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Introduction: Coronary CT angiography (CTA) derived fractional flow reserve (FFR CT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated., Aim: To test whether lipid lowering therapy is associated with significant improvement in FFR CT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery., Methods: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFR CT  ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFR CT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFR CT using (1) the FFR CT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study., Conclusion: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)