Pharmacodynamic effects of a new fixed-dose clopidogrel–aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial

Abstract

Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG^®). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, −5 PRU; 90% confidence interval of difference, −23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). “BASE” and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG^® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel–aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.

Keywords:

• Aspirin
• aggregation
• clopidogrel
• platelet

Acknowledgments

The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents.

Declaration of interest

Dr. Jeong has received honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo/Lilly, Haemonetics, Otsuka and Yuhan Pharmaceuticals; and research grants or support from AstraZeneca, Korean Society of Interventional Cardiology, Han-mi Pharmaceuticals, Accumetrics, and Haemonetics. Dr Gurbel reports serving as a consultant fees/receiving honoraria from Daiichi Sankyo, Bayer, AstraZeneca, Merck, Boehringer, New Haven Pharmaceuticals, Janssen, and CSL and receiving grants from the National Institutes of Health, Daiichi Sankyo, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics, New Haven Pharmaceuticals, Duke Clinical Research Institute, Sinnowa, and Coramed. Dr Gurbel has patents in the field of platelet function testing. The other authors report no conflicts of interest.

Funding

This study was partly supported by grants from the Institute of the Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea, and the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2015R1A5A2008833).

Additional information

Funding

This study was partly supported by grants from the Institute of the Hanmi Pharmaceutical Co., Ltd., Seoul, Republic of Korea, and the Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2015R1A5A2008833).