Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry

Curtis Williams, Donghee Han, Hidenobu Takagi, Christopher B. Fordyce, Stephanie Sellers, Philipp Blanke, Fay Y. Lin, Leslee J. Shaw, Sang Eun Lee, Daniele Andreini, Mouaz H. Al-Mallah, Matthew J. Budoff, Filippo Cademartiri, Kavitha Chinnaiyan, Jung Hyun Choi, Edoardo Conte, Hugo Marques, Pedro de Araújo Gonçalves, Ilan Gottlieb, Martin HadamitzkyErica Maffei, Gianluca Pontone, Sanghoon Shin, Yong Jin Kim, Byoung Kwon Lee, Eun Ju Chun, Ji Min Sung, Renu Virmani, Habib Samady, Peter H. Stone, Daniel S. Berman, Jagat Narula, Jeroen J. Bax, Jonathon A. Leipsic, Hyuk Jae Chang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background and aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV. Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

Original languageEnglish (US)
Article number117301
StatePublished - Oct 2023


  • ACE inhibitor
  • Coronary CT angiography
  • Plaque morphology
  • Plaque progression
  • RAAS inhibitor
  • Stable coronary artery disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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