Coronary computed tomography angiography (CTA) plaque imaging could serve as a surrogate biomarker to improve the efficiency and cost-effectiveness of drug development for coronary artery disease (CAD), say researchers. The review, published in the August issue of JACC: Cardiovascular Imaging, puts forward this approach in light of current clinical trials over reliance on major adverse cardiovascular events (MACE) as the gold standard endpoint. The multinational research team argues that the process is too slow and expensive for sustainable innovation. “Despite the robustness of MACE as a primary endpoint for approvals, the associated financial burden consistently runs into the hundreds of millions of dollars for each new drug entity,” wrote the paper’s authors. “Combined with the long timelines and the low likelihood of success in research translation, this has reduced incentives for the pharmacological industry to invest in new cardiovascular research.” Surrogate endpoints Led by Lohendran Baskaran, MBBS, from the National Heart Centre in Singapore, the team highlighted how cancer and other specialties have accelerated drug approvals using imaging-based surrogate endpoints. Coronary CTA, which can noninvasively detect vulnerable plaques in the arteries, may offer a similar opportunity for cardiology. “Coronary CTA uniquely enables detailed noninvasive assessment of coronary plaque, including both morphological characterization and quantification of plaque burden and various plaque components,” the authors wrote. “Given its wide availability, high spatial resolution, and robust validation against intravascular imaging, coronary CTA plaque imaging is arguably the leading noninvasive modality to confer a reliable surrogate endpoint.” The review identified noncalcified plaque volume (NCPV) and low-attenuation plaque volume (LAPV) as exhibiting the strongest associations with future cardiac events and responsiveness to treatment, especially anti-inflammatory agents and statins. “Quantitative plaque markers are preferred over qualitative features, with NCPV and LAPV showing the strongest mechanistic links to MACE and MACE-reducing interventions,” the authors noted. “NCPV has higher reproducibility than does LAPV, making it more suitable as a surrogate biomarker.” Coordinated efforts The review also called for renewed efforts in coordinating global efforts among researchers, regulators and industry stakeholders to standardize and validate these plaque imaging metrics. A new initiative, the ACTION A2D2 consortium, is already working with the U.S. FDA to explore NCPV as a potential regulatory endpoint. If validated, coronary CTA–based plaque markers could dramatically reduce trial size and duration. “[These surrogate endpoints] offer several potential benefits for future cardiovascular research trials, ultimately facilitating clinical translation of cardiovascular drugs and improving patient outcomes,” the review concluded. Sources: Baskaran L, Dutta U, Wang X, et al. Accelerating Drug Translation: Role of Coronary Computed Tomography Angiography Plaque Imaging Candidates as Surrogate Biomarkers. JACC Cardiovasc Imaging. 2025;18:912–927. Image Credit: Nuttapong punna – stock.adobe.com