Table 2.

Published studies that used anti-atherosclerotic therapies

Study	Design	Population	Number of participants	Follow-up period	Therapy or comparison	What is measured	Treatment effect*
Burgstahler et al. Invest Radiol. 2007	Prospective interventional	Patients with elevated risk for CAD	27	12 months	Atorvastatin + aspirin	Noncalcified plaque volume	Mean change−0.012 mL; p<0.05 versus baseline
Hoffmann H et al. Eur Radiol 2010	Retrospective observational	Patients with suspected CAD	63	25 ± 3 months	Statins	Noncalcified plaque volume	Plaque growth slowed by statin therapy (p = 0.01)
Inoue K et al. JACC Cardiovasc Imaging. 2010	Prospective interventional controlled	Patients with suspected CAD	32	12 months	Fluvastatin versus control	Total and Low-attenuation plaque volume	Mean change −15.9 versus 4 mm3; p = 0.01,−3.7 versus 0.2 mm3; p<0.01
Tardif JC et al. Circ Cardiovasc Imaging. 2010	Prospective interventional randomized controlled	Patients with MI or unstable angina	93	24 weeks	Atreleuton versus placebo	Noncalcified plaque volume	Mean change −2.33 versus 2.83 mm3; p<0.01
Soeda T et al. Circ J. 2011	Prospective interventional	Patients with ACS	11	24 weeks	Rosuvastatin	Total plaque volume	Mean change −24.7mm3; p = 0.07
Zeb I et al. Atherosclerosis. 2013	Retrospective observational	Patients with no prior heart disease or revascularization	100	406 ± 92 days	Statin versus no statin	Total & Noncalcified plaque volume	Mean change: −33.3 versus 31.0 mm3; p = 0.0006, − 47.7 versus 13.8mm3; p<0.001
Lo J, Lu MT et al. Lancet HIV. 2015	Prospective interventional randomized controlled	People living with HIV	40	12 months	Atorvastatin versus placebo	Noncalcified plaque volume	Median change − 8.2 versus 6.7 mm3; p = 0.03 (−19.4% vs.+ 20.4%; p = 0.009)
Auscher S et al. Atherosclerosis. 2015	Prospective interventional randomized controlled	Patients with acute MI	140	12 months	Intensive statin (Rosuvastatin) versus standard statin	Total plaque volume & dense calcium volume	Mean change 43.5 versus 19.1 mm3; p = 0.57,+ 11.1 versus−0.4 mm3; p< 0.001
Hauser et al. JAMA Cardiol. 2016	Prospective interventional randomized controlled	Patients with CAD	257	30 months	Salsalate versus placebo	Total & Noncalcified plaque volume	Mean change 7 versus 13 mm3; p = 0.35, 0 versus 0 mm3; p = 0.87
Li Z et al. Am Heart J. 2016	Prospective observational	Patients with mild noncalcified plaque	206	18 months	Intensive versus moderate versus no statin	Total & Low-attenuation plaque volume	Mean change − 16.4 versus −0.1 versus 12.3; p<0.001,−7.1 versus −2.8 versus 0.9 mm3; p< 0.001
Matsumoto S et al. J Nutr. 2016	Prospective interventional randomized controlled	Patients with metabolic syndrome	55	354 ±41 days	Aged Garlic Extract versus placebo	Total, Non-calcified and Low-attenuation plaque volume	% change mean Total: 0.3 versus 1.6, p = 0.13; Noncalcified: 0.2 versus 1.4, p = 0.14; LAP: −1.5 versus 0.2, p = 0.0049
Alfaddagh et al. J Aha. 2017	Prospective interventional randomized controlled	Patients with stable CAD on statins	285	30 months	Omega-3 ethyl-ester versus control	Total & Noncalcified plaque volume	% change median 6.5 versus 10.0; p = 0.11,−2.4 versus 4.5; p − 0.14
Budoff Metal. JAMA 2017	Prospective interventional randomized controlled	Older men with low testosterone	170	12 months	Testosterone versus placebo	Total & Noncalcified plaque volume	Least squares Mean change 75 versus 28mm3; p = 0.006, 54 versus 14 mm3; p = 0.003
Lee DH et al. Atherosclerosis. 2017	Prospective interventional randomized controlled	Diabetic patients	40	6 months	Sarpogrelate + aspirin versus aspirin	Total & Noncalcified plaque volume	Mean change −7.8 versus 3.7 mm3; p<0.05,−4.4 versus 1.6 mm3; p<0.01
Matsumoto S et al. Clinical Cardiology 2017	Prospective interventional randomized controlled	Patients with ACS	60	6 months	Atreleuton versus control	Low-attenuation plaque, Fibro-fatty tissue, Fibro-calcified plaque & Dense calcium plaque volume	Mean change LAP − 9.7 versus 5.9 mm3; p<0.05, FF−0.9 versus 11.1 mm3; p<0.05, FC − 14.3 versus − 0.1mm3; p<0.05, DC 0.2 versus 3.9 mm3; p<0.05
Vaidya K et al. JACC Cardiovasc Imaging. 2017	Prospective observational controlled	Patients with ACS	80	12 months	Colchicine + OMT versus OMT	Low-attenuation & Noncalcified plaque volume	Mean change − 15.9 versus −6.6mm3; p = 0.008,−26.3 versus− 18.2mm3; p = 0.62
Lee J et al. Am Heart J. 2018	Prospective interventional randomized	Patients with nonvalvular atrial fibrillation	120	12 months	Warfarin versus Rivaroxaban	Total, Noncalcified & Low-attenuation plaque volume	Median change: 40.5 versus 26.3 mm3; p = 0.123, 30.1 versus 20.1mm3; p = 0.259, 0.2 versus 1.2mm3; p = 0.475
Win T et al. Am Heart J. 2019	Prospective interventional randomized	Patients with nonvalvular atrial fibrillation	66	12 months	Warfarin versus Apixaban	Total, Noncalcified & Low-attenuation plaque volume	Mean change 53.8 versus 46.8 mm3; p = 0.40, 36 versus 31.5 mm3; p = 0.43, 2.3 versus 0.3mm3; p = 0.97
Lee SE et al. Eur Heart J Cardiovasc Imaging. 2019	Retrospective observational	Patients from PARADIGM registry	654	3.9 ± 1.5 years	Statins versus no statins	Total & Noncalcified plaque volume	Annualized change in normalized plaque volumes: 20.2 versus 13.0mm3/year; p< 0.001, 6.4 versus 7.0mm3/year; p = 0.702

We conducted a systematic review using PubMed and ClinicalTrials.gov to identify published and ongoing studies using CCTA to assess therapies’ efficacy in reducing coronary plaque volume untill February 2019. We included studies if they performed serial CCTA to assess the efficacy of anti-atherosclerotic therapies and examined changes in plaque volume. Studies were excluded if (1) the full article was not in English, (2) recruitment status is not yet recruiting, suspended, terminated, withdrawn, or unknown

^*p values given for cohort versus control. If not available, p values given for baseline versus follow-up