Atherosclerosis
Conditions
Keywords
atherosclerosis, coronary artery disease, cardiac CT, computed tomographic angiography
Brief summary
Current oral anti-coagulation for atrial fibrillation is most commonly performed with warfarin. Warfarin is a vitamin K antagonist that has been shown in non-randomized trials to increase vascular calcification. Increased vascular calcification has been tied to increased cardiovascular events (CVE). This study will randomize patients currently taking warfarin to either continue on warfarin or be switched to rivaroxaban. Rivaroxaban is an oral anti-coagulant that works by inhibiting Factor Xa, and has no interaction with vitamin K. This study is a randomized, open label study that will randomize 120 patients and have them undergo blood tests and a calcium scan at baseline, and again after 12 months. Patients will be seen quarterly for examinations, safety checks and supply of rivaroxaban, as well as follow up INR testing for warfarin.
Detailed description
Rivaroxaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with warfarin. The rate of myocardial infarction was 9% lower in the rivaroxaban group than in the warfarin group in the Rocket AF study and similarly the myocardial infarction rate was 12% lower in the apixaban group in Aristotle, but the difference was not significant in either trial. The potential of long term benefit by avoiding VKA therapy may be much greater for a CV event reduction. The study proposed will evaluate markers of CAC progression and atherosclerosis development, which have long term outcome data supporting that slowing these processes will be associated with lower CV events.
Interventions
DRUGrivaroxaban
DRUGWarfarin
Sponsors
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
randomized controlled trial, with blinded randomization to one of two groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Eligible patients with atrial fibrillation at enrollment or two or more episodes of atrial fibrillation or flutter, as documented by electrocardiography, at least 2 weeks apart in the 12 months before enrollment 2. Age 18-84 3. On Warfarin for 6 months prior to enrollment at a stable dose. 4. Willingness to participate in the study and ability to sign informed consent 5. Minimum CAC score of 10 Key
Exclusion criteria
1. Atrial fibrillation due to a reversible cause, moderate or severe mitral stenosis, or conditions other than atrial fibrillation that require anticoagulation (e.g., a prosthetic heart valve) 2. Prior apixaban, dabigatran, rivaroxaban use. 3. A need for aspirin at a dose of \>165 mg a day or for both aspirin and clopidogrel, 4. Renal insufficiency (serum creatinine level of 12.5 mg per deciliter or calculated creatinine clearance of \<50 ml per minute). 5. Serious bleeding event in the previous 6 months or a high risk of bleeding (eg, active peptic ulcer disease, a platelet count of \<100,000/mm3 or hemoglobin level of \<10 g/dL, stroke within the previous 10 days, documented hemorrhagic tendencies, or blood dyscrasias) 6. Weight in excess of 325 pounds 7. Resting hypotension (systolic blood pressure of \<90mmHg) or resting hypertension (systolic blood pressure of \>170mmHg or diastolic blood pressure of \>110 mmHg). 8. History of active malignancy requiring concurrent chemotherapy. 9. Any unstable medical, psychiatric, or substance abuse disorder that in the opinion of the principal investigator is likely to affect the subject's ability to complete the study. 10. Known allergy to iodinated contrast material 11. Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Coronary Artery Calcium (Serial Calcium Scans) | 1 year | serial calcium scans |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA) | 1 year | measures of total atherosclerosis plaque on serial CCTA |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivaroxaban rivaroxaban will be given to this cohort, once daily orally (15 or 20 mg, depending on GFR)
rivaroxaban | 55 |
| Warfarin warfarin orally once a day, titrated to INR of 2-3
Warfarin | 55 |
| Total | 110 |
Baseline characteristics
| Characteristic | Warfarin | Total | Rivaroxaban |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 27 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 83 Participants | 42 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 11 | 61 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 22 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 85 Participants | 43 Participants |
| Region of Enrollment United States | 55 Participants | 110 Participants | 55 Participants |
| Sex: Female, Male Female | 17 Participants | 33 Participants | 16 Participants |
| Sex: Female, Male Male | 38 Participants | 77 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 51 |
| other Total, other adverse events | 1 / 46 | 2 / 51 |
| serious Total, serious adverse events | 0 / 46 | 0 / 51 |
Outcome results
Primary
Coronary Artery Calcium (Serial Calcium Scans)
serial calcium scans
Time frame: 1 year
Population: patients completed second scan with interpretable data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rivaroxaban | Coronary Artery Calcium (Serial Calcium Scans) | 26.3 mm cubed |
| Warfarin | Coronary Artery Calcium (Serial Calcium Scans) | 40.5 mm cubed |
Secondary
Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA)
measures of total atherosclerosis plaque on serial CCTA
Time frame: 1 year
Population: volume of plaque in patients completing study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rivaroxaban | Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA) | 20.1 mm cubed |
| Warfarin | Atherosclerotic Plaque (Measures of Total Atherosclerosis Plaque on Serial CCTA) | 30.1 mm cubed |