To the Editor The authors of the MDCO-216 Infusions Leading to Changes in Atherosclerosis: a Novel Therapy in Development to Improve Cardiovascular Outcomes—Proof of Concept IVUS, Lipids, and Other Surrogate Biomarkers (MILANO-PILOT) trial1 conclude that there is an uncertainty regarding the therapeutic potential of targeting high-density lipoprotein (HDL). Although we concur that recent studies have not demonstrated positive outcomes with HDL-targeted therapies, this skepticism should not be based on data from this MILANO-PILOT trial.1