Encouragement of Super-aggressive LDL-lowering Therapies

Clinical usefulness of aggressive LDL-lowering therapies using statin, ezetimibe, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have been shown in primary as well as in secondary prevention settings. In addition, the idea that the lower, the better story in LDL appears to be true as low as ~30 mg/dl based on recent randomized controlled trials (RCT). Moreover, aggressive LDL-lowering therapies, for either of primary prevention setting, or secondary prevention setting has been shown to be quite effective in Japanese population as well. According to those facts, recent guidelines in Europe, and in Japan suggest to lower LDL cholesterol (LDL-C) level < 70 mg/dl for high-risk patients. However, the attainment rates of such “strict” goals seem to be quite low, probably because most cardiologists still have a feeling of anxiety of extremely low LDL-C level. In this review article, we provide the idea that LDL-C is one of the well-established causal factors for atherosclerotic cardiovascular disease (ASCVD) based on the findings from Mendelian randomization studies in addition to RCT. The beautiful consistency between RCT and Mendel randomization studies have reassured us that the lower, the better, as well as the earlier, the better appear to be true.