Atrial Fibrillation, Bleeding, Stroke
Conditions
Keywords
Atrial Fibrillation, Rivaroxaban, Warfarin, Stroke, Anticoagulation, Bleeding
Brief summary
This prospective, randomized, active-controlled, parallel arm study compares the safety and financial benefits of arterial thromboembolism prophylaxis with Warfarin vs. Rivaroxaban (A novel oral anticoagulant) in patients with new onset atrial fibrillation after sternotomy for cardiac operations.
Detailed description
New onset atrial fibrillation (NOAF) is a common occurrence following cardiac surgery, occurring in 20-30% of patients post-operatively. Historically, Vitamin K antagonist therapy with Warfarin has been the treatment of choice for prophylaxis against stroke and systemic arterial thromboembolism in NOAF. Warfarin inhibits the Vitamin K dependent factors involved in both the intrinsic and extrinsic coagulation cascades, thus decreasing systemic clotting. However, Warfarin therapy comes with many challenges including prolonged titration, tedious monitoring requirements and in some cases, increased bleeding risk. The limitations associated with Warfarin may be mitigated by using new oral anticoagulants (NOACs) like Rivaroxaban which have no routine monitoring requirements. Rivaroxaban is a direct inhibitor of Factor Xa, a central reactant in both the intrinsic and extrinsic coagulation cascades. Studies in non-operative patients with atrial fibrillation have shown that Rivaroxaban is non-inferior to Warfarin for stroke prophylaxis with similar risk profiles. This study aims to compare the efficacy, safety and financial cost of these two drugs when used for the management of new onset atrial fibrillation that occurs after cardiac operations.
Interventions
DRUGRivaroxaban
Anticoagulant drug that works via direct inhibition of factor Xa. FDA approved for prophylaxis against stroke in non-valvular atrial fibrillation
DRUGWarfarin
Anticoagulation drug that works via inhibition of vitamin K dependent clotting factors. FDA approved for prophylaxis against stroke in atrial fibrillation
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
Statisticians performing comparative analyses of primary outcomes will be blinded as to the allocation designations of patients. Otherwise there will be no masking in the study.
Intervention model description
Cardiac surgery patients who meet study criteria and develop recurrent or persistent atrial fibrillation post-operatively will be randomized 1:1 to receive Warfarin or Rivaroxaban for prophylaxis against stroke or other systemic arterial embolism
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or Female ≥ 18 years * At least one of the following procedures: coronary artery bypass grafting, aortic valve repair, mitral valve repair, non-mechanical aortic valve replacement, any combination of these procedures * Two or more episodes of New Onset Atrial Fibrillation (each lasting \> 20 minutes) or persistent atrial fibrillation lasting \> 24 hours (Or for \>18 hours over a 24-hour interval) * If female of child-bearing age, use of adequate contraception
Exclusion criteria
* Pre-existing paroxysmal atrial fibrillation before cardiac surgery * Pre-existing indications for therapeutic anticoagulation (Including but not limited to PE, DVT, mechanical valve) * Moderate-to-severe mitral valve stenosis not surgically corrected * Pre-existing allergy to study medications * Recent (\< 1 year) or ongoing pregnancy (Urine pregnancy test will be obtained for women of child bearing age at the time of enrollment into the study) * Stroke within 1 month prior to surgery or postoperatively prior to initiation of study drugs * Postoperative bleeding episode prior to initiation of study drug * Severe dysfunction of another organ system including GFR \< 30 ml/min, baseline INR \> 1.7, ileus or other gastrointestinal pathology hindering ability to absorb oral medications, and known coagulation pathway deficiencies * Postoperative need for non-aspirin anti-platelet therapy that cannot be discontinued when therapeutic anticoagulation is initiated * Patient taking medications with known major interactions with study drugs with no therapeutic alternatives)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Length of Stay | Up to 6 months following the cardiac operation | Length of inpatient stay in days from time of departure from the operating room |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Episode of Major Bleeding (Defined as the Occurrence of Any of Several Events Listed in the Description. No Specific Scale, Questionnaire or Instrument Will be Used) | Up to 30 days after discharge from the initial postoperative hospitalization | Major bleeding defined as re-operation or other therapeutic intervention for bleeding (including but not limited to colonoscopy, upper endoscopy and urologic procedures for hematuria), development of any intracranial bleeding, cessation of study drug for bleeding concerns, reversal of study drug for bleeding concerns and/or new transfusion requirement \> 2 units of blood after drug administration |
