BACKGROUND: Coronary atherosclerosis progresses faster in patients with diabetes mellitus (DM) and causes higher morbidity and mortality in such patients compared to non-diabetics ones (non-DM). We quantify changes in plaque volume and plaque phenotype during lipid-lowering therapy in DM versus non-DM patients using advanced intracoronary imaging. METHODS: We analyzed data from 61 patients with stable angina pectoris included to the PREDICT trial searching for prediction of plaque changes during intensive lipid-lowering therapy (40 mg rosuvastatin daily). Geometrically correct, fully 3-D representation of the vascular wall surfaces and intravascular ultrasound virtual histology (IVUS-VH) defined tissue characterization was obtained via fusion of two-plane angiography and IVUS-VH. Frame-based indices of plaque morphology and virtual histology analyses were computed and averaged in 5 mm long baseline/follow-up registered vessel segments covering the entire length of the two sequential pullbacks (baseline, 1-year). We analyzed 698 5-mm-long segments and calculated the Liverpool active plaque score (LAPS). RESULTS: Despite reaching similar levels of LDL cholesterol (DM 2.12 ± 0.91 mmol/l, non-DM 1.8 ± 0.66 mmol/l, p = 0.21), DM patients experienced, compared to non-DM ones, higher progression of mean plaque area (0.47 ± 1.15 mm2 vs. 0.21 ± 0.97, p = 0.001), percent atheroma volume (0.7 ± 2.8% vs. - 1.4 ± 2.5%, p = 0.007), increase of LAPS (0.23 ± 1.66 vs. 0.13 ± 1.79, p = 0.018), and exhibited more locations with TCFA (Thin-Cap Fibro-Atheroma) plaque phenotype in 5 mm vessel segments (20.3% vs. 12.5%, p = 0.01). However, only non-DM patients reached significant decrease of LDL cholesterol. Plaque changes were more pronounced in PIT (pathologic intimal thickening) compared to TCFA with increased plaque area in both phenotypes in DM patients. CONCLUSION: Based on detailed 3D analysis, we found advanced plaque phenotype and further atherosclerosis progression in DM patients despite the same reached levels of LDLc as in non-DM patients. Trial registration ClinicalTrials.gov identifier: NCT01773512.

2nd Department of Medicine Department of Cardiovascular Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague 2 interni klinika VFN a 1 LF UK U nemocnice 2 128 08 Praha 2 Czech Republic

Cardiology Department Na Homolce Hospital Prague Czech Republic

Cardiovascular Research Foundation New York USA

Department of Electrical and Computer Engineering and Iowa Institute for Biomedical Imaging The University of Iowa Iowa City IA USA

Institute for Research and Development of Education Faculty of Education Charles University Prague Prague Czech Republic

Loyola University Stritch School of Medicine Maywood IL USA

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Schartl M, Bocksch W, Koschyk DH, Voelker W, Karsch KR, Kreuzer J, Hausmann D, Backmann S, Gross M. Use of intravascular ultrasound to compare effect of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease. Circulation. 2001;104:387–392. doi: 10.1161/hc2901.093188. PubMed DOI

Nissen SE, Tuzcu EM, Shoenhagen P, Brown BG, Ganz P, Vogel RA, Crowe T, Howard G, Cooper CJ, Brodie B, Grines CL, De Maria AN, REVERSAL Investigators Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–1080. doi: 10.1001/jama.291.9.1071. PubMed DOI

Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–1565. doi: 10.1001/jama.295.13.jpc60002. PubMed DOI

Nozue T, Yamamoto S, Tohyama S, Fukui K, Umezawa S, Onishi Y, Kunishima T, Sato A, Nozato T, Miyake S, Takeyama Y, Morino Y, Yamauchi T, Muramatsu T, Hibi K, Terashima M, Michishita I, for the TRUTH Investigators Impact of diabetes mellitus on coronary atherosclerosis and plaque composition under statin therapy—subanalysis of the truth study. Circ J. 2012;76:2188–2196. doi: 10.1253/circj.CJ-11-1303. PubMed DOI

Kovarnik T, Mintz GS, Skalicka H, Kral A, Horak J, Skulec R, Uhrova J, Martasek P, Downe RW, Wahle A, Sonka M, Mrazek V, Aschermann M, Linhart A. Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study. Circ J. 2012;76:176–183. doi: 10.1253/circj.CJ-11-0730. PubMed DOI

Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M, JAPAN-ACS Investigators Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome] study) J Am Coll Cardiol. 2009;54:293–302. doi: 10.1016/j.jacc.2009.04.033. PubMed DOI

