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Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes: A Cohort StudyComparative Effectiveness of Generic and Brand-Name Statins

Joshua J. Gagne, PharmD, ScD; Niteesh K. Choudhry, MD, PhD; Aaron S. Kesselheim, MD, JD, MPH; Jennifer M. Polinski, ScD, MPH; David Hutchins, MBA, MHSA; Olga S. Matlin, PhD; Troyen A. Brennan, MD; Jerry Avorn, MD; and William H. Shrank, MD, MSHS
[+] Article, Author, and Disclosure Information

From the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and CVS Caremark, Woonsocket, Rhode Island.

Note: Dr. Gagne had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Grant Support: By Teva Pharmaceuticals (2010A057139).

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2942.

Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Gagne (e-mail, jgagne1@partners.org). Data set: Not available.

Requests for Single Reprints: Joshua J. Gagne, PharmD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120; e-mail, jgagne1@partners.org.

Current Author Addresses: Drs. Gagne, Choudhry, Kesselheim, Polinski, and Avorn: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120.

Mr. Hutchins: CVS Caremark, 10001 North 92nd Street, Scottsdale, AZ 85258.

Dr. Matlin: CVS Caremark, 2211 Sanders Road, Northbrook, IL 60062.

Dr. Brennan: CVS Caremark, 1 CVS Drive, Woonsocket, RI 02895.

Dr. Shrank: CVS Caremark, 100 Scenic View Road, Cumberland, RI 02864.

Author Contributions: Conception and design: J.J. Gagne, A.S. Kesselheim, D. Hutchins, T.A. Brennan, W.H. Shrank.

Analysis and interpretation of the data: J.J. Gagne, N.K. Choudhry, J.M. Polinski, D. Hutchins, J. Avorn, W.H. Shrank.

Drafting of the article: J.J. Gagne, D. Hutchins.

Critical revision of the article for important intellectual content: J.J. Gagne, N.K. Choudhry, A.S. Kesselheim, J.M. Polinski, O.S. Matlin, T.A. Brennan, J. Avorn, W.H. Shrank.

Final approval of the article: J.J. Gagne, N.K. Choudhry, A.S. Kesselheim, J.M. Polinski, D. Hutchins, O.S. Matlin, T.A. Brennan, J. Avorn, W.H. Shrank.

Provision of study materials or patients: J.J. Gagne.

Statistical expertise: J.J. Gagne, J.M. Polinski, W.H. Shrank.

Obtaining of funding: J.J. Gagne, W.H. Shrank.

Administrative, technical, or logistic support: J.J. Gagne, D. Hutchins, O.S. Matlin, T.A. Brennan, J. Avorn, W.H. Shrank.

Collection and assembly of data: J.J. Gagne, D. Hutchins.

Ann Intern Med. 2014;161(6):400-407. doi:10.7326/M13-2942
Text Size: A A A

Background: Statins are effective in preventing cardiovascular events, but patients do not fully adhere to them.

Objective: To determine whether patients are more adherent to generic statins versus brand-name statins (lovastatin, pravastatin, or simvastatin) and whether greater adherence improves health outcomes.

Design: Observational, propensity score–matched, new-user cohort study.

Setting: Linked electronic data from medical and pharmacy claims.

Participants: Medicare beneficiaries aged 65 years or older with prescription drug coverage between 2006 and 2008.

Intervention: Initiation of a generic or brand-name statin.

Measurements: Adherence to statin therapy (measured as the proportion of days covered [PDC] up to 1 year) and a composite outcome comprising hospitalization for an acute coronary syndrome or stroke and all-cause mortality. Hazard ratios (HRs) and absolute rate differences were estimated.

Results: A total of 90 111 patients who initiated a statin during the study was identified; 83 731 (93%) initiated a generic drug, and 6380 (7%) initiated a brand-name drug. The mean age of patients was 75.6 years, and most (61%) were female. The average PDC was 77% for patients in the generic group and 71% for those in the brand-name group (P < 0.001). An 8% reduction in the rate of the clinical outcome was observed among patients in the generic group versus those in the brand-name group (HR, 0.92 [95% CI, 0.86 to 0.99]). The absolute difference was −1.53 events per 100 person-years (CI, −2.69 to −0.19 events per 100 person-years).

Limitation: Results may not be generalizable to other populations with different incomes or drug benefit structures.

Conclusion: Compared with those initiating brand-name statins, patients initiating generic statins were more likely to adhere and had a lower rate of a composite clinical outcome.

Primary Funding Source: Teva Pharmaceuticals.


Grahic Jump Location
Figure 1.

Kernel densities for generic and brand-name statin recipients.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Forest plot of secondary and sensitivity analyses.

