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Did Generic Clopidogrel Commercialization Affect Trends of ER Consultations and Hospitalizations in the Population Treated with Clopidogrel?

Abstract

Background

Clopidogrel has been widely used to prevent atherothrombotic events. Since 2011, pharmacists have offered their patients the opportunity to switch to generic clopidogrel, an economic alternative. Whether bioequivalence of generic cardiovascular drugs translates into clinical equivalence at a population level remains unclear and needs to be further documented.

Objective

We aimed to evaluate the impact of generic clopidogrel commercialization on adverse events (AEs): hospitalizations or emergency room (ER) consultations.

Methods

This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. We included all patients ≥ 66 years old who were users of the brand-name clopidogrel or a generic version (n = 6) 24 months before and up to 12 months after generics commercialization. Rates of AEs were computed, and periods before and after generics commercialization were analyzed by segmented regression models along with exploratory analyses (generic vs. brand name). Sensitivity analyses were also performed using stratification of the time series by (1) sex, (2) the number of prevalent cardiovascular comorbidities, and (3) socioeconomic status.

Results

Time series were constituted of 89,525 clopidogrel users (mean age 78 years, 45% women, 71% ischemic heart disease, 34% stroke). For all users, there was a mean rate of 157 AEs per 1000 user-months, stable trend before (−0.1% [95% confidence interval −0.3 to 0.1] and after (0.0% [− 0.5 to 0.6]) generics commercialization. In exploratory analyses, once generic clopidogrel versions were commercialized, rates of AEs were 19.2% (95% CI 11.7–26.7) higher for generic versus brand-name users. This difference persisted up to 1 year. Sensitivity analyses yielded similar results.

Conclusions

The population treated with clopidogrel had similar rates of hospitalizations or ER consultations before and after generics commercialization. However, differences in rates of hospitalizations or ER consultations between generic and brand-name clopidogrel users may represent a drug safety signal which remains to be validated. Using a different study design, permitting adjustment for potential confounders, could be useful in this regard.

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Acknowledgements

This study was conducted at the National Public Health Institute of Quebec (INSPQ) as part of the continuous chronic disease surveillance mandate granted by the provincial minister of health and social services. Jacinthe Leclerc is the recipient of a studentship from the program Ministère de l’Éducation et de l’Enseignement supérieur-Universités. Dr. Paul Poirier is a senior clinical researcher of the Fonds de recherche du Québec-Santé (FRQ-S). Dr. Line Guénette holds a Junior-1 clinical researcher salary award from the FRQ-S in partnership with the Société québécoise d’hypertension artérielle (SQHA).

Author information

Correspondence to Paul Poirier.

Ethics declarations

Funding

There was no funding for this study, part of the continuous chronic disease surveillance mandate in the province of Quebec, Canada.

Conflict of interest

Paul Poirier has received honoraria for continuing medical education/consultant/expert events from Abbott Vascular, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, NovoNordisk, Pfizer, Roche, Sanofi-Aventis, Servier and Valeant. The industry had no influence in any decisions made through this project. Jacinthe Leclerc, Claudia Blais, Louis Rochette, Denis Hamel and Line Guénette have no conflict of interest relevant to the content of this article.

Contributions of Authors

Protocol design: Jacinthe Leclerc, Paul Poirier, Claudia Blais, Line Guénette, Denis Hamel and Louis Rochette. Data acquisition, analysis: Louis Rochette, Denis Hamel and Jacinthe Leclerc. Interpretation of data: Jacinthe Leclerc, Paul Poirier, Claudia Blais, Line Guénette, Denis Hamel and Louis Rochette. Drafting of the work: Jacinthe Leclerc. Revisions of critically important intellectual content: Claudia Blais, Line Guénette, Denis Hamel, Louis Rochette and Paul Poirier. Final approval of the version to be published: Paul Poirier. Agreement to be accountable for all aspects of the work: Jacinthe Leclerc, Claudia Blais, Louis Rochette, Denis Hamel, Line Guénette and Paul Poirier.

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Leclerc, J., Blais, C., Rochette, L. et al. Did Generic Clopidogrel Commercialization Affect Trends of ER Consultations and Hospitalizations in the Population Treated with Clopidogrel?. Drugs Aging 36, 759–768 (2019). https://doi.org/10.1007/s40266-019-00679-4

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