Daida H, Takayama T, Hiro T, Yamagishi M, Hirayama A, Saito S, Yamaguchi T, Matsuzaki M, COSMOS Investigators High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS) Cardiovasc Diabetol. 2012;11:87. doi: 10.1186/1475-2840-11-87. PubMed DOI PMC

Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, Ozaki Y, Kimura K, Saito S, Yamaguchi T, Daida H, Matsuzaki M, JAPAN-ACS Investigators Diabetes mellitus is a major negative determinant of coronary plaque regression during statin therapy in patients with acute coronary syndrome-serial intravascular ultrasound observations from the Japan Assessment of Pitavastatin and Atorvastatin in acute coronary syndrome trial (the JAPAN-ACS Trial) Circ J. 2010;74:1165–1174. doi: 10.1253/circj.CJ-09-0766. PubMed DOI

Bayturan O, Tuzcu EM, Uno K, Lavoie AJ, Hu T, Shreevatsa A, Wolski K, Schoenhagen P, Kapadia S, Nissen SE, Nicholls SJ. Comparison of rates of progression of coronary atherosclerosis in patients with diabetes mellitus versus those with the metabolic syndrome. Am J Cardiol. 2010;105:1735–1739. doi: 10.1016/j.amjcard.2010.01.359. PubMed DOI

Bayturan O, Kapadia S, Nicholls SJ, Tuzcu EM, Shao M, Uno K, Shreevatsa A, Lavoie AJ, Wolski K, Schoenhagen P, Nissen SE. Clinical predictors of plaque progression despite very low levels of low-density lipoprotein cholesterol. J Am Coll Cardiol. 2010;55:2736–2742. doi: 10.1016/j.jacc.2010.01.050. PubMed DOI

Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003;26:2999–3005. doi: 10.2337/diacare.26.11.2999. PubMed DOI

Booth GL, Kapral MK, Fung K, Tu JV. Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study. Lancet. 2006;368:29–36. doi: 10.1016/S0140-6736(06)68967-8. PubMed DOI

Boyle PJ. Diabetes mellitus and macrovascular disease: mechanisms and mediators. Am J Med. 2007;120:S12–S17. doi: 10.1016/j.amjmed.2007.07.003. PubMed DOI

Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234. doi: 10.1056/NEJM199807233390404. PubMed DOI

Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA. 2003;290:1884–1890. doi: 10.1001/jama.290.14.1884. PubMed DOI

Stone GW, Maehara A, Lansky A, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serryus PW. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226–235. doi: 10.1056/NEJMoa1002358. PubMed DOI

Stary HC. Natural history and histological classification of atherosclerotic lesions: an update. Arterioscler Thromb Vasc Biol. 2000;20:1177–1178. doi: 10.1161/01.ATV.20.5.1177. PubMed DOI

Dohi T, Mintz GS, McPherson JA, de Bruyne B, Farhat NZ, Lansky AJ, Mehran R, Weisz G, XU K, Stone GW, Maehara A. Non-fibroatheroma lesion phenotype and long-term clinical outcomes. a substudy analysis from the PROSPECT study. J Am Coll Cardiol Img. 2013;6:908–916. doi: 10.1016/j.jcmg.2013.04.008. PubMed DOI

Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, Erdine S, Halcox J, Hobbs R, Kjekshus J, Filardi PP, Riccardi G, Storey RF, Wood D, European Association for Cardiovascular Prevention & Rehabilitation ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J. 2011;32:1769–1818. doi: 10.1093/eurheartj/ehr158. PubMed DOI

Li K, Wu X, Chen DZ, Sonka M. Optimal surface segmentation in volumetric images-a graph-theoretic approach. IEEE Trans Pattern Anal Mach Intell. 2006;28:119–134. doi: 10.1109/TPAMI.2006.19. PubMed DOI PMC

Yin Y, Zhang X, Williams R, Wu X, Anderson DD, Sonka M. LOGISMOS–layered optimal graph image segmentation of multiple objects and surfaces: cartilage segmentation in the knee joint. IEEE Trans Med Imaging. 2010;29:2023–2037. doi: 10.1109/TMI.2010.2058861. PubMed DOI PMC

Sun S, Sonka M, Beichel RR. Graph-based IVUS segmentation with efficient computer-aided refinement. IEEE Trans Med Imaging. 2013;32:1536–1549. doi: 10.1109/TMI.2013.2260763. PubMed DOI PMC

