Is there an inter-manufacturer difference in generic clopidogrel response?

Abstract

Abstract Background Differences in platelet aggregation response to generic clopidogrel by manufacturer has not been investigated. Purpose Compare rates of clopidogrel response among patients receiving medication produced by two different manufacturers after acute coronary syndrome and/or percutaneous coronary intervention. Methods This quality improvement project included 515 adult patients receiving clopidogrel for acute coronary syndrome or ischemic heart disease and referred for coronary angiography/percutaneous coronary intervention at a large, public hospital. The project was divided into two phases: 1. retrospective collection of baseline data; 2. two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time. The primary outcome was clopidogrel response measured by platelet function testing defined as ADP response <40% on light transmission aggregometry between two manufacturer groups. Aspirin response defined as arachidonic acid response <20% was also measured. Results Of 515 total patients included in both phases (mean [SD] age, 64.5 [11.4] years; 351 [68.2%] men; 450 [87.4%] ACS), 52% were found to be clopidogrel responders based on results of platelet function testing (Table 1 – select variables). Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared to the Manufacturer 2 group (34.8% vs. 55.1%, p=0.03) (Table 2 – select variables). After adjustment for age, sex, BMI, aspirin response, therapeutic hypothermia, LHC indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (OR [95% CI]: 0.96 [0.95–0.97], p<0.001) and manufacturer (OR [95% CI]: 2.45 [1.18–5.22], p=0.02) were associated with clopidogrel response. Conclusions In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability. Funding Acknowledgement Type of funding sources: None.