Toward Personalized DAPT: Is There an Inter-Manufacturer Difference in Generic Clopidogrel Response?

J Invasive Cardiol. 2022 Dec;34(12):E873-E878. doi: 10.25270/jic/22.00268. Epub 2022 Nov 23.

Abstract

Objective: To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention.

Methods: This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry.

Results: Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. 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 with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.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.

Keywords: antiplatelet therapy; clopidogrel; coronary artery disease; generics; platelet function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin*
  • Clopidogrel / therapeutic use
  • Humans
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies

Substances

  • Aspirin
  • Clopidogrel