Apixaban Versus Warfarin in the Evaluation of Progression of Atherosclerotic Calcification and Vulnerable Plaque
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|ClinicalTrials.gov Identifier: NCT02090075|
Recruitment Status : Completed
First Posted : March 18, 2014
Results First Posted : April 23, 2019
Last Update Posted : April 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation||Drug: apixaban Drug: warfarin||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||66 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Official Title:||Apixaban Versus Warfarin in the Evaluation of Progression of Atherosclerotic Calcification and Vulnerable Plaque|
|Study Start Date :||September 2014|
|Actual Primary Completion Date :||December 27, 2016|
|Actual Study Completion Date :||April 5, 2017|
Active Comparator: apixaban
apixaban 5 mg or 2.5 mg po bid
5 po or 2.5 po bid.
Other Name: eliquis
Placebo Comparator: warfarin
warfarin with target INR of 2-3
Other Name: Coumadin
- Coronary Artery Calcium (CAC) Score [ Time Frame: 1 year ]amount of calcification measured by Agatston Score. The range of values for the Agatston score is 0-10000. Higher score is worse outcome.
- Coronary Plaque on CT Angiography [ Time Frame: 1 year ]To evaluate if treatment with apixaban therapy, as compared to warfarin therapy, will modify the progression, regression and stabilization of coronary atherosclerosis. Modifications will include differences in plaque volume, composition and arterial remodeling; as well as new atherosclerosis formation. The scale is based upon volume of plaque in the coronary arteries, with zero being no plaque and a higher number being more plaque. There is no scale or maximum measure, this is a linear measure of atherosclerosis volume in the coronary arteries and more is worse. None is best, any plaque is considered worse, and a higher plaque volume represents more atherosclerosis. An individual of average health will have a score of 50.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02090075
|United States, California|
|Los Angeles Biomedical Research Institute|
|Torrance, California, United States, 90502|
|Principal Investigator:||Matthew Budoff, MD||Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center|