The American Journal of Managed Care July 2009
Lipid Profile Changes Associated With Changing Available Formulary Statins: Removing Higher Potency Agents
With the exception of high-density lipoprotein cholesterol, fasting lipid profiles were not significantly changed after higher potency statins were removed from prescription formularies.
In this study, patients taking atorvastatin were changed to an alternate statin because of formulary restrictions. As a result, patients’ total cholesterol, LDL, and triglyceride levels remained unchanged and HDL levels slightly increased, despite only 34% of conversions being considered therapeutically equivalent. Most data published regarding statin conversion evaluate changing to a uniform (usually more potent) statin, resulting in an improved lipid profile.12-16 The data presented here suggest that the formulary change from a higher potency statin (atorvastatin) to a moderate potency statin (simvastatin, pravastatin, or lovastatin) does not affect the lipid profile as one may expect. Taken in conjunction with the 2004 update to the National Cholesterol Education Program Adult Treatment Panel III, these data should suggest to providers that moderate doses of generically available statins are just as effective as higher doses of brand-only statins for controlling lipid panels. Additionally, our data are unique in that they challenge previously published data that indicated usual care for formulary statin changes results in significantly worse LDL.17
High-density lipoprotein levels significantly increased for patients after switching statins (42.5 mg/dL to 44.4 mg/dL; P = .018). Clinically, this increase carries with it the potential for a decrease in myocardial infarction or death from coronary heart disease, as a 1-mg/dL increase in HDL has been linked to a 4.5% decrease in these outcomes.18 This increase in HDL levels observed in the research results reported previously was expected. Previous research on the lipid-lowering potential of various statins suggests that as doses of atorvastatin approach 80 mg daily, the medication tends to decrease HDL rather than have a slightly positive or neutral effect.11 The increase in HDL in this patient population does not translate into a decreased risk of myocardial infarction or death from coronary heart disease, as this research was only designed to look at surrogate markers and did not assess clinical end points.
Low-density lipoprotein levels were expected to worsen, given the potential for suboptimal and delayed conversions. However, even with a 34% appropriate change rate, most aspects of the lipid panel remained unaffected. What was most concerning was the mean time to make the change from atorvastatin to an alternate statin (2.9 months). Although pharmacy records were not evaluated to determine whether the patient was treated during this time, we were cognizant that there was not a grace period for coverage and patients had little to no access to other sources for replacement prescriptions. Therefore, we were forced to work from the idea that patients went without medication. It is not known whether this lapse in therapy was harmful to patient outcomes, but some research shows that even brief discontinuation of statins may result in rapid elevations in surrogate markers related to myocardial infarction, including C-reactive protein and LDL.23 Though this research shows that lipid profiles remained unchanged, the follow-up profiles were performed at least 6 weeks after initiating the alternate statin. Fasting lipid panel information was not available for the period of time between stopping atorvastatin and starting an alternate agent, so we cannot conclude how this delay affected this patient population’s lipid profile during that time.
There are several challenges in interpreting these data, including patient adherence to statin therapy, the suggested slightly incremental improvements in lipid profiles when increasing statin strength or formulation, and the use of anticipated lipid-lowering effects as a marker for appropriate therapeutic interchange. These potential biases may explain how LDL concentrations in patients switched from atorvastatin 40 mg and 80 mg improved after providers changed agents.
First, the evidence surrounding patient adherence to statin therapy states that as many as 50% of patients will discontinue therapy within 6 months of the initial dose.8,24 Given that we did not assess adherence to atorvastatin before its discontinuation, there is the possibility that patients were not taking their medication at the time of the lipid panel most immediately before changing therapies. The follow-up lipid panel often was performed within 6 months of changing therapy, so patients were more likely to be adherent to lipid-lowering therapy. Therefore, our postchange observation could show a lower LDL concentration, despite patients being on a less potent statin.
Second is the discussion about whether incremental increases or decreases in statin dose have significant lipidreducing potential. On average, the LDL-lowering potential when incrementally increasing or decreasing a statin dose is approximately 6%.11 This relatively small difference may not have been sufficient enough to show a significant change in lipid profiles, especially given the size of the population in this study. However, even with 66% of the dose change considered inferior conversions, the follow-up lipid profiles
slightly trended toward improvement.
This research suggests that when this specific pharmacy benefit manager changed the formulary availability of a statin, control of a patient’s lipid profile was not significantly affected. This research is based on individual effectiveness and not average patient outcomes. Patients switched from a highpotency statin to a moderate-potency statin, even though the majority of switches resulted in potency reductions, did not have worsening lipid panels.
The implications for managed care and third-party payers as a result of this study are favorable for decreasing medication costs without jeopardizing patient health. Formulary restrictions and the use of generic drugs can save $8 billion to $10 billion per year at retail pharmacies.25 As the cost of prescription drugs continue to rise, generic substitutions that are identical or bioequivalent can prove useful to many thirdparty payers and managed care plans in providing a comprehensive prescription benefit without decreasing quality of patient outcomes.
Of greatest concern in this research is the almost 3-month delay in making the necessary medication regimen substitutions. Larger scale, controlled research that looks more closely at long-term morbidity and mortality outcomes within managed care plans or third-party payers with formulary restrictions will better identify any risks that may be associated with changing statin formulary availability. Until then, efforts should be focused on strategies to decrease the time it takes to make the necessary substitutions to formulary alternatives.
Author Affiliations: From the Department of Pharmacy Practice (DSL, CMS) and the Department of Pharmaceutical Sciences (MRT), Wilkes University, Wilkes Barre, PA.
Funding Source: None reported.
Author Disclosure: The authors (DSL, CMS, MRT) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (DSL, MRT); acquisition of data (DSL, CMS); analysis and interpretation of data (DSL, CMS); drafting of the manuscript (DSL, MRT); critical revision of the manuscript for important intellectual content (DSL, CMS, MRT); provision of study materials or patients (DSL); and administrative, technical, or logistic support (MRT).
Address correspondence to: Daniel S. Longyhore, PharmD, Department of Pharmacy Practice, Wilkes University, 84 W South St, Wilkes Barre, PA 18766. E-mail: firstname.lastname@example.org.
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