As current opinion that bioequivalent generics may not be clinically equivalent, may or may not be unfounded, efforts have been made to assemble all empirical tests on the equivalence of cardiovascular drugs in terms of their clinical effect.

Research

An excellent start has been made by the team of Kesselheim et al. in the Division of Pharmacoepidemiology and Pharmacoeconomics at the Brigham and Women's Hospital in Boston, USA. This team performed a systematic search of the peer-reviewed literature, between 1984 and 2008, for studies relating to cardiovascular medicine and comparing clinical endpoints with at least one brand-name drug with their generic counterpart. They also evaluated the content of editorials in the literature to determine the concurrent opinion on generic substitution.

What they found was that, even though the empirical evidence gathered thus far does not support the idea that brand-name drugs used in cardiovascular disease are better, in terms of safety or efficacy, than their generic counterparts, a substantial number of editorials in the peer-reviewed literature counsel against the interchangeability of these drugs.

Of the initial 8,556 records identified initially, 47 articles fit their criteria for more detailed analysis and these covered nine different subclasses of cardiovascular drugs. Almost half of the included studies were primarily bioequivalence studies with pharmacokinetic comparisons and more than a third involved only young, healthy subjects.

The 47 studies covered nine different subclasses of cardiovascular drugs, including Narrow Therapeutic Index (NTI) drugs. The clinical outcomes included vital signs, such as clinical laboratory values, adverse effects and other morbidity and healthcare system utilisation, including clinic and emergency department visits.

Forty-three editorials and commentaries were identified; of these, 53% expressed a negative view of the interchangeability of generic drugs compared with 28% that encouraged generic substitution, the remaining articles not reaching a conclusion either way. Thus, more than half of the opinion pieces expressed a negative view of generics, even though there is little evidence to support this. One possible explanation for this discrepancy could be that the opinion pieces are more likely to focus on the personal concerns of the physicians based on their own anecdotal experience. Another possibility raised by Kesselheim et al. is that the conclusions may have been more biased in favour of the brand-name pharmaceutical manufacturers due to financial relationships, which, in almost half of the cases of the opinion pieces did not fully disclose their source of funding.

Despite the several limitations inherent in this systematic literature search and meta-analysis (including one objection published later that the study was over-simplified in the sense that the authors did not consider the case report materials in some editorials and articles), the results indicate that it is reasonable for physicians and patients to base their opinions on whether a generic treatment can be substituted instead of a brand-name drug on the FDA's bioequivalence rating and that these ratings can be used as a proxy for clinical equivalence among a number of important cardiovascular drugs, even in the more high-risk category of NTI drugs, such as with warfarin.

Conclusion

To limit the distrust of generic substitution, which appears to be unfounded, the popular media and peer-reviewed literature could choose to have a more strict editorial policy towards publishing opinion pieces based solely on anecdotal evidence. These avenues of dissemination could alleviate the present situation of affairs and reduce barriers to appropriate generic drug use and the unnecessary augmentation in expenditure without leading to an improvement in clinical outcomes and quality of life for the patient.

Related articles

The therapeutic equivalence of brand-name and generic narrow therapeutic index (NTI) cardiovascular drugs

The therapeutic equivalence of antiplatelet agents, ACE-inhibitors, statins and alpha-blockers

The clinical equivalence of generic and brand-name calcium channel blockers

The clinical equivalence of brand-name beta-blockers and their generic counterparts

Are generic diuretics clinically equivalent to their brand-name counterparts for the management of cardiovascular disease?

The rise in power of generic drugs

References

1. Kesselheim AS, Misono AS, Lee JL, Stedman MR, Brookhart MA, Choudry NK, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008;300(21):2514-26.

2. Reiffel JA. Equivalence of generic and brand-name drugs for cardiovascular disease. JAMA. 2009;301(16):1655.