Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis

• Published in: European journal of clinical pharmacology 2021-12, Vol.77 (12), p.1815-1823
• Main Authors: Yang, Mingwen, Ye, Zekang, Mei, Lianlian, Ullah, Inam, Tan, Chuchu, Wang, Guoyu, Gu, Qian, Lu, Yi, Abdus, Samee, Shi, Lu, Gong, Xiaoxuan, Bai, Jianling, Eikelboom, John W., Li, Chunjian
• Format: Article
• Language: English
• Subjects: Aged; Arachidonic acid; Arteriosclerosis; Aspirin; Aspirin - pharmacology; Atherosclerosis; Biomedical and Life Sciences; Biomedicine; Clinical Trial; Coronary Artery Disease - drug therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Isoindoles - pharmacology; Male; Middle Aged; Patients; Pharmacodynamics; Pharmacology/Toxicology; Phenylbutyrates - pharmacology; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - blood; Thromboxane B2 - urine
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-021-03177-y

Purpose This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis. Methods In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PL AA ), and the secondary outcomes included plasma thromboxane B 2 (TXB 2 ) and urinary 11-dehydro-TXB 2 (11-dh-TXB 2 ) levels at the end of each treatment.  Results In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PL AA whereas indobufen group had significantly less suppressed PL AA . Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB 2 . All treatment regimens produced similar inhibition of 11-dh-TXB 2 . In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB 2 at 8 h and 12 h after the last dose. Conclusions Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.