The REMBRANDT trial represents a methodological shift in cardiovascular drug evaluation, using coronary computed tomographic angiography to directly measure noncalcified plaque volume changes rather than relying solely on clinical endpoints. This 300-participant study combines obicetrapib, a cholesteryl ester transfer protein inhibitor, with ezetimibe to target LDL cholesterol reduction in patients with established cardiovascular disease. The 18-month imaging protocol offers an unprecedented opportunity to observe real-time arterial changes in response to dual-mechanism cholesterol lowering. This approach could fundamentally alter how we assess cardiovascular interventions, moving beyond traditional surrogate markers like cholesterol levels to direct visualization of disease regression. The trial's focus on patients already receiving maximally tolerated lipid therapy addresses a critical gap for high-risk individuals who remain above target LDL levels. If successful, this imaging-based methodology could accelerate cardiovascular drug development by providing earlier proof-of-concept data. However, the relationship between plaque volume reduction and clinical outcomes remains incompletely understood, and the trial's relatively small size limits its ability to detect safety signals that might emerge in larger populations.