Therapeutic Dose Assessment of Patient Switching from Atorvastatin to Simvastatin

June 1, 2007

Objective:

Objective: Patient switching of prescription drug brands within a therapeutic class has become more prevalent with tiered drug plan formularies. Although switching from more expensive brand name drugs to generic equivalents may reduce aggregate prescription costs, therapeutic benefit may be compromised if the patient is not switched to a drug with an equivalent therapeutic profile. This study examined whether patients switching from branded atorvastatin to either a branded or generic simvastatin were prescribed a therapeutically equivalent or higher dose, as opposed to a lower therapeutic dose.

Methods: Study patients were selected from a national longitudinal database of 1.4 billion annual prescription drug claims. All patients active in the database during the study period (9/01/2005 to 9/30/2006) with a prescription drug claim for atorvastatin in the index month (9/2005) were selected. The 453 409 patients in the study period were followed for 12 months to determine the percent switching to simvastatin and their relative therapeutic doses after switching. Patients switching to the same or lower milligram dose of simvastatin were classified as receiving a lower therapeutic dose compared with their atorvastatin dosing.

Results: Among patients using atorvastatin at the beginning of the study, 13 530 (3%) switched to simvastatin by the end of the study period. Medication changes resulted in a lower therapeutic dose in 38% of the switches. The percent of switches resulting in a lower therapeutic dose were 18% for those switching from 10 mg, 43% for those switching from 20 mg, 73% for those switching from 40 mg, and 100% for those switching from 80 mg.

Conclusions: A significant proportion of patients switching from atorvastatin to simvastatin received a lower therapeutic dose, which may have an adverse impact on patients' quality of care and health status. Further research is needed to assess the potential negative effect on patient outcomes.(Am J Manag Care. 2007;13:S80-S85)Patient switching of prescription drug brands within a therapeutic class has become increasingly prevalent with tiered drug plan formularies. Although switching from more expensive brand name drugs to less expensive brands or generic equivalents may reduce aggregate prescription costs, therapeutic benefit may be compromised if the patient is not switched to a drug with an equivalent therapeutic profile. This could have especially important implications for the treatment of asymptomatic conditions, in which the loss of benefit might not be immediately obvious–for example, cardiovascular risk reduction.

Coronary heart disease (CHD) affects an estimated 13.2 million persons in the United States, and is the single largest cause of death among both men and women, accounting for 1 of 5 US deaths in 2003.1 Low-density lipoprotein cholesterol (LDL-C) is an important risk factor for CHD; randomized controlled trials have demonstrated that lowering LDL-C reduces the risk for major coronary events. The National Cholesterol Education Program Adult Treatment Panel III guidelines, published in 2002, identified LDL-C as the primary target of lipid-lowering therapy.2,3

Statins are among the most commonly prescribed and potent LDL-C—lowering agents; however, they differ in their therapeutic profiles. For example, although the recommended dosage ranges for simvastatin and atorvastatin are similar (5-80 mg/day and 10-80 mg/day, respectively4,5), the 2 drugs differ in potency, as discussed below.

A number of randomized studies have compared the effects on LDL-C of atorvastatin versus simvastatin at various dose levels.6-19 These studies differ in design (open-label or double-blind; parallel-group or crossover), numbers of patients randomized to atorvastatin versus simvastatin (range, <100 to >1700), treatment duration (range, 6-54 weeks), patient characteristics (mean baseline LDL-C levels ranging from approximately 172.5-346 mg/dL), and dosing regimens (fixed-dose, dose escalation, or titration to target). Despite these differences, it has been a consistent finding that atorvastatin is significantly more potent than simvastatin at milligram-equivalent doses–including 10 mg,6-8,10,11,14,16 20 mg,7,17,19 40 mg,7,19 and 80 mg.13,15,18

A review20 of 5 of the above studies7,9,12,13,16 found that both drugs reduce LDL-C in a dose-dependent manner, and that the percent decrease of LDL-C from baseline is slightly greater with atorvastatin 10, 20, or 40 mg than with simvastatin 20, 40, or 80 mg, respectively. Similar findings were reported in a post-hoc analysis21 of 3 studies.9,12,13

We examined whether patients switching from atorvastatin to either branded or generic simvastatin received therapeutically equivalent (or higher) simvastatin doses. For purposes of this study, simvastatin doses of 20, 40, and 80 mg were considered therapeutically equivalent to atorvastatin doses of 10, 20, and 40 mg. Because the maximum recommended dosage of simvastatin is 80 mg/day, there is no simvastatin dose equivalent to atorvastatin 80 mg.

