Effects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study

Sang Eun Lee, Hyuk Jae Chang, Ji Min Sung, Hyung Bok Park, Ran Heo, Asim Rizvi, Fay Y. Lin, Amit Kumar, Martin Hadamitzky, Yong Jin Kim, Edoardo Conte, Daniele Andreini, Gianluca Pontone, Matthew J. Budoff, Ilan Gottlieb, Byoung Kwon Lee, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo MarquesJonathon A. Leipsic, Sanghoon Shin, Jung Hyun Choi, Kavitha Chinnaiyan, Gilbert Raff, Renu Virmani, Habib Samady, Peter H. Stone, Daniel S. Berman, Jagat Narula, Leslee J. Shaw, Jeroen J. Bax, James K. Min

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

Objectives: This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. Background: Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. Methods: We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. Results: Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. Conclusions: Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)

Original languageEnglish
Pages (from-to)1475-1484
Number of pages10
JournalJACC: Cardiovascular Imaging
Volume11
Issue number10
DOIs
Publication statusPublished - 2018 Oct

Bibliographical note

Funding Information:
Supported in part by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea, funded by Ministry of Science and ICT (MSIT) grant 2012027176 and by gifts from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. Funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang had full access to all data in the study and final responsibility for the decision to submit the manuscript for publication. Dr. Chang has received funding from Leading Foreign Research Institute Recruitment Program through NRF of Korea funded by MSIT grant 2012027176). Dr. Min has received funding from U.S. National Institutes of Health (NIH) grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907, Qatar National Priorities Research Program grant 09-370-3-089, and GE Healthcare. Dr. Min has consulted for HeartFlow; has served on the scientific advisory board of Arineta; and holds equity interest in MDDX. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Chun has received funding from NRF grant NRF-2015R1D1A1A01059717, funded by the Korean Government (Ministry of Education, Science and Technology [MEST]). Dr. Leipsic has consulted for and holds stock in HeartFlow and Circle Cardiovascular Imaging; and has received speakers fees from GE Healthcare. Dr. Budoff has received grants from NIH and GE Healthcare. Dr. Samady has received grant support from Phillips/Volcano and St. Jude and Abbott, Medtronic, and Gilead. Dr. Andreini is a member of the speakers bureau for GE Healthcare; and has received grant support from GE Healthcare and Bracco. Dr. Pontone has received institutional research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Berman has received royalties from Cedars-Sinai. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, Arterial Remodeling Technologies (ART) BioSensors International, Biotronik, Boston Scientific, Celonova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; and has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and has consulted for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Todd Villines, MD, served as the Guest Editor for this paper.

Publisher Copyright:
© 2018 American College of Cardiology Foundation

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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