Effect of ezetimibe add-on therapy over 52 weeks extension analysis of prospective randomized trial (RESEARCH study) in type 2 diabetes subjects

• Published in: Lipids in health and disease Vol. 16; no. 1; pp. 122 - 9
• Main Authors: Sakamoto, Kentaro, Kawamura, Mitsunobu, Watanabe, Takayuki, Ashidate, Keiko, Kohro, Takahide, Tanaka, Akira, Mori, Yasumichi, Tagami, Motoki, Hirano, Tsutomu, Yamazaki, Tsutomu, Shiba, Teruo
• Format: Journal Article
• Language: English
• Published: London BioMed Central 24.06.2017; BioMed Central Ltd; BMC
• Subjects: Anticholesteremic Agents - therapeutic use; Arteriosclerosis; Atorvastatin; Biomedical and Life Sciences; Cardiovascular disease; Cholesterol; Cholesterol, LDL - blood; Clinical Nutrition; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; Drug therapy; Ezetimibe - therapeutic use; Female; Humans; Hypercholesterolemia; Insulin; Life Sciences; Lipidology; Lipids; Low density lipoprotein; Male; Medical Biochemistry; Mortality; Prospective Studies; Proteins; Research Article; Risk factors; Statins; Type 2 diabetes; Atorvastatin; Pitavastatin; Apo B; Robust Advantage; Ezetimibe
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-017-0508-4

Background Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. Methods In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited. We investigated the difference in cholesterol lowering effect between ezetimibe (10 mg) add-on statin (EAT) group and double-dose statin (DST) group. Changes of parameters related to atherosclerotic event risks were assessed. Results The reduction of LDL-C was larger in the EAT group (28.3%) than in the DST group (9.2%) at 52 weeks as well as the primary endpoint of 12 weeks. EAT achieved significant lower levels of TC and apo B, respectively. Both treatments attained significant reduction in sd-LDL-C or hsCRP on this long-term basis. Notably, sd-LDL-C in EAT reduced as low as 36.1 ± 14.9 mg/dl to reach near the threshold (35.0 mg/dl) for atherosclerosis with significantly higher achievement rate (55.6%) than DST treatment. Simultaneously, hsCRP reduction by EAT attained as low value as 0.52 ± 0.43 mg/l. Conclusions In the present 52-week long-term period, ezetimibe add-on therapy showed a robust advantage in lowering LDL-C and in attaining target LDL-C values compared with the doubling of statin dose. Moreover, it’s meaningful that sd-LDL, powerfully atherogenic lipoprotein, exhibited prominent decrease consistently prominently by ezetimibe add-on therapy. DM patients with hypercholesterolemia are at high risk for CAD, and adding ezetimibe onto usual-dose statin treatment in Japan has been suggested as the first-line therapy for those DM patients who failed to attain the target LDL-C value (UMIN000002593).