Ezetimibe is a new class of selective cholesterol absorption inhibitors that bind to small intestine brush-like membranous membrane vesicular membrane protein (relative molecular mass of 145X103) to inhibit the small intestine from feeding to and feeding through the bile into the intestine Of cholesterol absorption, lower serum and liver cholesterol levels. Unlike cholic acid chelating agents, ezetimibe does not affect the absorption of cholesterol esters, other steroids (such as bovine cholic acid), triglyceride and fat-soluble vitamins. The pharmacological effects were not related to the inhibition of acetyl-CoA-cholesterol acetyltransferase (ACAT) and the expression of LDL receptor (scavenger receptor). Ezetimibe is absorbed in the liver after binding to glucuronic acid by the hepatic and intestinal circulation, almost specifically located in the small intestinal mucosal cells.
BACKGROUND: Statins have reduced the risk of low-density lipoprotein (LDL) cholesterol and cardiovascular events, but the addition of ezetimibe (a class of non-statins that reduce intestinal cholesterol absorption) can further reduce the incidence of cardiovascular events The rate is still unclear.
METHODS: The investigators conducted a double-blind, randomized trial of 18144 patients with acute coronary syndromes. In these patients, the LDL cholesterol level for lipid-lowering therapy was 50-100 mg / dl (1.3-2.6 mmol / L) and LDL cholesterol levels without lipid-lowering therapy were 50-125 mg / dl (1.3-3.2 mmol / L ). A study was conducted for simvastatin (40 mg) + ezetimibe (10 mg) (simvastatin-ezetimibe) and simvastatin (40 mg) + placebo (simvastatin monotherapy )Compare. The primary end point was the combined endpoint of cardiovascular death, nonfatal myocardial infarction, and the need for reentry of unstable angina. Median follow-up for 6 years.
RESULTS: In the study, the mean LDL cholesterol level in the simvastatin-ezetimibe group was 53.7 mg / dL (1.4 mmol / L) and the simvastatin monotherapy group was 69.5 mg / dL (1.8 mmol / L ) (P <0.001). The level of LDL decreased significantly in the combination group. The incidence of Kaplan-Meier event was 32.7% in the simvastatin-ezetimibe group at the first 7 years and 34.7% in the simvastatin monotherapy group (absolute risk difference, 2 percentage points; hazard ratio 0.936; P = 0.016). Muscle, gallbladder, liver adverse events and tumor incidence were similar in both groups.
CONCLUSION: Ezetimibe is added to statin therapy, LDL cholesterol levels are further reduced, and cardiovascular outcomes are improved. Moreover, lowering LDL cholesterol levels below the previous target value may provide additional benefit.