Physicians' Academy for Cardiovascular Education

Generic ARBs associated with more adverse events compared with branded ARBs

Impact of the Commercialization of Three Generic Angiotensin II Receptor Blockers on Adverse Events in Quebec, Canada - A Population-Based Time Series Analysis

Leclerc J, Blais C, Rochette L, et al. - Circ Cardiovasc Qual Outcomes 2017;10:e003891

Background

Generic and brand-name drugs are assumed to be clinically equivalent and are used interchangeably once approved by health authorities. Most of population-based, time series analyses support generics commercialization, but they are only evaluating prescription rates or economical outcomes [1-3]. Whether bioequivalence of generic drugs translates into clinical equivalence at a population level is unclear.

In this study, the entry of the generic ARB analogs in the Canadian market was characterized, and the impact of generic ARBs commercialization on adverse events was evaluated, in elderly patients in real-life conditions.

The data of this observational retrospective interrupted time series study was retrieved from the Quebec Integrated Chronic Disease Surveillance System (QICDSS) [4]. The 3 brand-name ARBs losartan, valsartan, and candesartan, as well as 16 generic analogs were studied in all dosages. The interrupted time series were constituted of all patients (N=136 177), aged ≥66 years old, who were observed every month for adverse events, namely ER consultations and hospitalizations, 24 months before and 12 months after generics commercialization.

Main results

Conclusion

The use of generic ARBs resulted in higher rates of hospitalizations and emergency room consultations compared with branded ARBs. The difference was most pronounced in the first month and with candesartan. These findings suggest that there is a need for more accurate pharmacovigilance reporting of generic and brand-name drugs in real-life conditions.

Editorial comment

In his editorial article, Alter sets the scene first with the following observation: ‘Although manufacturers must prove that generic analogues are bioequivalent to their brand-name comparators, the validity of generic drug substitution policies and their investment returns rest on the assumption that such drugs are clinically interchangeable. The extent to which such assumptions have been tested and proven remains unclear.’

Subsequently he discusses the limitations of the study published by Leclerc et al, including:

  • the study design, which did not incorporate risk-adjustment methodology
  • the reasons for the increased emergency room visits and hospitalizations linked to generic drugs, which were not investigated
  • the adverse events associated with generic drugs, which may have occurred with the branded drugs as well
  • a selection bias, which is possible for those who received generic drugs

The author concludes: ‘If we are to continue to promote drug surveillance research, we may be leaving ourselves vulnerable to having to address clinical uncertainty when faced with imperfect evidence. Solutions will almost certainly necessitate much broader and more comprehensive collaboration between clinical guideline developers, regulatory bodies, policy makers, and the scientific community—perhaps even a conceptual framework to help us map out our next steps, our priorities, and our action plans may be useful. The investment in time, effort, and resources may not be small but may yield a return on investment that approaches or surpasses those associated with generic drugs themselves.’

References

Show references

Find this article online at Circ Cardiovasc Qual Outcomes