Understanding Practice Patterns and Low-density Lipoprotein Cholesterol Goal Attainment Implications of Switching Patients From Simvastatin in a Health Plan Setting

Objective: To understand the practice patterns and National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal attainment rates after switching patients from simvastatin (SMV) to other statins or the combination of SMV and ezetimibe (EZE).

Methods: This retrospective study linked claims and laboratory data from a national health plan. Patients were included if they were taking SMV and were switched to other statins or a fixed-dose combination of SMV and EZE between July 1, 2005, and June 30, 2006. Patients taking dual SMV/EZE before switch were excluded from the study.The NCEP ATP III risk status of patients at switch was assessed based on medical claims, pharmacy claims, and laboratory values in the 12-month preswitch period. Lipid data (available on a patient subset) were used to estimate patients’ goal attainment status at and after switch.

Results: Of 134 168 patients taking SMV, 11 929 (8.9%) switched to other statins or SMV/EZE. The mean age of switching patients was 54 years (standard deviation, 9 years), 61% were men, 50% were high risk, and 30% were moderate risk. The mean time to switch among new starters of SMV (n = 3379) was 77 days. Forty percent (n = 4772) of the total switches occurred among those taking the lower doses (5, 10, and 20 mg) of SMV. Most patients switched from SMV to SMV/EZE (60.5%), followed by atorvastatin (17.3%), rosuvastatin (10.1%), lovastatin (8.6%), pravastatin (2.9%), and fluvastatin (0.7%). Similarly, most patients switching from higher doses of SMV switched to SMV/EZE (52.5%), followed by atorrestatin (21.1%) and rosuvastatin (10.1%). Overall, 55.6% (758 of 1362) of patients were at ATP III goal at the time of switch from SMV (across all doses; n = 758), and 56.1% (292 of 521) of those taking lower doses were at goal at time of switch. A majority (69.9%) of patients who were at goal and switched from SMV (across all doses) were switched to SMV/EZE, and 61.6% of those at lower doses of SMV switched to the combination drug. Of patients who were not at goal at switch (n = 604), 73.3% attained ATP III LDL-C goal after switch. The mean percent LDL-C reduction that was needed to attain LDL-C goal at switch from SMV (n = 604) was 18.1%.

Conclusions: There is an opportunity to further increase LDL-C goal attainment rates among patients switched from SMV. The clinical, prescription benefit design, and economic implications of the finding that a majority of patients are at goal when switched from SMV and a majority of patients are being switched from SMV to SMV/EZE need to be further examined.

(Am J Manag Care. 2007;13:S276-S281)

In conjunction with diet and exercise, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors (statins) are the recommended therapy for reducing low-density lipoprotein cholesterol (LDL-C) and are the most widely used agents in the treatment of dyslipidemia.^1,2 Several statins have been extensively studied and have been shown to reduce cardiovascular morbidity and mortality.^3-11 Although no cardiovascular morbidity or mortality data with rosuvastatin are currently available, clinical studies examining the impact of rosuvastatin on cardiovascular events and mortality are currently being conducted.¹² Similarly, the effects of ezetimibe given either alone or in addition to an HMG-CoA reductase inhibitor or fenofibrate on cardiovascular morbidity and mortality have not yet been established.¹³

A significant development in the statin marketplace in 2006 was the availability of a generic form of simvastatin (SMV), with the first generic version approved in June 2006.¹⁴ This has afforded a significant opportunity to clinicians and payers to provide effective and efficient dyslipidemia care for the appropriate patient groups.^15,16 To deliver quality care with the effective use of resources, it is important to understand the pattern of switching patients from SMV to other statin therapies including a fixed-dose combination of SMV and ezetimibe (EZE). In addition, it will also be valuable in further understanding the rationale and the effectiveness of switching in terms of National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III goal attainment criteria. The aim of the present study was to evaluate patterns of switching from SMV and NCEP ATP III goal attainment rates among switched patients in a large national health plan enrollee population.

