Therapeutic Interchange From Rosuvastatin to Atorvastatin in a Veteran Population

Patients with known cardiovascular (CV) disease are at greater risk for CV events.¹ Hydroxymethylglutaryl-CoA (HMG Co-A) reductase inhibitors, or statins, have been shown to reduce CV events and to reduce all-cause mortality.^1,2 Thus, these agents should be a standard approach to secondary prevention of CV events.^1,2 Although the main function of statins is to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, trials have shown that other lipid-lowering agents have reduced the incidence of CV events but have failed to show any difference in mortality.¹ Thus, the therapeutic effects of statins may be a result of “pleiotropic” effects in addition to a reduction in LDL-C.³

As a result, prescribing practices and professional society guidelines have deferred to statins as a first-line choice for lipid-lowering therapy.¹ Although each statin varies in its ability to lower LDL-C and inhibit HMG Co-A reductase, as a class, statins have been proven to be safe and efficacious in reducing LDL-C, decreasing risk of coronary artery disease, and decreasing mortality.

The 2013 American College of Cardiology (ACC) and American Heart Association (AHA) guideline on the treatment of blood cholesterol to reduce CV risk in adults resulted in a major shift in clinical practice recommendations. The focus of treatment has changed from LDL-C and TC goals to stratifying patients to either high-intensity or moderate-intensity statin therapy, based on their comorbidities and risk of atherosclerotic CV disease (ASCVD).¹ Primary prevention of CV disease has been proposed for patients with diabetes mellitus aged 40 to 75 years, familial hypercholesterolemia (LDL-C > 190 mg/dL), and for patients with an ASCVD risk score > 7.5%. Secondary prevention has been proposed for all patients with a history of ASCVD. Among the available choices for intensive statin therapy, the 2 most potent regimens are atorvastatin (40-80 mg) and rosuvastatin (20-40 mg) daily. The ACC/AHA guideline recommends high-potency therapy with either rosuvastatin or atorvastatin with equal preference.¹

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Statin therapy is generally well tolerated; however, the use of statins is not without risk of adverse drug reactions (ADRs). Skeletal muscle discomfort has been reported in 4% to 10% of patients taking either atorvastatin or rosuvastatin.^4,5 Liver enzyme abnormalities are less common, having been reported in only about 2% to 3% of patients taking either atorvastatin or rosuvastatin.^4,5 Although muscle-related intolerance and liver enzyme abnormalities are considered to be class effects, research speculates that the therapeutic and safety effects of statins may differ, based on tissue solubility.^2,6 Variability in the myotoxic and hepatotoxic effects of statins has been attributed to differences in tissue solubility, hypothesizing that lipophilic statins are more easily taken up into myocytes and hepatocytes, resulting in an increase in toxic effects.^2,6

This study assessed differences in therapeutic and safety endpoints resulting from the recent interchange from rosuvastatin to atorvastatin within the North Florida/South Georgia Veterans Health System (NF/SGVHS). Although both these agents are high-potency HMG Co-A reductase inhibitors and share a mechanism of action, they have pharmacokinetic differences, including a key difference in tissue solubility (Table 1).

With the availability of low-cost generic atorvastatin in early 2012, the VA Medical Advisory Panel and Pharmacy Benefits Management (VA MAP/PBM) added atorvastatin to the VA National Formulary as the preferred high-potency statin.^7,8 Before October 2012, rosuvastatin had been the preferred high-potency statin within the VA. With support from VA MAP/PBM leadership, NF/SGVHS instituted an interchange from rosuvastatin to atorvastatin for cost-savings purposes.⁹

Before the interchange, the records of patients were reviewed to determine whether justification existed for continued use of rosuvastatin. Patients were converted to atorvastatin if deemed appropriate and received education and consultation through direct patient contact or a letter regarding the interchange. Justifications for continued use of rosuvastatin included documentation of an atorvastatin ADR, active liver disease, or patients taking cyclosporine or certain protease inhibitors.⁸

The objective of this retrospective evaluation was to assess the efficacy and safety of the interchange from rosuvastatin to atorvastatin within NF/SGVHS. The results of this review are helpful to confirm the efficacy and safety of the interchange and identify any differences in efficacy and safety that may have occurred as a result of the interchange to a different high-potency statin. For this review, statin efficacy was assessed via review of pre- and postinterchange lipid panel values, assessing for a significant difference between equipotent atorvastatin and rosuvastatin therapy. Similarly, safety was assessed by analysis of pre- and postinterchange liver enzyme panels and assessing for significant differences as a result of the interchange.

Methods

The therapeutic interchange was conducted within the NF/SGVHS, which provides patient care at hospitals in Gainesville, Florida, and Lake City, Florida, and 11 outpatient clinics located throughout North Florida and South Georgia. Like other VA facilities, NF/SGVHS uses Computerized Patient Records System (CPRS) to electronically integrate all clinical patient information, including medical progress notes, consults, admission and discharge summaries, allergies and ADRs, patient problem lists (diagnoses), vital signs, medication orders, and laboratory test results. Approval to conduct this study was granted by the University of Florida Investigational Review Board and the Research and Development Committee at NF/SGVHS.