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.
Objective: To review the fasting lipid panel changes that occurred after removing higher potency statins from a prescription formulary.
Study Design: Retrospective chart review.
Methods: Researchers compiled data for patients in a medical clinic receiving pharmacy benefits from a particular managed care plan. Patients enrolled in the benefits program at least between June 2006 and June 2007 were evaluated for atorvastatin use before January 1, 2007. After January 1, patients on atorvastatin were prescribed new statins according to the program’s preferred drug list. Patients treated with atorvastatin were reviewed for fasting lipid panel results while on atorvastatin; these results then were compared with fasting lipid panels after the formulary change took place. Total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride values were examined for changes. Appropriateness of the replacement statin also was evaluated using statin equivalency charts.
Results: Values for total cholesterol, low-density lipoprotein, and triglycerides were not significantly different from baseline to follow-up. High-density lipoprotein values did significantly increase over the study period. Only 34% of statin prescriptions were considered appropriately converted to equipotent or higher potency doses. The mean time to documentation of statin conversion was 2.9 months.
Conclusions: Removing higher potency statins from the formulary did not significantly change a population’s fasting lipid panel except for a significant increase in high-density lipoprotein. Although multiple factors may have contributed to this effect, the results of this investigation suggest that changing formulary statins will not alter the surrogate lipoprotein markers associated with poor cardiovascular outcomes.
(Am J Manag Care. 2009;15(7):409-414)
The higher potency agents (atorvastatin and rosuvastatin) are available only under their proprietary names, whereas the moderate potency statins (simvastatin, lovastatin, and pravastatin) are more readily available through multiple generic manufacturers.
- Removing higher potency statins from the formulary did not significantly influence a population’s fasting lipid panel except for a significant increase in high-density lipoprotein.
- This lack of difference was seen with only 34% of statin prescriptions considered appropriately converted to equipotent or higher potency doses.
In 2007, approximately 13 million persons were treated with atorvastatin, accounting for $6.16 billion in sales. Although the dollar amount has remained relatively unchanged over the last 5 years, third-party payers and managed care plans continue to look for ways to decrease cost.4,5 This is commonly done by selecting several preferred cheaper generic substitutions and/or brand name options that are then included on the company’s prescription drug formulary. A managed care plan’s formulary selection affects many aspects of care, including the provider’s choice of medication and the patient’s satisfaction with therapy, as well as the patient’s adherence to lipid-lowering therapy.6,7 The development of a medication formulary gives these third-party payers a cost-effective way to provide quality care. When a generic and/or preferred option is chosen, both patients and payers benefit. Adhering to a formulary will decrease cost to payers, resulting in discounted pricing for the patient.7 Also, research has shown that when patients are prescribed medications included on their prescription insurance formulary, their likelihood of remaining adherent to the medication regimen is increased.8
Although patients may remain adherent to the medication regimen, these drugs are selected on the basis of average patient outcome, not individual effectiveness.2 It is important that managed care plans be careful to not compromise individual patient health when decreasing the cost of prescription drugs. In the case of prescription formularies, limiting access to higher potency statins may affect a patient’s and a provider’s ability to reach therapeutic fasting lipid panel levels in a reasonable and safe amount of time.9 In addition, very strict limitations could hinder patients’ access to the medication during a critical point in their therapy such as immediately post–myocardial infarction.10
Although most statins may be considered equivalent with regard to primary and secondary prevention of cardiovascular disease, the lipid-lowering potential of each individual statin is based on the agent’s potency and dose.11 These differences can potentially affect patients’ ability to reach their fasting lipid panel goals. Since December 2001, 3 of the 6 available statins have been approved in generic formulations, thereby offering a less expensive option for third-party payers and managed care plans.
Multiple clinical trials have demonstrated that changing to a more potent statin is associated with additional low-density lipoprotein (LDL) reduction.12-16 However, because most of the higher potency statins still are available only under their brand name, their managed care availability may be limited.
When a provider is prompted to change from a nonformulary medication to a formulary medication, the opportunity arises to evaluate the patient’s current lipid levels and reassess the appropriateness of statin choice and dose. Miller et al recently found that the “usual care” associated with switching from atorvastatin during a formulary change resulted in a significant increase in LDL, non–high-density lipoprotein (HDL), and total cholesterol.17 These results imply that the practice of therapeutic statin conversion during a formulary change may need more guidance. Although prescribers may be aware of the potency differences between the available statins, we cannot conclude that they are aware of the necessary dose changes when changing to a different statin. An inappropriate, suboptimal dose change could result in a worsened
lipid profile and increased risk for cardiovascular event.
Our objective was to investigate the changes in fasting lipid panels based on individual effectiveness in a population that underwent a similar formulary change and needed statin conversion.
This retrospective chart review was conducted with St. Luke’s Hospital and Health Network in Bethlehem, Pennsylvania, in an internal medicine primary care clinic. Each patient evaluated underwent a statin conversion after a managed care plan and prescription insurance provider removed atorvastatin from the preferred drug formulary. All information was gathered to ensure patient privacy and the protocol was reviewed and approved (deemed exempt) by the institutional review board of the St. Luke’s Hospital and Health Network.