Wahle A, Prause PM, DeJong SC, Sonka M. Geometrically correct 3D reconstruction of intravascular ultrasound images by fusion with biplane angiography—methods and validation. IEEE Trans Med Imaging. 1999;18:686–699. doi: 10.1109/42.796282. PubMed DOI

Wahle A, Olszewski ME, Vigmostad SC, Medina R, Coskun AU, Feldman C, Stone PH, Braddy KC, Brennan TMH, Rossen JD, Chandran KB, Sonka M. Quantitative analysis of circumferential plaque distribution in human coronary arteries in relation to local vessel curvature. In: IEEE international symposium on biomedical imaging: nano to macro, 2004. New York: IEEE. p. 531–4

García-García HM, Mintz GS, Lerman A, Vince GD, Margolis PMD, van Es GA, More MA, Nair N, Virmani R, Burke AP, Stone GWMD, Serruys PW. Tissue characterization using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. EuroIntervention. 2009;5:177–189. doi: 10.4244/EIJV5I2A29. PubMed DOI

Murray SW, Stables RH, Garcia-Garcia HM, Grayson AD, Shaw MA, Perry RA, Serruys PW, Palmer ND. Construction and validation of a plaque discrimination score from the anatomical and histological differences in coronary atherosclerosis: the Liverpool IVUS-V-HEART (Intra Vascular UltraSound-Virtual-Histology Evaluation of Atherosclerosis Requiring Treatment) study. EuroIntervention. 2014;10:815–823. doi: 10.4244/EIJV10I7A141. PubMed DOI

Burke AP, Kolodgie FD, Zieske A, Fowler DR, Weber DK, Varghese PJ, Farb A, Virmani R. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol. 2004;24:1266–1271. doi: 10.1161/01.ATV.0000131783.74034.97. PubMed DOI

Yang DJ, Lee MS, Kim WH, Park HW, Kim KH, Kwon TG, Kim SW, Rihal CS, Lerman A, Bae JH. The impact of glucose control on coronary plaque composition in patients with diabetes mellitus. J Invasive Cardiol. 2013;25:137–141. PubMed

García-García HM, Serruys PW, Mintz GS, Saito S, Klaus V, Margolis P, Carlier S, Goedhart D, Schwartz R. Synergistic effect of cardiovascular risk factors on necrotic core in coronary arteries: a report from the global intravascular radiofrequency data analysis registry. JACC Cardiovasc Imaging. 2009;2:629–636. doi: 10.1016/j.jcmg.2009.01.008. PubMed DOI

Hong YJ, Jeong MH, Choi YH, Ko JS, Lee MG, Kang WY, Lee SE, Kim SH, Park KH, Sim DS, Yoon NS, Yoon HJ, Kim KH, Park HW, Kim JH, Ahn Y, Cho JG, Park JC, Kang JC. Plaque characteristics in culprit lesions and inflammatory status in diabetic acute coronary syndrome patients. JACC Cardiovasc Imaging. 2009;2:339–349. doi: 10.1016/j.jcmg.2008.10.017. PubMed DOI

Marso SP, House JA, Klauss V, Lerman A, Margolis P, Leon MB, Global VH-IVUS Diabetes mellitus is associated with plaque classified as thin cap fibroatheroma: an intravascular ultrasound study. Diab Vasc Dis Res. 2010;7:14–19. doi: 10.1177/1479164109346764. PubMed DOI

Araki T, Nakamura M, Utsunomiya M, Sugi K. Visualization of coronary plaque in type 2 diabetes mellitus patients using a new 40 MHz intravascular ultrasound imaging system. J Cardiol. 2012;59:42–49. doi: 10.1016/j.jjcc.2011.07.012. PubMed DOI

Kennedy MW, Kaplan E, Hermanides RS, Fabris E, Hemradj V, Koopmans PC, Dambrink JH, Marcel Gosselink AT, Van’t Hof AW, Ottervanger JP, Roolvink V, Remkes WS, van der Sluis A, Suryapranata H, Kedhi E. Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus. Cardiovasc Diabetol. 2016;19(15):100. doi: 10.1186/s12933-016-0417-2. PubMed DOI PMC

Kennedy MW, Hermanides RS, Kaplan E, Hemradj V, Fabris E, Koopmans PC, Dambrink JE, Gosselink AT, Van’t Hof AW, Ottervanger JP, Roolvink V, Remkes WS, van der Sluis A, Suryapranata H, Kedhi E. Fractional flow reserve-guided deferred versus complete revascularization in patients with diabetes mellitus. Am J Cardiol. 2016;118:1293–1299. doi: 10.1016/j.amjcard.2016.07.059. PubMed DOI

