Abstract 10647: Translational Systems Genetics, Electronic Medical Record Analysis, and Molecular Imaging Reveal That the Antidepressant Trazodone Reduces Atherosclerosis as Well as Statins: Drug Discovery by Repurposing of Proven Safe Drugs

Introduction: Statins not infrequently fall short of target reduction in hyperlipidemia. Recently approved anti-lipid drugs are prohibitively expensive. Repurposing previously-approved drugs for new uses in cardiovascular medicine may reduce costs. Hypothesis: Integration of clinical trial data, systems genetics, and real-world evidence from electronic health records may be used to identify drugs with unexpected benefits. Methods: We obtained a gene expression signature from a clinical trial of rosuvastatin, and compared this to in-vitro signatures of 1,309 other compounds. We assayed a lead compound for action on cholesterol biosynthesis in the HepG2 human hepatocyte cellular model. We then used the rabbit model of atherosclerosis (balloon deendothelialization followed by 5-months of high cholesterol/high fat diet) to quantify the necrotic cores of atherosclerotic plaques using molecular imaging with 99mTc-labeled HYNIC-Duramycin (a marker of cell death). We also analyzed lipid levels for patients given ...