Treatment Failure With Atorvastatin After Change From Rosuvastatin to Atorvastatin

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.

Results

Three hundred twenty-three patients were identified and reviewed as converted from rosuvastatin to atorvastatin during the study period with no prior use of atorvastatin. Of the 323 charts that were reviewed, 195 patients met the study inclusion criteria and were analyzed for rate of treatment failure in terms of lipid goals and rate of AEs. Twenty of 195 patients (10.3%) were no longer at their LDL-C goal after conversion from rosuvastatin to atorvastatin. Of those 195 patients, 29 (14.9%) experienced an adverse drug reaction (ADR) as a result of atorvastatin treatment that was severe enough to result in discontinuation of the drug and switching the patient back to the originally prescribed dose of rosuvastatin. Figure 1 illustrates the number of patients and documented atorvastatin ADRs. The most common ADR documented to atorvastatin was myalgias (8.2%).

The average change in lipid levels was calculated and atorvastatin therapy was found to result in clinically insignificant changes to the lipid panel (Table 2). A 2-tailed paired t test was used to assess the statistical significance of these changes. Atorvastatin therapy resulted in an average decrease of LDL-C by 5.0 mg/dL ( P < .01) in comparison to previous therapy with equivalent rosuvastatin dose. Other noted changes to lipid profile after formulary conversion included TG reduction by 2 mg/dL ( P = .69), TC increased by 0.58 mg/dL ( P = .80), and HDL-C reduction by 4.66 mg/dL ( P < .01).

Although the decrease in LDL-C and HDL-C as a result of the formulary change was found to be statistically significant, they are not thought to result in a clinical difference. Clinically and statistically insignificant changes in liver enzymes and CPK were also discovered as a result of atorvastatin therapy conversion (Table 3). Atorvastatin therapy resulted in an averaged decrease of aspartate aminotransferase by 2.2 IU/L ( P = .19) and an increase in alanine aminotransferase by 1.4 IU/L ( P = .47). Average change in CPK was -6 IU/L ( P = 89).