Methods

Data Source. This retrospective analysis linked medical claims, pharmacy claims, enrollment information, and laboratory data from a large national health plan. The claims data were submitted by physicians, facilities, and pharmacies for payment of services provided to covered commercial, Medicare Advantage, and Medicaid health plan members. The database includes approximately 14 million covered lives annually with both medical and pharmacy coverage. Data were de-identified and met the requirements for the protection of private health information in accordance with the Health Insurance Portability and Accountability Act of 1996.¹⁷

Identification of SMV Switchers. All patients aged 18 years or older with a dispensing (ie, prescription fill) for SMV between July 1, 2005 and June 30, 2006 were identified. Switchers were defined as those patients prescribed another statin or a fixed-dose combination of SMV/EZE during the same period after a monotherapy SMV dispensing. Patients taking dual SMV/EZE therapy before the switch were excluded from the study sample. Variable follow-up observation was permitted until disenrollment. Patients were considered new users of SMV if they had no prior use of SMV within a year; continuing users were those for whom no gap in therapy during the 12-month baseline period was observed. The subsets of patients with qualifying LDL-C laboratory results in both the preswitch and postswitch periods were identified for the analysis of NCEP ATP III goal attainment. The baseline LDL-C value was defined as the LDL-C value within 6 months before switch. The follow-up LDL-C value was defined as LDL-C value after 30 days of switch. If multiple LDL-C values were available in each baseline and postswitch periods, then an average LDL-C value was estimated.

NCEP Risk Groups. In accordance with NCEP ATP III guidelines,¹¹ patients were classified into risk categories. The presence of risk factors was determined from diagnoses on medical claims, filled prescriptions on pharmacy claims, and cholesterol laboratory results in the 6-month preindex period. Each risk factor was identified and patients were categorized into risk groups based on the number and combination of risk factors present. The highrisk group included those with administrative data codes for myocardial infarction, ischemic heart disease, cerebral vascular accident, transient ischemic attack, coronary artery bypass graft, angioplasty, peripheral vascular disease, or diabetes. High-risk patients had a target LDL-C goal of <100 mg/dL. Moderate risk was defined as the presence of at least 2 of the following 3 risk factors: hypertension (International Classification of Diseases, Ninth Revision code and pharmacy claim for antihypertensive agents), age (men of ages ≥45 years and women of ages ≥55 years), or preindex high-density lipoprotein cholesterol <40 mg/dL. Patients in the moderate-risk group had a target LDL-C goal of <130 mg/dL. Patients in the low-risk group (<2 risk factors) were assigned a target LDL-C goal of <160 mg/dL. Because the NCEP-defined risk factors of smoking status and family history of premature coronary heart disease (CHD) cannot be obtained accurately from administrative claims, these risk factors were not included in the risk tratification process. Similarly, the Framingham risk score could not be computed based on available data.

Analysis. This was a descriptive analysis to explore the pattern of switching and NCEP ATP III goal attainment status among patients treated with SMV. The switching patterns from SMV to other statins or SMV/EZE and by SMV dose were determined. The percentage of patients who were at NCEP goal at the time of switch from SMV, as well as the percentage of patients who attained NCEP goal after switching from SMV, were also estimated.

Results

Patient Characteristics. Of the approximately 14 million enrollees with data contained in the research database during the period from July 1, 2005 through June 30, 2006, a total of 134 168 patients had a dispensing for SMV. A total of 11 929 (8.89%) patients switched to another statin during this same period (Figure 1). The mean age of patients was 53.79 years (standard deviation, 8.65 years), and 61% were men (Table 1). Fifty percent of patients switching from SMV to another statin were at high risk for CHD, 20% were at moderate risk, and 30% were at low risk (Table 1). Most patients were prescribed a 20-mg (34.31%) or 40- mg (46.62%) dose of SMV before switching. Patient characteristics were similar between the full sample and the subsample with LDL-C results (Table 1).

Switching by Dose of SMV. As shown in Table 2, the most common switch from SMV (n = 11 929) was to SMV/EZE (60.54%), followed by atorvastatin (17.26%), rosuvastatin (10.05%), and lovastatin (8.60%). Only a small percentage of patients (3.55%) switched to pravastatin or fluvastatin. Of the total patients switched, 40% were switched from a low-dose (5, 10, or 20 mg) SMV. At every dose of SMV, patients were most likely to switch to SMV/EZE (46.43% at 5 mg; 47.67% at 10 mg; 53.26% at 20 mg; 65.11% at 40 mg; and 68.80% at 80 mg SMV). Fifty-two percent (2503 of 4772) of patients switched from low doses of SMV to SMV/EZE. Of these 2503 patients who switched from low-dose SMV to SMV/EZE, 8.35% were switched to 10-mg EZE/10-mg SMV, 60.41% were switched to 10-mg EZE/20-mg SMV formulation, 29.44% switched to 10-mg EZE/40-mg SMV, and 1.80% switched to 10-mg EZE/80-mg SMV formulation.

