire |
| Patient Satisfaction with Anticoagulant treatment | 30-Days and 90-Days post-randomization | Tertiary outcome: Assessed by the Perception of Anticoagulant Treatment Questionnaire |
Countries
Australia, Canada, Germany
Contacts
Primary ContactEmilie Belley-Cote, MD, MSc
Backup ContactRichard Whitlock, MD, PhD
Outcome results
None listed