Apixaban Versus Warfarin in the Evaluation of Progression of Atherosclerotic Calcification and Vulnerable Plaque
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation; Calcinosis
Study type: Interventional
Phase: Phase 4

Summary: 
      Vitamin K-antagonists (VKA) such as warfarin are the most widely used blood thinners for
      irregular heart beats like atrial fibrillation. Several lines of evidence indicate, however,
      that these agents also cause calcification of vessels (hardening of the vessels). Vascular
      calcification is one of the recently revealed side-effects of warfarin therapy. We will be
      randomizing 66 patients to either take warfarin or a new blood thinner that works without
      affecting vitamin k (apixaban). Patients will undergo blood testing and a CT angiogram
      (non-invasive angiogram) at the beginning of the study, and then be followed for one year
      with quarterly visits including blood tests and given either warfarin or vitamin K. After one
      year, they will undergo another CT angiogram and examination and blood tests and the effect
      of apixaban and warfarin are tested to look at plaque and changes over time. Patients will be
      consented in a private room and the risks and benefits will be explained. The risks include
      the CT angiogram and the possibility of either remaining on warfarin therapy for another year
      (standard of care) or taking a medicine that doesn't require monitoring (apixaban) for one
      year. The CT angiograms will require some contrast and some radiation dose, which will be
      minimized as much as possible. A cardiologist will be present during each CT angiogram to
      minimize risk and ensure patient safety.
    

Detailed description: 
      The progression of atherosclerotic plaques characterized by various anatomic plaque
      composition changes has been acknowledged to be associated with increased plaque rupture,
      myocardial infarction and death. Coronary computed tomography angiography (CCTA) has emerged
      as a novel non-invasive modality with high diagnostic performance for detection and
      assessment of atheroma compared to invasive coronary angiography (ICA) and intravascular
      ultrasound (IVUS). Beyond stenosis severity, CCTA also permits anatomic quantification of
      numerous atheroscleroticStudy design This is a prospective, single-centered, randomized,
      open-label trial with blinded adjudication of results (plaque composition) designed to
      compare apixaban (2.5 mg or 5 mg BID per the current guideline) with warfarin (target
      international normalized ratio, 2.0 to 3.0) for 52 weeks on calcified plaque, coronary plaque
      composition and volume in patients with non-valvular AF.

      Study population The targeted population included patients aged 18-84 years with non-valvular
      AF or flutter at enrollment or two more episodes of AF (as documented by electrocardiography)
      at least 2 weeks apart in the 12 months before enrollment. The inclusion and exclusion
      criteria were shown in detail in a recent paper. Subjects were enrolled from May 2014 to
      December 2015 and randomized into warfarin group (VKA_group) or apixaban group (Api_group).
      Of the 66 originally enrolled patients, 56 had complete data at final follow-up, including
      interpretable CCTA scans at baseline and follow-up. All subjects were followed up for a total
      52 weeks.

      Coronary CTA scan protocol All CT scans were performed with a 64-slice CT scanner (Lightspeed
      VCT; General Electric Healthcare Technologies, Milwaukee, WI, USA), or 256-slice CT scanner
      (Revolution CT; General Electric Healthcare Technologies, Milwaukee, WI, USA). Before CCTA, a
      prospective non-enhanced coronary calcium (CAC) scan was performed. For quantitative
      assessment of CAC, the Agatston score was calculated, using a 3 mm CT slice thickness and a
      detection threshold of ≥130 HU involving ≥1 mm2 area/lesion (3 pixels). CCTA was performed
      using a collimation of 64 × 0.625 mm or 256 × 0.625 mm and a rotation time of 0.4 s or 0.28
      s. The tube current was 400-770 mA (depending on body weight), at 100-120 kV. Contrast
      material at a flow rate of 5.0 mL/s was administered in the antecubital vein, with volumes
      depending on the total scan time (60-80 mL). In the absence of contraindications, patients
      with a heart rate ≥60 bpm were administered 50-100 mg metoprolol oral and up to 40 mg
      metoprolol intravenous if needed. Interpretation was performed by expert reading by an
      experienced cardiologist (M.J.B) blinded to all clinical data.

      plaque phenotypes, plaque burden and ability to differentiate between various plaque types.
      Also, recent technology providing low radiation dose for CCTA with approximately < 1-3mSv
      allows us to investigate the effects of different therapies using serial CCTA.

      Warfarin, a vitamin K antagonist (VKA) and one of the most commonly used oral
      anti-coagulants, has been showed to increase vascular calcification leading to increased
      cardiovascular (CV) events. However, apixaban, a direct Factor Xa inhibitor, has no
      interaction with vitamin K and its effect on the progression of atherosclerotic plaques is
      still unknown. The potential benefit of avoiding VKA therapy and the favorable effects of
      factor Xa inhibitors may contribute to a reduction in CV events. We aimed to compare apixaban
      with warfarin on progression of coronary plaque composition and volume in non-valvular AF
      patients using CCTA.
    

Intervention name(s): apixaban; warfarin
Intervention type(s): Drug; Drug
Intervention description(s): 5 po or 2.5 po bid.
Other intervention name(s): eliquis; Coumadin
Intervention MeSH terms: Warfarin; Apixaban
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cardiac Computed tomography; coronary calcification; intervention; warfarin; apixaban