Inhibitory Interaction Between Calcium Channel Blocker and Clopidogrel Efficacy of Cilostazol to Overcome It

• Published in: Circulation Journal Vol. 75; no. 11; pp. 2581 - 2589
• Main Authors: Suh, Jung-Won, Lee, Seung-Pyo, Chae, In-Ho, Bae, Jang-Whan, Park, Kyung Woo, Cho, Myeong-Chan, Kim, Hyo-Soo, Rha, Seung-Woon, Bae, Jang-Ho
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Circulation Society 2011
• Subjects: Aged; Brain Ischemia - etiology; Brain Ischemia - mortality; Calcium channel blocker; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - adverse effects; Cilostazol; Clopidogrel; Death; Drug Antagonism; Drug-Eluting Stents - adverse effects; Female; Humans; Male; Middle Aged; Myocardial Infarction - etiology; Myocardial Infarction - mortality; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet function test; Prospective Studies; Stroke - etiology; Stroke - mortality; Tetrazoles - administration & dosage; Tetrazoles - adverse effects; Thrombosis; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - antagonists & inhibitors
• ISSN: 1346-9843; 1347-4820; 1347-4820
• DOI: 10.1253/circj.CJ-11-0113

Background: The clinical effect of, and additive measures to overcome the possible inhibitory calcium channel blocker (CCB)-clopidogrel interaction in Asian patients undergoing percutaneous coronary intervention is unknown. Methods and Results: A total of 900 Korean patients enrolled for the multicenter, prospective, randomized Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation (CILON-T) trial were divided into 4 groups depending on CCB prescription and type of anti-platelet therapy (dual [DAT] vs. triple [TAT; addition of cilostazol to DAT]) in a 2×2 factorial manner. The primary endpoint was a composite of cardiac death, non-fatal myocardial infarction and ischemic stroke at 6 months after PCI. On-treatment platelet reactivity (OPR) was assessed on VerifyNow P2Y12 assay. Concomitant CCB use increased OPR in the DAT group (mean±SEM: 251.2±7.6 vs. 225.6±5.1; P=0.008), but not in the TAT group (214.5±9.1 vs. 203.4±5.6; P=0.294). Primary endpoint increased by use of CCB in patients with DAT (4.9% vs. 0.9%, P=0.016), but not in those with TAT (0% vs. 1.8%, P=0.346). Addition of cilostazol to DAT reduced OPR and clinical events in patients taking CCB (P=0.007 for P2Y12 reaction units; P=0.027 for thrombotic events). CCB without concomitant cilostazol use was a significant predictor of total thrombotic events. Conclusions: Concomitant use of CCB may weaken the anti-platelet effect of clopidogrel and increase subsequent thrombotic events in Asian subjects. This hazardous CCB-clopidogrel interaction may be overcome by addition of cilostazol. (Circ J 2011; 75: 2581-2589)