Purushothaman KR, Purushothaman M, Muntner P, Lento PA, O’Connor WN, Sharma SK, Fuster V, Moreno PR. Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagencontent: implication for plaque progression in diabetic atherosclerosis. Vasc Med. 2011;16:103–108. doi: 10.1177/1358863X11402249. PubMed DOI

Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46:937–954. doi: 10.1016/j.jacc.2005.03.074. PubMed DOI

Nesto RW, Zarich S. Acute myocardial infarction in diabetes mellitus: lessons learned from ACE inhibition. Circulation. 1998;97:12–15. doi: 10.1161/01.CIR.97.1.12. PubMed DOI

Kim SH, Moon JY, Lim YM, Kim KH, Yang WI, Sung JH, Yoo SM, Kim IJ, Lim SW, Cha DH, Cho SY. Association of insulin resistance and coronary artery remodeling: an intravascular ultrasound study. Cardiovasc Diabetol. 2015;14:74. doi: 10.1186/s12933-015-0238-8. PubMed DOI PMC

Virmani R, Kolodgie FD, Burke AP, Finn AV, Gold HK, Tulenko TN, Wrenn SP, Narula J. Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol. 2005;25:2054–2061. doi: 10.1161/01.ATV.0000178991.71605.18. PubMed DOI

Inaba S, Okayama H, Funada J, Higashi H, Saito M, Yoshii T, Hiasa G, Sumimoto T, Takata Y, Nishimura K, Inoue K, Ogimoto A, Higaki J. Impact of type 2 diabetes on serial changes in tissue characteristics of coronary plaques: an integrated backscatter intravascular ultrasound analysis. Eur Heart J Cardiovasc Imaging. 2012;13:717–723. doi: 10.1093/ehjci/jes033. PubMed DOI

Kawasaki M, Sano K, Okubo M, Yokoyama H, Ito Y, Murata I, Tsuchiya K, Minatoguchi S, Zhou X, Fujita H, Fujiwara H. Volumetric quantitative analysis of tissue characteristics of coronary plaques after statin therapy using three-dimensional integrated backscatter intravascular ultrasound. J Am Coll Cardiol. 2005;45:1946–1953. doi: 10.1016/j.jacc.2004.09.081. PubMed DOI

Kwon O, Kang SJ, Kang SH, Lee PH, Yun SC, Ahn JM, Park DW, Lee SW, Kim YH, Lee CW, Han KH, Park SW, Park SJ. Relationship between serum inflammatory marker levels and the dynamic changes in coronary plaque characteristics after statin therapy. Circ Cardiovasc Imaging. 2017;10:e005934. doi: 10.1161/CIRCIMAGING.116.005934. PubMed DOI

Okada K, Hibi K, Gohbara M, Kataoka S, Takano K, Akiyama E, Matsuzawa Y, Saka K, Maejima N, Endo M, Iwahashi N, Tsukahara K, Kosuge M, Ebina T, Fitzgerald PJ, Honda Y, Umemura S, Kimura K. Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes. Cardiovasc Diabetol. 2015;14:111. doi: 10.1186/s12933-015-0275-3. PubMed DOI PMC

Yoshida N, Yamamoto H, Shinke T, Otake H, Kuroda M, Terashita D, Takahashi H, Sakaguchi K, Hirota Y, Emoto T, Amin HZ, Mizoguchi T, Hayashi T, Sasaki N, Yamashita T, Ogawa W, Hirata K. Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study. Cardiovasc Diabetol. 2017;16:96. doi: 10.1186/s12933-017-0577-8. PubMed DOI PMC

Calvert P, Obaid D, O’Sullivan M, Shapiro L, McNab D, Densem C, Schofield P, Braganza D, Clarke S, Ray K, West N, Bennett M. Association between IVUS findings and adverse outcomes in patients with coronary artery disease the VIVA (VH-IVUS in Vulnerable Atherosclerosis) study. J Am Coll Cardiol Img. 2011;4:894–901. doi: 10.1016/j.jcmg.2011.05.005. PubMed DOI

Pundziute G, Schuijf JD, Jukema JW, van Werkhoven JM, Nucifora G, Decramer I, Sarno G, Vanhoenacker PK, Reiber JH, Wijns W, Bax JJ. Type 2 diabetes is associated with more advanced coronary atherosclerosis on multislice computed tomography and virtual histology intravascular ultrasound. J Nucl Cardiol. 2009;16:376–383. doi: 10.1007/s12350-008-9046-9. PubMed DOI