Grahic Jump Location




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Submit a Comment/Letter
Posted on October 6, 2014
Glen Ross, MD
Sentara Medical Group
Conflict of Interest: None Declared
The article by Gagne et all (1) concluding that patients initiated on generic statin rather than brand-name statin medication had better adherence and more favorable outcomes is provocative. The results suggest that less costly generic statin therapy results in improved health outcomes. Although the study was not designed to determine why compliance was better in the generic statin group, the authors reasonably speculate that cost of therapy could explain the difference.
I would like to propose another possible explanation. Generic and brand-name statin groups were examined for numerous characteristics and found to be similar. Patients were enrolled if they had had no statin prescription in the 180 days prior to current statin drug initiation. However, it does not appear that study participants were screened as to more remote history of prior statin use. Musculoskeletal side effects most commonly prompt patients and their providers to discontinue statin drug use. It might be the case that after such discontinuation, the patient or provider would be more inclined to select a brand-name statin option rather than generic. Patients with adverse reactions to one statin are more likely to react to a second one than a patient new to statin therapy. Thus, it is possible that a disproportionate number of patients in the brand-name statin group discontinued therapy due to side effects, explaining the adherence difference observed. This explanation is not excluded by the study methods and if true, would also call into question the relative perceived advantage of generic vs brand-name statin drug therapy.

Gagne JJ, Choudry NK, Kesselheim AS, Polinski JM, Hutchins D, Matlin OS, et al. Comparative effectiveness of generic and brand name statins on patient outcomes. Ann Intern Med 2014; 161: 400-407. doi: 10.7326/M13-2942
Letter to the editor
Posted on October 14, 2014
Hend Mansoor, Abraham Hartzema
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL
Conflict of Interest: None Declared
We read with interest the study “Comparative effectiveness of generic and brand-name statins on patient outcomes” by Gagne JJ et al published in the Journal. The study used an observational, propensity score–matched cohort design, comparing the effect of the initiation of brand versus generic name statins on medication adherence and cardiovascular events. The design showed several strengths including the use of propensity score-matching, employed subgroup and sensitivity analyses, and use of a negative control outcome (1).

However, some issues need further clarification; the fact that switching between brand and generics was allowed requires cautious interpretation of results. The magnitude of switching was not reported, yet switching is likely with statins given the side effects. Furthermore, the effect of different doses of statins on medication adherence was not examined; higher doses of statins predict poorer adherence and higher tendency to medication switches (2).

The method of prescription pickup was a potential confounder, as patients having their medications mailed to their homes compared to other pickup methods might have a biased proportion of days covered (PDC) estimates. This is particularly important as patients in the generic user group showed higher unemployment rates and lower household incomes, which predisposes residual confounding and lower adherence due to difficulties in medication access (3).

The authors attempted to adjust for “healthy user” effect by controlling for the use of preventive services. However, other factors e.g. health literacy, might contribute to patients’ medication behaviors. In addition, factors associated with non-adherence that are not documented in claims data, but can only obtained through patients’ interviews are vital, therefore, prescribing decisions for the initiation of a generic versus a brand name statin often include patient’s variables (4).

The PDC was assessed once during the study period; however, the change of adherence during the year was unknown. Furthermore, assessment of adherence at 6 months and 1 year would have allowed a more robust assessment of the results, given that medication switches were allowed. Also, the PDC was not reported for other medications, given that most patients were on multiple drugs, which could have been reported as part of the sensitivity analysis.

The use of clinical endpoints was innovative, but the inclusion of a surrogate endpoint e.g. LDL would have strengthen the assumption that patients were adherent to their medications. Finally, one-year of follow up is not sufficient to observe effects for cardiovascular events and mortality due to adherence.

1. Gagne JJ, Choudhry NK, Kesselheim AS, Polinski JM, Hutchins D, Matlin OS, et al. Comparative effectiveness of generic and brand-name statins on patient outcomes: a cohort study. Ann Intern Med 2014;161:400-7.
2. Virani SS, Woodard L, Ramsey D, Ballantyne C, Petersen LA. Is High-Dose Statin Therapy Associated With Lower Statin Adherence Compared With Low-Dose Statin Therapy? An Analysis From A National Cohort. J Am Coll Cardiol; 2014 ;63:A1452.
3. Wallach-Kildemoes H, Andersen M, Diderichsen F, Lange T. Adherence to preventive statin therapy according to socioeconomic position. Eur J Clin Pharmacol 2013;69:1553–63.
4. McGinnis B, Olson KL, Magid D, Bayliss E, Korner EJ, Brand DW, Steiner JF. Factors related to adherence to statin therapy. Ann Pharmacother 2007;41:1805–11.

Submit a Comment/Letter

Summary for Patients

Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes

The full report is titled “Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes. A Cohort Study.” It is in the 16 September 2014 issue of Annals of Internal Medicine (volume 161, pages 400-407). The authors are J.J. Gagne, N.K. Choudhry, A.S. Kesselheim, J.M. Polinski, D. Hutchins, O.S. Matlin, T.A. Brennan, J. Avorn, and W.H. Shrank.


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