Abstract: Impact of the Commercialization of Three Generic Angiotensin II Receptor Blockers on Adverse Events in Quebec, Canada

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)