Influence of rabeprazole and famotidine on pharmacodynamic profile of dual antiplatelet therapy in clopidogrel-sensitive patients: The randomized, prospective, PROTECT trial

Abstract

Although acid suppressants are needed to attenuate gastrointestinal bleeding (GIB) after percutaneous coronary intervention (PCI), pharmacodynamic interaction between clopidogrel and proton pump inhibitor (PPI) can increase the risk of high platelet reactivity (HPR). We sought to evaluate serial changes of platelet measures and influence of rabeprazole on platelet measures. After 600-mg clopidogrel loading for elective PCI, clopidogrel-sensitive patients were recruited and randomly assigned to add rabeprazole of daily 20 mg (n = 40) or famotidine of daily 40 mg (n = 40). Platelet measures were performed with light transmittance aggregometry and VASP-P assay. Primary endpoint was 5 μM ADP-induced platelet aggregation (PA) at 30-day follow-up. HPR was defined as 5 μM ADP-induced PA > 46%. Baseline platelet measures did not differ significantly between the groups. The 30-day level of 5 μM ADP-induced PA was similar between the famotidine vs. rabeprazole group (30.0 ± 16.4% vs. 30.2 ± 13.9%, P= .956). In addition, other platelet measures were comparable between the groups. At 30-day follow-up, the incidence of HPR was similar between the famotidine and rabeprazole groups (20.5% vs. 15.4%; P= .555). In conclusion, adjunctive use of rabeprazole showed the similar antiplatelet effect even in clopidogrel-sensitive patients compared with adjunctive famotidine, which may support the similar effect of rabeprazole and famotidine on the antiplatelet effect of dual antiplatelet therapy with clopidogrel plus aspirin.

Keywords:

• Clopidogrel
• famoditine
• GI bleeding
• rabeprazole

Conflicts of interest

Dr. Jeong has received honoraria for lectures from AstraZeneca, Sanofi-Aventis, Daiichi Sankyo/Lilly, Haemonetics, Otsuka, Han-mi Pharmaceuticals and Yuhan Pharmaceuticals; and research grants or support from AstraZeneca, Korean Society of Interventional Cardiology, Han-mi Pharmaceuticals, Daewoong Pharmaceuticals, Chong Kun Dang Pharmaceuticals, and Haemonetics. The other authors report no conflicts of interest.

Additional information

Funding

This study was partly supported by research grants from the Chong Kun Dang Pharm., 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). 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.