Lipid Burden and Efficacy of Preventive PCI of Vulnerable Atherosclerotic Coronary Plaques: Post Hoc Analysis From the PREVENT Trial

BACKGROUND: Preventive percutaneous coronary intervention (PCI) of non–flow-limiting lesions (fractional flow reserve >0.80) that are high-risk plaques has emerged as a potential strategy to reduce cardiac events. However, identifying which lesions derive the greatest benefit from preventive PCI compared with optimal medical therapy alone remains challenging. This post hoc analysis evaluates the role of the near-infrared spectroscopy–derived lipid core burden index in identifying high-risk plaques that may benefit from preventive PCI. METHODS: Among the 1606 patients enrolled in the PREVENT trial (Preventive Coronary Intervention on Stenosis with Functionally Insignificant Vulnerable Plaque) from September 2015 to September 2021, an investigator-initiated, multicenter, open-label, randomized controlled trial, this post hoc analysis included 598 patients (mean age, 64.1±8.8 years; 27.9% women) comprising 632 lesions with a plaque burden >70% and a minimal lumen area <4 mm 2 by intravascular ultrasound in whom near-infrared spectroscopy evaluation was also performed. Lipid-rich plaque (LRP) was prespecified as having a maximum lipid core burden index over a 4-mm segment >315. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischemia-driven target-vessel revascularization, or hospitalization for unstable or progressive angina. RESULTS: LRPs were present in 223 patients (37.3%) with 234 lesions. During median follow-up of 5.6 years, primary outcome events occurred more frequently in patients with LRPs than in those with non-LRPs (12.5% versus 4.7%; unadjusted hazard ratio, 2.08; 95% CI, 1.03–4.19; P =0.039) in the overall population. Within the LRP group, preventive PCI was associated with a lower risk of the primary outcome compared with optimal medical therapy alone (7.3% vs. 17.6%; adjusted hazard ratio, 0.23; 95% CI, 0.13–0.41; P <0.001). Conversely, no benefit of preventive PCI was observed in the non-LRP group (5.5% versus 4.2%; adjusted hazard ratio, 1.00; 95% CI, 0.54–1.86; P =0.97). A significant interaction was found between treatment strategy and the presence of LRP ( P interaction <0.001). CONCLUSIONS: In this post hoc analysis of the PREVENT trial, preventive PCI was associated with a lower risk of the primary composite outcome in patients with near-infrared spectroscopy–defined LRPs, whereas no significant association was observed in those with non-LRPs despite their large plaque burden and small minimal lumen area. These findings suggest the importance of plaque composition, beyond morphological severity alone, in guiding preventive PCI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02316886.