Treatment Failure With Atorvastatin After Change From Rosuvastatin to Atorvastatin
Due to the growing number of drug shortages and increasing cost of medications, large-scale formulary conversions are becoming more common and necessary for pharmacies to stay within their budget allocations. Statins are widely recognized as first-line therapy for cholesterol lowering and have been proven to reduce cardiovascular morbidity and mortality.1-5 In addition to statin therapy, weight loss and lifestyle changes are often necessary to meet optimum low-density lipoprotein cholesterol (LDL-C) goals.6 According to the Adult Treatment Panel III (ATP III) guidelines, the optimum LDL-C for each patient varies based on the presence of coronary artery disease (CAD), CAD risk equivalents, and other risk factors.7 Patients with CAD or CAD risk equivalents have an LDL-C goal of < 100 mg/dL. Those with multiple risk factors have an LDL-C goal of < 130 mg/dL, and those with 0 to 1 risk factors have an LDL-C goal of < 160 mg/dL.1-3,7,8
Numerous trials have compared the safety and efficacy of the 3-hydroxy-3-methylglutaryl-coenzyme A inhibitors, stating that rosuvastatin 5 to 10 mg per day is equivalent to 20 mg per day of atorvastatin in terms of its ability to lower LDL-C levels.7,9-14 The LUNAR (Limiting Under treatment of lipids in Acute coronary syndrome with Rosuvastatin) study compared the efficacy of rosuvastatin with that of atorvastatin in decreasing LDL-C in patients with acute coronary syndrome.8 Rosuvastatin 40 mg was significantly more successful in lowering LDL-C and increasing high-density lipoprotein cholesterol (HDL-C) compared with atorvastatin 80-mg daily therapy.
In October 2012, the national VA Pharmacy Benefits Management (PBM) Services released guidance regarding the conversion from rosuvastatin to atorvastatin, including the dosing conversion (Table 1), stating that rosuvastatin 5 mg daily should be considered equivalent and converted to atorvastatin 20 mg daily. In general, adverse events (AEs), such as increased liver enzymes, myopathies, and increased creatinine phosphokinase (CPK), are considered a class effect of the statins.13,14
Related: Statins showed no benefit in reducing risk of recurrent VTE
The recent 2013 American College of Cardiology/American Heart Association (ACC/AHA) Blood Cholesterol Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults has identified a large number of patients as candidates for high-intensity statins, which the authors defined as atorvastatin and rosuvastatin.4 These guidelines do not recommend LDL-C goals and instead use a risk calculator to determine which intensity of statin therapy is appropriate for certain patients. This change in practice will lead to a higher volume of high-intensity statin prescriptions and higher drug costs for some medical centers. Given the volume of prescriptions and the increased use of large-scale formulary conversions to reduce costs, more research is warranted to ensure equivalent dosing. With more data available and equivalent dosing defined, pharmacists may be better able to improve clinical results in patients that are included in these large-scale formulary conversions.
Methods
A retrospective chart review was performed on all LDL-C levels in patients receiving atorvastatin therapy due to the formulary conversion from rosuvastatin to atorvastatin at the Huntington VAMC (HVAMC) in Huntington, West Virginia, per the guidance published by the national VA PBM Services. The number of patients not at their LDL-C goal (as defined by ATP III guidelines) as a result of atorvastatin therapy was determined. Furthermore, AEs due to atorvastatin therapy such as increased liver enzymes, myopathy, and increased CPK were identified and analyzed.
The primary endpoint of this study focused on the rate of treatment failure in LDL-C reduction with atorvastatin treatment in patients previously at their LDL-C goal, as defined by the ATP III guidelines, with rosuvastatin therapy. Secondary endpoints included rate of AEs due to atorvastatin therapy, percentage increase in CPK and liver enzymes as a result of atorvastatin therapy, and percentage LDL-C, HDL-C, total cholesterol (TC), and triglyceride (TGs) changes since conversion from rosuvastatin to atorvastatin.
Patients were included in the study if they were aged 18 to 89 years, previously at LDL-C goal with rosuvastatin therapy for at least 3 months, had never previously received atorvastatin, were converted to atorvastatin therapy as a result of a large-scale formulary conversion at HVAMC, and had a fasting lipid panel completed 1 to 6 months after conversion. Patients were excluded from the study if they received other lipid-lowering medications (eg, bile acid sequestrants, fibrates, niacin, or ezetimibe) in the 12 months before or after receiving statin therapy, had previously documented AEs (eg, myopathy, increased liver enzymes, increased CPK as a result of statin therapy, or history of known homozygous familial hypercholesterolemia) current active liver disease (ALT > 2x ULN [upper limit of normal]), unexplained CPK ≥ 3x ULN, serum creatinine (SCr) > 2 mg/dL, or history of alcohol or drug abuse within the last 5 years.