Methods

We conducted a retrospective, patient-level analysis of pharmacy claims for patients with an atorvastatin prescription dispensed in September 2005, the index month.

The claims were obtained from Surveillance Data Inc's data warehouse (Table 1) in National Council for Prescription Drug Programs 5.2 format. The claims are collected electronically on a daily basis from approximately 40 000 retail pharmacies covering all 50 states. The volume of claims exceeds 1.4 billion annually dispensed prescriptions. Each patient in the database is assigned a unique synthetic identification number allowing for the longitudinal tracking of the claims per patient over time.

All patients with a prescription drug claim for atorvastatin in the index month, September 2005, were selected for inclusion. The resulting sample contained 453 409 unique patients. These patients were subsequently followed for 12 months to determine

drug and then generic or vice versa, the patient was counted uniquely only once in this calculation.

3. Patients switching to branded simvastatin: The count of unique patients who switched from atorvastatin to any milligram dose level of branded simvastatin within 12 months of the index period.

4. Patient switching to generic simvastatin: The count of unique patients who switched from atorvastatin to any milligram dose level of nonbranded simvastatin within 12 months of the index period. If the patient switched to the branded drug and then generic or vice versa, the patient was counted in this category and category 3.

Patients switching to simvastatin were also categorized by their dose level for atorvastatin in the index month and the dose level of the simvastatin they switched to, using the following criteria:

5. Patients switching to a specific dose of either branded or generic simvastatin from a specific dose of atorvastatin: The count of unique patients who switched from a specific dose of atorvastatin at index to a specific dose of either branded

and then to generic 20-mg simvastatin counts as 1 switch from 10-mg atorvastatin to 20 mg of either branded or generic simvastatin. Note that if a patient had multiple changes in dose levels of simvastatin during the study period, the patient was counted in each of the dose levels of simvastatin prescribed.

6. Patients switching to a specific dose of branded simvastatin from a specific dose of atorvastatin: The count of unique patients who switched from a specific dose of atorvastatin at index to a specific dose of branded simvastatin within 12 months of the index period. Note that if a patient switched to more than 1 dose level of branded simvastatin during the study period, the patient was counted in each of the dose levels of branded simvastatin prescribed.

7. Patients switching to a specific dose of generic simvastatin from a specific dose of atorvastatin: The count of unique patients who switched from a specific dose of atorvastatin at index to a specific dose of simvastatin within 12 months of the index period. Note that if a patient switched to more than 1 dose level of a generic simvastatin during the study period, the patient was counted in each of the dose levels of generic simvastatin prescribed.

The last 3 categories were used to classify patients as switching to either an equivalent-or-higher or a lower therapeutic dose.

Results

Among the 453 409 patients using atorvastatin at the beginning of the study, 56 919 (13%) switched to another statin (Table 2, switching category 1). The likelihood of switching was similar for patients taking 10 mg to 40 mg of atorvastatin at the start of the study (12%-14%), but somewhat lower for patients at the 80-mg dose (7%). A total of 13 530 patients (3% of all patients) switched to either branded or generic simvastatin by the end of the study period. Of these, 8537 patients switched to branded simvastatin and 9766 switched to generic simvastatin sometime during the year, indicating multiple changes of medication during the year for many patients (Table 2, switching categories 2-4).

