To the Editor: Hypoxia-inducible factor (HIF) stabilizers are approved to treat anemia of chronic kidney disease in different regions of the world. However, regulatory agencies have raised concerns regarding their cardiovascular safety. A puzzling observation is that the safety signal from HIF stabilizers with respect to major adverse cardiovascular events (MACE) has ranged from potential protection to neutral to potential harm in diverse clinical trials, even for the same agent, without a clear explanation.1,2 The recent trials of daprodustat (ASCEND-ND [Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat–Non-Dialysis] and ASCEND-D [Anemia Studies in Chronic . . .