Jacinthe Leclerc1,2,3, Claudia Blais1,4, Louis Rochette1, Denis Hamel1, Line Guénette4,5, Paul Poirier6. 1. Institut national de santé publique du Québec, Quebec City, Canada. 2. Nursing Department, Université du Québec à Trois-Rivières, Trois-Rivières, Canada. 3. Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Canada. 4. Faculty of Pharmacy, Université Laval, Quebec City, QC, Canada. 5. Centre de recherche du CHU de Québec-Université Laval, Axe Santé des populations et pratiques optimales en santé, Quebec City, Canada. 6. Faculty of Pharmacy, Université Laval, Quebec City, QC, Canada. paul.poirier@criucpq.ulaval.ca.
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.
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.
Authors: A Komosa; J M Siller-Matula; J Kowal; M Lesiak; A Siniawski; M Mączyński; M Michalak; T Mularek-Kubzdela; S Grajek Journal: Platelets Date: 2014-02-05 Impact factor: 3.862
Authors: Cynthia A Jackevicius; Jack V Tu; Harlan M Krumholz; Peter C Austin; Joseph S Ross; Therese A Stukel; Maria Koh; Alice Chong; Dennis T Ko Journal: J Am Heart Assoc Date: 2016-04-19 Impact factor: 5.501