Nasu K, Tsuchikane E, Katoh O, Fujita H, Surmely JF, Ehara M, Kinoshita Y, Tanaka N, Matsubara T, Asakura Y, Asakura K, Terashima M, Suzuki T. Plaque characterisation by virtual histology intravascular ultrasound analysis in patients with type 2 diabetes. Heart. 2008;94:429–433. doi: 10.1136/hrt.2007.118950. PubMed DOI

Kato K, Yonetsu T, Kim SJ, Xing L, Lee H, McNulty I, Yeh RW, Sakhuja R, Zhang S, Uemura S, Yu B, Mizuno K, Jang IK. Comparison of nonculprit coronary plaque characteristics between patients with and without diabetes: a 3-vessel optical coherence tomography study. JACC Cardiovasc Interv. 2012;5(11):1150–1158. doi: 10.1016/j.jcin.2012.06.019. PubMed DOI

Niccoli G, Giubilato S, Di Vito L, Leo A, Cosentino N, Pitocco D, Marco V, Ghirlanda G, Prati F, Crea F. Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox. Eur Heart J. 2013;34:729–741. doi: 10.1093/eurheartj/ehs393. PubMed DOI

Goderie T, van Soest G, Garcia-Garcia H, Gonzalo N, Koljenovi S, van Leenders G, Mastik F, Regar E, Oosterhuis J, Serruys P, van der Steen A. Combined optical coherence tomography and intravascular ultrasound radio frequency data analysis for plaque characterization. Classification accuracy of human coronary plaques in vitro. Int J Cardiovasc Imaging. 2010;26:843–850. doi: 10.1007/s10554-010-9631-2. PubMed DOI PMC

Roleder T, Kovacic J, Ali Z, Sharma R, Cristea E, Moreno P, Sharma S, Narula J, Kini A. Combined NIRS and IVUS imaging detects vulnerable plaque using a single catheter system: a head-to-head comparison with OCT. EuroIntervention. 2014;10:303–311. doi: 10.4244/EIJV10I3A53. PubMed DOI

Kubo T, Maehara A, Mintz GS, Doi H, Tsujita K, Choi SY, Katoh O, Nasu K, Koenig A, Pieper M, Rogers JH, Wijns W, Bose D, Margolis MP, Moses JW, Stone GW, Leon MB. The dynamic nature of coronary artery lesion morphology assessed by serial virtual histology intravascular ultrasound tissue characterization. J Am Coll Cardiol. 2010;55:1590–1597. doi: 10.1016/j.jacc.2009.07.078. PubMed DOI

Zhao Z, Witzenbichler B, Mintz GS, Jaster M, Choi SY, Wu X, He Y, Margolis MP, Dressler O, Cristea E, Parise H, Mehran R, Stone GW, Maehara A. Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial. JACC Cardiovasc Imaging. 2013;6:86–95. doi: 10.1016/j.jcmg.2012.08.010. PubMed DOI

Lindsey JB, House JA, Kennedy KF, Marso SP. Diabetes duration is associated with increased thin-cap fibroatheroma detected by intravascular ultrasound with virtual histology. Circ Cardiovasc Interv. 2009;2:543–548. doi: 10.1161/CIRCINTERVENTIONS.109.876672. PubMed DOI

Kedhi E, Kennedy MW, Maehara A, Lansky AJ, McAndrew TC, Marso SP, De Bruyne B, Serruys PW, Stone GW. Impact of TCFA on unanticipated ischemic events in medically treated diabetes mellitus: insights from the PROSPECT study. JACC Cardiovasc Imaging. 2017;10:451–458. doi: 10.1016/j.jcmg.2015.12.023. PubMed DOI

Hwang DS, Shin ES, Kim SJ, Lee JH, Kim JM, Lee SG. Early differential changes in coronary plaque composition according to plaque stability following statin initiation in acute coronary syndrome: classification and analysis by intravascular ultrasound-virtual histology. Yonsei Med J. 2013;54:336–344. doi: 10.3349/ymj.2013.54.2.336. PubMed DOI PMC

Cannon Ch, Blazing M, Giugliano R, McCagg A, White J, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–2397. doi: 10.1056/NEJMoa1410489. PubMed DOI

Nicholls S, Puri R, Anderson T, Ballantyne Ch, Cho L, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the glagov randomized clinical trial. JAMA. 2016;316:2373–2384. doi: 10.1001/jama.2016.16951. PubMed DOI

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ClinicalTrials.gov
NCT01773512