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OBJECTIVES: The effect of statin therapy on coronary artery calcification is unclear. Early studies suggested a slower rate of coronary artery calcium score (CACS) progression, but recent prospective trials have failed to show this benefit. Recent studies have explored the use of Cardiac Computed Tomography Angiography (CCTA) to characterize plaque features. We provide a systematic review of available literature documenting the effects of statin therapy on the progression of CACS and non-calcium-based indices. METHODS: A systematic search was performed from January 1, 1980 to April 28, 2016 using these databases: Cochrane Database, ACP Journal Club, Health Technology Assessment, Embase, NHS Economic Evaluation Database, Ovid MEDLINE, Health and Psychosocial Instruments. English language publications that serially measured relationships between statin therapy and CACS or noncalcium- based indices were included. Case reports, reviews and meta-analyses were excluded. Data regarding progression of calcium and non-calcium-based indices were extracted and analyzed. RESULTS: 2159 articles were retrieved for screening. Of these, 22 met pre-defined inclusion criteria; 9 were randomized controlled trials and 13 observational studies. Observational studies did not consistently demonstrate a reduction in the progression of CACS with statin therapy. No randomized trial demonstrated convincing evidence that statin therapy reduces the progression of CACS. Limited randomized trials of CCTA suggest that statin therapy may reduce non-calcified plaque volume, but increase dense calcium volume. CONCLUSION: Based on studies using statins, serial assessment of noncalcified plaque volume, but not CACS, may be useful for the assessment of medical interventions with postulated effects on progression or regression of atherosclerosis.