Switching by LDL-C Goal Status Before Switch. A total of 1362 switching patients (of the total 11 929 SMV switchers, 11.42%) had available baseline and follow-up LDL-C results. At the time of the switch, 55.65% of these patients (n = 758) were at NCEP ATP III goal. Forty-six percent of patients who were at goal at the time of switch were considered to be at low risk for CHD, 19.92% were at moderate risk, and 34.30% were at high risk. Among patients not at goal at time of switch (n = 604), 14.40% were at low risk, 17.22% were at moderate risk, and 68.38% were at high risk. Of SMV users already at goal before switching therapy, close to 70% switched to SMV/EZE, 13% switched to atorvastatin, and 7.92% to rosuvastatin (Figure 2, Table 3). Similarly, 67% of patients not at goal at switch switched to SMV/EZE, 15.56% switched to atorvastatin, and 8.28% switched to rosuvastatin (Figure 3, Table 3).

Goal Attainment After Switch From SMV. Of patients who were not at goal at switch, the mean percent reduction in LDL-C needed to attain NCEP goal at time of switch was 18.06%. Of these patients, 73.34% attained NCEP goal after switch. Among these patients (not at goal at time of switch and then achieving goal after switch), a mean percent reduction required at time of switch was 15.72%, whereas those not at goal after switch required a 24.50% reduction to reach goal.

Limitations

In this study, 9% of SMV users switched to another statin in the course of a 1-year observation time frame. For health plans and clinicians aiming to achieve efficient and effective management of dyslipidemia, this highlights a need to better understand the patterns and clinical outcomes of switching patients from SMV to other alternatives. This study provides a descriptive summary of the trends in switching from SMV and the associated goal attainment outcomes.

In the present study, across all SMV doses, the most common switch from SMV was to SMV/EZE. In addition, of the patients switched from lower doses (5, 10, and 20 mg) of SMV, a large majority of them switched to SMV/EZE. Although it was not possible to determine the reasons for the switch, this is an interesting finding and indicates the need to determine the reason why patients were switched from a low dose of SMV to a combination of SMV and EZE as opposed to titrating to a higher dose of SMV. If tolerability to SMV was a reason behind the switch, then it makes clinical sense to switch to a non-SMV statin (eg, atorvastatin or rosuvastatin). However, it was observed that quite a few switches from lower doses of SMV were to SMV/EZE combinations without trying higher doses of SMV (including the 40-mg dose). Switches from lower doses of SMV to atorvastatin (21.12%) or rosuvastatin (10.05%) were also observed but to a much lesser extent compared with switches to SMV/EZE. Individual health plans and providers may have an interest in understanding the rationale for switching from lower doses of SMV to SMV/EZE combination, as well as evaluating the potential quality of care and economic consequences of switching from SMV in their local setting.

The study period only allowed switching pattern observation during the time period in which branded SMV was available. Future research should examine if the observed SMV switching patterns and trends change significantly with the availability of generic forms of SMV.

The analysis indicated that more than half of switching patients had already attained NCEP ATP III LDL-C goal at the time of switch. One of the potential reasons for switching patients who were already at goal could be adoption of more aggressive LDL-C targets11 by clinicians or tolerability issues with SMV. It is important to further determine the actual rationale behind switching these patients. The findings indicate that close to 70% of the patients who were already at goal at baseline were switched to SMV/EZE. Understanding the clinical rationale and clinical and economic implications of switching these at-goal patients from SMV to SMV/EZE may be important to providers in meeting their goal of providing effective and efficient management of dyslipidemia.

The study results highlight an opportunity to further increase LDL-C goal attainment rates among patients switched from SMV. Of those patients not at goal at switch, 73% of patients attained NCEP ATP III goal after switching to another agent. This may indicate that more effective treatment strategies (including more effective combination treatment strategies) may help to further improve the rate of goal attainment in these patients. Due to limited sample size, a comparison of individual statin-specific goal attainment rates after switch from SMV could not be estimated and this highlights further areas of research.

Conclusion

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6. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357.

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14. US Food and Drug Administration. FDA news release: FDA approves first generic simvastatin. June 23, 2006 [updated July 5, 2006]. Available at: http://www.fda.gov/bbs/topics/NEWS/2006/NEW01394.html. Accessed July 10, 2007. 15. Kamat S, Gandhi SK, Davidson M. Comparative effectiveness of rosuvastatin versus other statin therapies in patients at increased risk of failure to achieve low-density lipoprotein goals. Curr Med Res Opin. 2007;23:1121-1130.

17. US Department of Health & Human Services Office for Civil Rights. HIPAA: Medical Privacy—National Standards to Protect the Privacy of Personal Health Information. Last modified May 16, 2006. Available at: http://www.hhs.gov/ocr/hipaa/finalreg.html. Accessed April 13, 2007.

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