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Therapeutic Interchange Process
Interchange from rosuvastatin to atorvastatin was expected to provide about $643,000 annually in drug cost savings to NF/SGVHS while providing equivalent therapy. The cost for a 30-day supply of rosuvastatin was about $22.56 at the time of interchange, and a 30-day supply of generic atorvastatin was $1.77.The interchange from rosuvastatin to atorvastatin was approved by the Pharmacy and Therapeutics Committee Meeting on August 8, 2012, and began shortly thereafter. Interchanges were halted temporarily in November 2012 due to a shortage of manufacturer supply, but the process fully resumed in January 2013 once the drug shortage resolved. Direction was provided to VA facilities by a guidance letter issued through PBM leadership.8 The interchange used a standard interchange guide to complete the process (Table 2).
Posttherapeutic Interchange Analysis
Researchers conducted an internal pharmacy computerizedprescription records search to identify VA outpatients who were converted from rosuvastatin to atorvastatin from February 1, 2012, to August 1, 2013. A total of 202 patients were randomly selected and included in this retrospective chart review. Investigators analyzed data points for safety and efficacy, including liver function tests (LFTs), lipid panels, and ADR reports. This information was obtained from laboratory data, vital signs, allergy information, ADR data, and progress notes using CPRS. Two sets of laboratory data were obtained for research purposes, the most recent laboratory values pre-interchange and the most recent laboratory values postinterchange to atorvastatin.
Investigators determined whether patients were converted to an equivalent dose of atorvastatin through an assessment of the most recent dosage of rosuvastatin before the interchange and the dosage of atorvastatin postinterchange. Researchers also analyzed refill history and interacting medications to assess possible confounding factors. Medication adherence was assessed via refill history. Medication adherence was defined as a medication possession ratio of at least 70%, which correlated to receipt of 3 or more 90-day supplies in the year prior to interchange. The above data were collected via retrospective chart review and entered into a spreadsheet.
Statistics
All identifying information was removed from the data set prior to statistical analysis. The data analysis for this project was generated using SAS/STAT software, version 9.3 of the SAS System for Linux x64 (SAS Institute, Cary, North Carolina).
Researchers assumed an equal variance in preinterchange and postinterchange lipid and liver panel values. Preinterchange and postinterchange lipid values (LDL-C, HDL-C, total cholesterol [TC], and triglycerides [TGs]) and liver values (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], and creatinine phosphokinase [CPK]) were analyzed by paired t test. All values were reported as mean (SD), and significance was defined as P < .05.
Results
More than 6,000 veterans within the NF/SGVHS were identified as eligible for the interchange. Of those who were converted, 202 patient records were randomly selected and reviewed. Patient population characteristics are summarized in Table 3. Most patients were aged > 65 years (61.4%) with an average body mass index (BMI) of 32.4. Most patients were converted to the correct corresponding dose of atorvastatin (82.7%) and achieved adherence with statin therapy (84.2%). There was no difference in pre- and postinterchange adherence detected as a result of this review.
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Adverse drug reactions were documented in 16 cases, accounting for 8% of the study population. The most commonly reported ADR was myalgia or arthralgia, which was found in 10 cases (5%). Other ADRs identified in this retrospective review included treatment failure, nausea, vomiting, abdominal discomfort, abnormal liver enzymes, nasopharyngitis, and pruritis (Table 4). Of note, treatment failure was determined on a case-by-case basis but was generally defined as a failure to reach LDL-C goal (< 100 mg/dL or < 70 mg/dL), despite titration of atorvastatin. Interacting medications were identified in 30.7% of patients; however, no reported ADRs were associated with interacting medications. The most common drug interaction was concomitant niacin, followed by antiarrhythmics (ie, amiodarone, diltiazem, etc), and fibrates (ie, gemfibrozil, fenofibrate). All potentially interacting medications identified in this retrospective chart review are compiled in Table 5.
No significant difference between mean pre- and postinterchange lipid panel values was identified in this retrospective chart review (Table 6). In addition, no significant difference was detected in pre- and post-interchange AST, ALT, and CPK values (Table 7). However, a statistically significant increase in ALP was detected, with a mean ALP of 73.33 IU/L prior to interchange and 83.64 IU/L postinterchange (P < .0001).
Discussion
The goal of this retrospective observation was to ensure that safety and efficacy were not compromised as a result of this cost-saving therapeutic interchange. No differences in liver enzymes (safety) and lipid control (effectiveness) were observed in this study. There were no statistically significant changes to the lipid panel or liver panel detected with the exception of ALP. The reason for this statistically significant increase is unknown; however, it may support the hypothesis of variation in hepatocellular effects between the statins due to lipophilic properties.3,6 In general, liver enzymes can be affected by extrahepatic functions. Serum ALP and other liver enzymes can be affected by bone disease, abdominal adiposity, alcoholism, and other concomitant diseases.10 No comorbid conditions were assessed, thus differences in liver enzymes may not be fully attributable to statin therapy. This retrospective review found no clinically significant effect correlated with the increase in ALP.