Data on switches to simvastatin, either branded or generic, at specific dose levels (Table 2, switching category 5) show that a sizable portion of patients switched to a lower therapeutic dose of simvastatin. For example, patients switching from atorvastatin 20 mg should receive more than 20 mg of simvastatin to receive a therapeutic dose equal to or higher than their atorvastatin dose, given the higher efficacy of atorvastatin at milligram-equivalent doses. However, of the 5023 switches from atorvastatin 20 mg to either branded or generic simvastatin, 2168 (43%) were to a lower therapeutic dose(15 switches to 5 mg, 220 to 10 mg, and 1933 to 20 mg). A substantial percentage of patients switching from the 3 other dose levels of atorvastatin also received lower therapeutic doses. A similar pattern of switches to lower therapeutic doses occurred for branded simvastatin and for generic simvastatin (Table 2, categories 6 and 7, respectively).

The same data illustrate that some patients switched to more than 1 dose level throughout the study period. For example, although 4729 patients switched from atorvastatin 20 mg to simvastatin at any dose level (Table 2, category 2), there were a total of 5023 switches from atorvastatin 20 mg to either branded or generic simvastatin at the 5 dose levels (Table 2, category 5). Overall, 6% of patients switched to 2 or more dose levels of either branded or generic simvastatin (Table 3).

Data on switches to the various doses of simvastatin were summarized by whether the switch resulted in a lower therapeutic dose or an equivalent-or-higher dose (Table 4). Compared with the atorvastatin dose in the index month, 38% of switches to either branded or generic simvastatin resulted in a lower therapeutic dose. The percent of switches to a lower therapeutic dose was 18% for those switching from 10 mg, 43% for those switching from 20 mg, 73% for those switching from 40 mg, and 100% for those switching from 80 mg.

The results were also examined separately for switches to branded and generic simvastatin (Table 4). Compared with the atorvastatin dose in the index month, 41% of switches to branded simvastatin resulted in a lower therapeutic dose. The percent of switches to a lower therapeutic dose of branded simvastatin were 20% for those switching from 10 mg, 46% for those switching from 20 mg, 75% for those switching from 40 mg, and 100% for those switching from 80 mg. Compared with theatorvastatin dose in the index month, 36% of switches to generic simvastatin resulted in a lower therapeutic dose. The percent of switches to a lower therapeutic dose of a generic simvastatin were 16% for those switching from 10 mg, 40% for those switching from 20 mg, 70% for those switching from 40 mg, and 100% for those switching from 80 mg.

Discussion

In this study, pharmacy claims data from a large electronic database showed that, over a period of 1 year, 13% of patients receiving atorvastatin during the index month switched to another statin; and of those, 24% switched to either branded or generic simvastatin. Overall, nearly 40% of switches to simvastatin resulted in the patient receiving a lower therapeutic statin dose. The higher the atorvastatin dose during the index month, the greater the percent age of switches to a lower therapeutic dose of simvastatin: 18%, 43%, 73%, and 100% for atorvastatin 10 mg, 20 mg, 40 mg, and 80 mg, respectively. (The 100% for 80-mg atorvastatin reflects the fact that the maximum recommended daily dose of simvastatin is 80 mg.) This pattern was similar regardless of whether the switch was to branded or generic simvastatin.

cholesterol levels); and adverse effects. Nevertheless, the data suggest that a substantial proportion of patients switching from atorvastatin to simvastatin may be receiving suboptimal therapy. Further research is needed to determine the impact of switching on LDL-C and other lipid parameters, as well as on cardiovascular health.

Conclusion

A significant proportion of patients switching from atorvastatin to simvastatin received a lower therapeutic dose, which may have an adverse impact on quality of care and patients' health status. Further research is needed to assess the potential negative effect on patient outcomes.

Acknowledgments: Editorial support was provided by Pamela Mausner, MD, and funded by Pfizer Inc. Drs Hess and Hill are employees of Surveillance Data Inc. who are paid consultants in the development of the manuscript. This study was funded by Pfizer Inc.

Address correspondence to: Larry Z. Liu, MD, PhD, Director, Global Outcomes Research, Medical Division, Pfizer Inc, 325 East 42nd St, New York, NY 10017. E-mail: Larry.Liu@pfizer.com.

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