Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis


Kesselheim AS, Misono AS, Lee JL, Stedman MR, Brookhart MA, Choudhry NK, Shrank WH. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis [Internet]. Journal of the American Medical Association 2008;300:2514-26.

Date Published:

Dec 3


CONTEXT: Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. OBJECTIVES: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. DATA SOURCES: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. STUDY SELECTION: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. DATA EXTRACTION: We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral. RESULTS: We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. CONCLUSIONS: Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.


Kesselheim, Aaron SMisono, Alexander SLee, Joy LStedman, Margaret RBrookhart, M AlanChoudhry, Niteesh KShrank, William HAG027400/AG/NIA NIH HHS/United StatesK23HL090505-01/HL/NHLBI NIH HHS/United StatesMeta-AnalysisResearch Support, N.I.H., ExtramuralResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.ReviewUnited StatesJAMA : the journal of the American Medical AssociationJAMA. 2008 Dec 3;300(21):2514-26.

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Last updated on 02/02/2016