Cryotherapy proved safe for vulnerable coronary plaque stabilization in an preliminary analysis of the POLARSTAR study, with early signs of plaque volume reduction and a positive impact on epicardial conductance. The trial marks the first-in-human (FIH) application of intracoronary cryotherapy for the stabilization of high-risk plaques, building on preclinical evidence that the technique could be beneficial. The preliminary results from the first 10 patients in the trial were presented Sunday in a late-breaking out of the box studies session at Cardiovascular Research Technologies (CRT) 2025 by Carlos Collet, MD, from Olv Hospital Aalst, Belgium. According to its ClinicalTrials.Gov record, the prospective, single-arm study — which tests Cryotherapeutics SA’s CryoTherapy System (CTS) — is expected to enroll a total of 30 patients with acute coronary syndromes (ST segment elevation myocardial infarction [STEMI], non-STEMI, or unstable angina) and a high-risk non-obstructive plaque in a non-culprit vessel. Recruitment is ongoing in 5 sites across Lithuania and Georgia. The coronary cryotherapy system involves deployment of a rapid-exchange balloon-based technology that delivers nitric oxide, reaching temperatures of -20 degrees Celsius at the level of the lesion, Dr. Collet explained. For patients in the preliminary analysis, patients were screened for high-risk plaques using coronary computed tomography (CT) angiography (CCTA) following successful percutaneous coronary intervention (PCI) of the culprit lesion. Cryotherapy guided by intravascular ultrasound (IVUS) was then applied for those with positive results, and patients were followed non-invasively with CCTA at 3 and 9 months. At baseline, the mean age of the first 10 patients was 63.2 ± 10.5 years, and 70% were male. Of the target lesions, 30% were in the left anterior descending artery, 40% in the left circumflex artery, and 30% in the right coronary artery. Clinical presentations included unstable angina (80% of patients) and non-STEMI (20%). In qualitative comparative analysis, the mean diameter stenosis was 39 ± 9% and the reference vessel diameter was 2.9 ± 0.5 mm, Dr. Collet noted, while in IVUS, the Minimal Lumen Aera was 3.6 ± 0.6 mm² and the mean plaque burden was 70 ± 8%. The primary endpoint was the occurrence of any cryotherapy procedure-related complication or any major adverse cardiovascular events (MACE) at 90 days. No procedural complications were reported, but the cryo-balloon was unable to cross the lesion in one case. No adverse MACE were reported at 90 days, and a trend towards reduction in plaque volume (relative change -11% ± 39%) was observed in the 5 patients who had completed the 9-month CCTA follow-up by the time the study report was written. A trend toward a reduction of trans-lesional gradient was also seen in these 5 patients, with a change in trans-lesional fractional flow reserve CT of - 0.02 (interquartile range: -0.13 to 0.0). “In this preliminary report of the POLARSTAR FIH study, the application of cryotherapy for vulnerable plaque stabilization was safe. CCTA results showed a trend towards a reduction in plaque volume with a positive impact on epicardial conductance,” he concluded. Image Credit: Bailey G. Salimes Image Caption: Carlos Collet, MD, presents during the late-breaking out of the box studies session at Cardiovascular Research Technologies (CRT) 2025 on Sunday.