Professor Special Lecture: 158th Regular Meeting of the Medical Society of Toho University Effects of Pitavastatin Beyond Cholesterol Reduction: Surprises and Lessons from a Prospective Randomized Open-Label Clinical Trial

Statins (hydroxymethylglutaryl-CoA reductase inhibitors) are used globally in patients with hypercholesterolemia to prevent atherosclerotic diseases. The effectiveness of statins in reducing the number of cardiovascular events depends on the degree to which low-density lipoprotein cholesterol (LDL-C) levels are reduced. In Japan, the three most commonly used moderate-intensity statins are pitavastatin (2 mg/day), atorvastatin (10 mg/day), and rosuvastatin (2.5 mg/day). Until recently, the frequency of cardiovascular events among patients taking these statins had not been explored. We reported the outcomes of patients with hypercholesterolemia treated with either pitavastatin or atorvastatin in the TOHO lipid intervention trial using pitavastatin (TOHO-LIP). In this article, the beneficial effects of pitavastatin beyond cholesterol reduction discovered in the TOHO-LIP+H1:H4 trial are described and a historical backdrop is provided. The subjects were patients with hypercholesterolemia with one or more risk factors for atherosclerosis, randomized to receive either pitavastatin (2 mg/day; n = 332) or atorvastatin (10 mg/day; n = 332). The follow-up period was 240 weeks. The primary composite end point was cardiovascular death, sudden death of unknown origin, nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, or heart failure requiring hospitalization. Patients who received pitavastatin treatment experienced fewer cardiovascular events during the follow-up than those who received atorvastatin treatment, although both statins produced similar effects on LDL-C levels. Subgroup analyses revealed that the cardio-ankle vascular index was significantly lower among patients in the pitavastatin group than in the atorvastatin group. Moreover, the preheparin serum lipoprotein lipase mass level, which correlates negatively with coronary atherosclerosis progression, was higher in the pitavastatin group than in the atorvastatin group. Recently, pitavastatin has been shown to have anticancer effects by inhibiting cell growth. Pitavastatin may similarly inhibit atherosclerosis-related cell growth, thereby reducing rates of cardiovascular events in high-risk patients.