Patients were identified using a member census provided monthly by the managed care plan. Patients were included if they were age 18 years or older and were enrolled in the managed care plan from at least June 2006 to June 2007. Patients who had been enrolled before June 2006 and/or continued beyond June 2007 also were eligible. Finally, patients had to have started taking atorvastatin (Lipitor, Parke-Davis & Pfizer Inc, New York, NY) at any dose prior to June 2006. Patients taking atorvastatin after the formulary change date because of prior authorization approval were included in the analysis.
Patients were excluded if they were not taking atorvastatin prior to June 2006, did not have a baseline lipid panel documented at least 6 weeks after starting the last documented atorvastatin dose, or did not have a follow-up lipid panel documented at least 6 weeks after starting the latest replacement statin dose. Patients also were excluded if they had baseline or follow-up triglycerides greater than 400 mg/dL without a direct LDL value, or if their atorvastatin dose or replacement statin dose was not documented in the medical chart. Patients were not excluded if they were using concurrent nonstatin lipid-lowering agents such as nicotinic acid, fibrates, bile acid
sequestrants, or absorption inhibitors.
The primary end point was the observed change in fasting lipid panel components after converting from atorvastatin to another formulary statin. Follow-up assessments used the first fasting lipid panel at least 3 months after the medication change was prescribed. The population also was subdivided and compared as “high risk” patients, requiring LDL cholesterol to be less than 100 mg/dL, and moderate- to low-risk patients, requiring LDL cholesterol to be less than 130 mgdL. As a secondary end point, we evaluated the same criteria used in the primary end point for each baseline atorvastatin dose. In addition, we reviewed the data for appropriateness of the replacement statin based on LDL-lowering potential (Table 1).
For this research, appropriateness was defined as being at least equipotent to the last documented atorvastatin dose with regard to LDL-lowering potential. Given that we did not interview or assess the patient for adherence, appropriateness did not include evaluating whether a dose adjustment was needed based on the baseline fasting lipid panel. If the patient was continued on atorvastatin at the same or greater dose with prior authorization approval, this treatment was considered appropriate. We also evaluated the time elapsed from the date of the formulary change (January 1, 2007) to documented statin change in the patient’s medical record. During this time, patients were assumed to be without statin therapy as the pharmacy benefits manager did not offer a formulary change grace period. Changes made during January 2007 were valued as zero months.
All data collection and statistical analyses were performed using Microsoft’s Access and Excel (Access 2004 and Excel 2004 for Macintosh; Microsoft Corp, Redmond, WA). The differences in fasting lipid profiles (total cholesterol, LDL, HDL, and triglycerides) from baseline with atorvastatin treatment to follow-up with a replacement statin were evaluated using the t test. Appropriateness and mean time to statin change were not evaluated for statistical significance and are reported as descriptive statistics only. All t tests were performed using a 2-sided alpha of .05 unless otherwise noted.
Using the managed care program enrollment time frame described in the Methods section, 328 patients were evaluated for inclusion in the study. Of these, 102 patients were actively receiving atorvastatin for primary and secondary prevention of coronary artery disease. Thirty-one patients were excluded from this group for various reasons including triglycerides greater than 400 mg/dL without a direct LDL value, no baseline lipid panel, no follow-up fasting lipid panel, or atorvastatin change not noted in the medical record.
A more detailed description is provided in Table 2. Demographics for patients included in the evaluation are reported in Table 3.
After comparing fasting lipid profiles for the primary end point, only HDL levels changed significantly. Average baseline HDL levels were measured as 42.5 mg/dL on atorvastatin compared with 44.4 mg/dL after starting the alternate statin (P = .018). Though slightly improved, changes were not significant for LDL (104.0 mg/dL vs 98.9 mg/dL; P = .417) or triglycerides (145.8 mg/dL vs 142.5 mg/dL; P = .637). Total cholesterol was slightly increased (171.6 mg/dL vs 172.3 mg/dL; P = .885).
In the high-risk subgroup (n = 39), 64.1% of patients had an LDL of less than 100 mg/dL while taking atorvastatin at any dose. After the formulary change and statin conversion, 71.8% of patients had an LDL of less than 100 mg/dL. In the moderate- to low-risk subgroup (n = 32), 87.5% of patients had an LDL of less than 130 mg/dL on atorvastatin, which decreased to 81.3% after the formulary change and conversion. Though neither comparison resulted in a statistically significant difference, the small subgroup size did not allow for appropriate power.
For the secondary end point, we chose to evaluate whether changes in lipid panel parameters were significant with respect to specific atorvastatin doses (Table 4). Statistically significant changes were noted only for total cholesterol in patients originally treated with atorvastatin 20 mg (n = 10; 158.9 mg/dL vs 181.9 mg/dL; P = .019) and for triglycerides in patients originally treated with atorvastatin 80 mg (n = 15; 180.5 mg/dL vs 150.1 mg/dL; P = .049). The change in HDL for patients treated with atorvastatin 20 mg trended toward significant (40.0 mg/dL vs 43.8 mg/dL; P = .054), but did not reach statistical significance.