Coronary artery calcium to improve the efficiency of randomized controlled trials in primary cardiovascular prevention
File(s)
Author(s)
Type
Journal Article
Abstract
OBJECTIVES: This study sought to assess the value, in terms of sample size and cost, of using the coronary artery calcium (CAC) score to enrich the study population of primary prevention randomized controlled trials (RCTs) with participants at high absolute risk of atherosclerotic cardiovascular disease (ASCVD) events. BACKGROUND: The feasibility of RCTs assessing the efficacy of novel add-on therapies for primary prevention among high-risk individuals treated with statins may be limited by sample size and cost. METHODS: We evaluated 3,075 statin-naive participants from the Multi-Ethnic Study of Atherosclerosis with estimated 10-year ASCVD risk of ≥7.5%. CAC of >100, CAC of >400, high sensitivity C-reactive protein levels of >2 and >3 mg/l, ankle-brachial index of <0.9, and triglyceride levels of >175 mg/dl were each evaluated as enrichment criteria on top of estimated ASCVD risk of ≥7.5%, ≥10%, ≥15% and ≥20%. For each criterion, using the observed 5-year incidence of CVD, we projected the incidence of CVD assuming a 28% relative risk reduction with high-intensity statin therapy and after addition of novel therapy with additive relative risk reductions of 15% and 25%. Sample size and cost of a hypothetical primary prevention 5-year RCT of a novel therapy on top of statins versus statins alone were then computed by using the projected incidences. Yearly costs per included participant of $6,000 to $9,000 and of $500/$600 per screened nonparticipant were assumed. RESULTS: CAC of >400, present in 15% to 23% participants, consistently identified the subgroups with highest 5-year incident events and outperformed the other features yielding the smallest projected sample size, ranging 33% to 58% lower than using risk estimations alone for participant selection. CAC of >400 also yielded the lowest projected RCT costs, at least $40 million lower than using risk estimations alone. CAC of >100 showed the second-best performance in most scenarios. CONCLUSIONS: High CAC scores used as study entry criteria can improve the efficiency and feasibility of primary prevention RCTs evaluating the incremental efficacy of novel add-on therapies.
Date Issued
2021-05-01
Date Acceptance
2020-10-14
Citation
JACC: Cardiovascular Imaging, 2021, 14 (5), pp.1005-1016
ISSN
1876-7591
Publisher
Elsevier
Start Page
1005
End Page
1016
Journal / Book Title
JACC: Cardiovascular Imaging
Volume
14
Issue
5
Copyright Statement
© 2020 by the American College of Cardiology Foundation. Published by Elsevier. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/33221237
PII: S1936-878X(20)30938-4
Subjects
cardiovascular disease
coronary artery calcium
cost
prevention
randomized controlled trials
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-11-18