| Cerebrovascular Accident (CVA) | Up to 30 days after discharge from the initial postoperative hospitalization | Rates of cerebrovascular accident including stroke and transient ischemic attack (TIA) |
| Other Systemic Embolism | Up to 30 days after discharge from the initial postoperative hospitalization | Rates of non-neurological systemic arterial embolism involving any organ system |
| Deep Venous Thrombosis (DVT) and/or Pulmonary Embolism (PE) | Up to 30 days after discharge from the initial postoperative hospitalization | Occurrence of pathologic venous thrombo-embolism including DVT and PE |
| Minor Bleeding | Up to 30 days after discharge from the initial postoperative hospitalization | Minor bleeding defined as blood transfusions \<= 2 units or drop in hemoglobin greater 3g/dL following administration of study drugs |
| Performance on the EUROQOL (EQ-5D) Quality of Life Instrument | Up to 30 days after discharge from the initial postoperative hospitalization | Participants will be administered the EUROQOL-5D-3L (5 dimensions, 3 levels) questionnaire to derive an estimate of the health state. This is comprised of a 5 questions survey and a single visual analog scale highlighting perceived health levels For the 5 questions survey, each question related to mobility, selfcare, mood, pain and/or functionality is answered on a three point scale with higher number representing worse outcomes. The entire dataset is used to generate a health state based on the unique pattern of answers. These health states are then compared against standardized country-based value sets which provide an assessment of quality of life based on societal preferences. |
| Performance on the EUROQOL (EQ-5D) Quality of Life Instrument - VAS | Up to 30 days after discharge from the initial postoperative hospitalization | Participants will be administered the EUROQOL-5D-3L (5 dimensions, 3 levels) questionnaire to derive an estimate of the health state. This is comprised of a 5 questions survey and a single visual analog scale highlighting perceived health levels For the 5 questions survey, each question related to mobility, selfcare, mood, pain and/or functionality is answered on a three point scale with higher number representing worse outcomes. The entire dataset is used to generate a health state based on the unique pattern of answers. These health states are then compared against standardized country-based value sets which provide an assessment of quality of life based on societal preferences. The visual analog scale is single answer between 0 and 100 representing the patient's perception of their health state. 0 represents the worst health imaginable and 100 represents the best. |
| Average Score on the Perception of Anticoagulant Treatment Questionnaire (PACT-Q2) | Up to 30 days after discharge from the initial postoperative hospitalization | Participants will be administered the PACT-Q2 questionnaire which is comprised of a convenience subscale and a satisfaction subscale. For the convenience subscale, each of 13 questions is answered on a 1-5 rating scale with higher numbers representing worse outcomes. A sub-scale score is generated by inverting the score from each element and calculating the sum. Range on the inverted scale is 13 - 65. Higher scores represent better outcomes. For the satisfaction subscale, each of 7 questions is answered on a 1-5 rating scale with higher numbers representing better outcomes. The total score on this subscale is generated by adding up scores from all elements. Range on this subscale is 7-35. Higher scores represent better outcomes. A composite score is generated by adding up scores from both subscales and recalibrating on a 0-100 scale by adding the scores together and applying the formula: COMPOSITE SCORE=100×(Sum-20)/80. Higher scores represent more favorable outcomes. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAsishana A Osho, MD, MPH
Massachusetts General Hospital
PRINCIPAL_INVESTIGATORThoralf M Sundt, MD
Massachusetts General Hospital
Participant flow
Recruitment details
The study was conducted at a large quaternary referral hospital in the United States, and patients were enrolled from April 2019 to June 2023. Patients were screened for enrollment after developing persistent or recurrent atrial fibrillation during their index hospitalization after undergoing an eligible cardiac surgery operation.
Pre-assignment details
No events occurred between enrollment and assignment to a study arm.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 7.6 |
| Procedure Aortic Arch | 0 Participants |
| Procedure Aortic Root | 2 Participants |
| Procedure Aortic Valve Surgery - Repair | 0 Participants |
| Procedure Aortic Valve Surgery - Replacement - Biological | 13 Participants |
| Procedure Ascending Aorta - Replacement | 0 Participants |
| Procedure Combination of Procedures | 17 Participants |
| Procedure Coronary Artery Bypass | 21 Participants |
| Procedure Mitral Valve Surgery - Repair | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 95 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 3 / 50 | 1 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
None listed