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Randomized Controlled Trial
. 2025 Apr 22;333(16):1403-1412.
doi: 10.1001/jama.2025.0584.

Effects of Combining Coronary Calcium Score With Treatment on Plaque Progression in Familial Coronary Artery Disease: A Randomized Clinical Trial

Nitesh Nerlekar  1   2   3 , Sheran A Vasanthakumar  2 , Kristyn Whitmore  1   4 , Cheng Hwee Soh  1 , Jasmine Chan  2 , Vinay Goel  2 , Jacqueline Ryan  5 , Catherine Jones  6 , Tony Stanton  7 , Geoffrey Mitchell  8 , Andrew Tonkin  9 , Gerald F Watts  5 , Stephen J Nicholls  2   3   9 , Thomas H Marwick  1   4   10 ; Coronary Artery Calcium Score: Use to Guide Management of Hereditary Coronary Artery Disease (CAUGHT-CAD) Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Effects of Combining Coronary Calcium Score With Treatment on Plaque Progression in Familial Coronary Artery Disease: A Randomized Clinical Trial

Nitesh Nerlekar et al. JAMA. .

Abstract

Importance: Coronary artery calcium (CAC) scoring provides prognostic information, especially in patients at intermediate risk for coronary artery disease (CAD). However, the benefit of combining CAC score with a primary prevention strategy has not been tested in a randomized trial.

Objective: To assess whether combining the CAC score with a prevention strategy can be used to limit plaque progression in intermediate-risk patients with a family history of premature CAD.

Design, setting, and participants: Prospective, randomized, open-blinded end point clinical trial in 7 hospitals across Australia (between 2013 and 2020; the last date of follow-up was June 5, 2021). Asymptomatic people aged 40 to 70 years with a first-degree relative with CAD onset at younger than 60 years old or second-degree relative with onset at younger than 50 years old were recruited from the community.

Interventions: Intermediate-risk participants underwent CAC scoring. Those with a CAC score greater than 0 but less than 400 underwent coronary computed tomography angiography (CCTA) and were randomized to CAC score-informed prevention or usual care.

Main outcomes and measures: Follow-up CCTA was obtained at 3 years, with plaque volume measured by an independent core laboratory. The primary outcome was total plaque volume, with further analysis for calcified and noncalcified plaque volume.

Results: This study included 365 participants (mean [SD] age, 58 [6] years; 57.5% male); 179 in the CAC score-informed and 186 in the usual care groups. Compared with usual care, the CAC score-informed group showed a sustained reduction in total (mean [SD], -3 [31] mg/dL vs -56 [38] mg/dL; P < .001) and LDL (mean [SD], -2 [31] vs -51 [36] mg/dL; P < .001) cholesterol levels at 3 years, which was associated with a reduction in pooled cohort equation risk calculation (mean [SD], 2.1% [2.9%] vs 0.5% [2.9%]; P < .001). Plaque progression was greater in usual care than CAC score-informed participants for total plaque volume (mean [SD], 24.9 [37.7] mm3 vs 15.4 [30.9] mm3; P = .009), noncalcified plaque volume (mean [SD], 15.7 [32.2] mm3 vs 5.6 [28.5] mm3; P = .002), and fibrofatty and necrotic core plaque volume (mean [SD], 4.5 [25.8] mm3 vs -0.8 [12.6] mm3; P = .02). These plaque volume changes were independent of other risk factors including baseline plaque volume, blood pressure, and lipid profile.

Conclusions and relevance: The combination of CAC score with a primary prevention strategy in intermediate-risk patients with a family history of CAD was associated with reduction of atherogenic lipids and slower plaque progression compared with usual care. These data support the use of CAC score to assist intensive preventive strategies in intermediate-risk patients.

Trial registration: anzctr.org.au Identifier: ACTRN12614001294640.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nerlekar reported receiving nonfinancial support from CureMetrix outside the submitted work. Dr Goel reported receiving personal fees from CureMetrix Inc outside the submitted work. Dr Tonkin reported receiving personal fees from Novartis and Amgen and being a member of the data monitoring committee of the ORION-4 study outside the submitted work. Dr Watts reported receiving personal fees from Amgen, Arrowhead, Novartis, Novo Nordisk, and GSK and grants from Amgen, Arrowhead, and Novartis outside the submitted work. Dr Nicholls reported receiving grants from AstraZeneca, NewAmsterdam Pharma, Amgen, Anthera, Cyclarity, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, Infraredx, Roche, Sanofi-Regeneron, and LipoScience paid to institution and personal fees from Abcentra, AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Daiichi Sankyo, Silence Therapeutics, CSL Seqirus, and Vaxxinity during the conduct of the study; in addition, Dr Nicholls had a patent for proprotein convertase subtilisin/kexin type 9 inhibitor and atherosclerosis issued but received no royalties. Dr Marwick reported nonfinancial support from GE Medical Systems and grants from AstraZeneca outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Recruitment, Randomization, and Follow-Up in the CAUGHT-CAD Trial
CAC indicates coronary artery calcium; CAD, coronary artery disease; CAUGHT-CAD, Coronary Artery Calcium Score: Use to Guide Management of Hereditary Coronary Artery Disease; and LDL-C, low-density lipoprotein cholesterol. To convert cholesterol to mmol/L, multiply by 0.0259.
Figure 2.
Figure 2.. Longitudinal Change in Plaque Volume Between Coronary Artery Calcium (CAC) Score–Informed and Usual Care Participants
Violin plot of data demonstrates the comparison of Δ plaque volumes between CAC score–informed and usual care and individuals. Each violin represents a density curve of the complete distribution of data within each group. The width corresponds with the approximate frequency of data points in each region. The median value is represented by the horizontal dashed red line and the white lines indicate IQRs. See Table 3 for detailed plaque values and Δ differences.
Figure 3.
Figure 3.. Examples of Plaque Volume Change
A, Panels demonstrate plaque regression with resolution of higher-risk plaque features of necrotic core and fibrofatty plaque with transformation to more fibrous phenotype. B, Panels demonstrate new plaque lesion formation with higher-risk plaque morphology and extension of the overall lesion length in the longitudinal plane.
See this image and copyright information in PMC

Comment in

References

    1. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898-904. doi: 10.1001/jama.290.7.898 - DOI - PubMed
    1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25):2889-2934. doi: 10.1016/j.jacc.2013.11.002 - DOI - PubMed
    1. Lloyd-Jones DM, Nam BH, D’Agostino RB Sr, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA. 2004;291(18):2204-2211. doi: 10.1001/jama.291.18.2204 - DOI - PubMed
    1. Nasir K, Budoff MJ, Wong ND, et al. Family history of premature coronary heart disease and coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2007;116(6):619-626. doi: 10.1161/CIRCULATIONAHA.107.688739 - DOI - PubMed
    1. Bachmann JM, Willis BL, Ayers CR, Khera A, Berry JD. Association between family history and coronary heart disease death across long-term follow-up in men: the Cooper Center Longitudinal Study. Circulation. 2012;125(25):3092-3098. doi: 10.1161/CIRCULATIONAHA.111.065490 - DOI - PMC - PubMed

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