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.
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.
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
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
10. Known allergy to iodinated contrast material
11. Pregnancy or breast feeding