Lipid Management When Converting Fluvastatin to Pravastatin: Medication Use Evaluation
There were no signifi cant differences in mean low-density lipoprotein cholesterol levels after patients were converted from fl uvastatin to pravastatin therapy.
In 2001, the National Cholesterol Education Program (NCEP) published guidelines regarding the “detection, evaluation, and treatment of high blood cholesterol in adults.”1 The NCEP updated the Adult Treatment Panel (ATP) III guidelines in 2004 to provide more stringent low-density lipoprotein (LDL) cholesterol goals compared with the previous guidelines.
summarizes the 2004 update providing recommendations for LDL goals, therapeutic LDL options, and when medication therapy should be added to lifestyle modifi cations.1
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor class, also known as statins, have been shown to be the most effective in lowering LDL cholesterol. This class of medication has been shown to decrease morbidity and mortality in patients at risk for cardiovascular events. Each statin medication has a different effect on the amount of LDL reduction. The ATP III guidelines provide standard doses of the currently available statin medications to reduce LDL by 30% to 40%. An LDL reduction of 34% has been seen with pravastatin doses of 40 mg per day, while an LDL reduction of 35% has been seen with fl uvastatin doses of 80 mg per day.1 This information indicates a probable dosing ratio of 2:1 (fl uvastatin to pravastatin) when converting patients’ lipid therapy.
Veterans Affairs (VA) patients may be converted to a new therapy based on changes to the VA national formulary. This formulary may be updated due to changes in safety or effi cacy as determined by new evidence from clinical studies or changes in cost. In August 2007, VA Medical Centers switched patients formerly on fl uvastatin to pravastatin for cost avoidance.
summarizes the conversion of fl uvastatin to pravastatin.2
A study by Jacotot and colleagues followed 134 patients randomized to double-blind, double-placebo treatment beginning with either fl uvastatin 40 mg or pravastatin 20 mg for 16 weeks. During the fi rst 4 weeks of the study, patients received either medication dosed once daily. For the last 12 weeks of the study, fluvastatin patients were increased to 40 mg twice daily and pravastatin patients were increased to 40 mg daily. During the initial 4 weeks of treatment, fluvastatin 40 mg daily and pravastatin 20 mg daily were equally efficacious in lowering LDL levels. At the end of 16 weeks of treatment, a significant difference was found with fluvastatin 40 mg twice daily versus once daily, with LDL decreasing by 30.4% (P <.001). Among patients taking pravastatin 40 mg daily, LDL decreased by 26.6% but the decrease was not found to be statistically significant. Liver function tests (LFTs) and creatine phosphokinase (CPK) levels were monitored, and no abnormalities were observed throughout the study.3
The primary objective for this retrospective study was to determine whether conversion of fluvastatin to pravastatin therapy results in comparable LDL-lowering effects.
This study was a retrospective chart review of VA patients converted from fluvastatin to pravastatin. The VA prescription database VISTA was used to evaluate prescription reviews followed by use of the Computerized Patient Record System to conduct medical chart reviews. The Administrative Officer used the FileMan program to extract the names of all patients who were converted from fluvastatin to pravastatin during the conversion. Patient data were collected and included diagnosis of diabetes per chart problem list, prescription number, LDL, total cholesterol (TC), triglycerides (TGs), highdensity lipoprotein (HDL) cholesterol, alanine aminotransferase, aspartate aminotransferase, and CPK levels, and incidence of possible adverse events. Adverse events were defined as a change in statin therapy after the conversion as documented in the patient’s chart, an abnormal LFT result (defined as >3 times the upper limit of normal), an abnormal level of CPK (defined as >10 times the upper limit of normal), or a documented drug allergy to pravastatin.
Patients meeting the defined inclusion and exclusion criteria were included. The number of patients was predefined by the conversion that had already taken place. Only patients of the VAMC and associated Community- Based Outpatient Clinics (CBOCs) with a measured fasting lipid panel 24 weeks prior to the conversion and a measured fasting lipid panel between 6 and 24 weeks after the conversion of fluvastatin to pravastatin met the inclusion criteria. Exclusion criteria included patients not from the VAMC or associated CBOCs, patients on multiple medications for dyslipidemia, patients not meeting their LDL goal previously on fluvastatin, lack of a fasting lipid panel 24 weeks prior to the conversion or between 6 and 24 weeks after the conversion, or patients not following the dosing conversion as provided. The LDL goals were determined by 2004 ATP III guidelines. There was no compensation for patients who participated in this study. Patient privacy was protected by assigning each patient a unique identification number consisting of the patient’s pravastatin dose and an assigned sequential ending number (eg, 20prava-1). The patient identifiers were promptly destroyed by placing in VAMC shred bins after the unique ID had been created for each patient.
The primary end point of this study was to compare mean LDL levels of fluvastatin and pravastatin therapy following a conversion. The secondary end points were to compare mean TC, TG, and HDL levels between fluvastatin and pravastatin therapy; to compare the percentages of type 2 diabetes mellitus (T2DM) patients who were at the desired LDL goal between the 2 statin groups; and to assess the incidence of adverse events following the conversion to pravastatin therapy.
The primary end point was assessed using the paired t test to compare the preconversion and postconversion mean LDL levels ± the standard deviation. A significant difference from the null hypothesis was defined as a 2-sided α of .05. The secondary end points were assessed using the paired t test to compare the preconversion and postconversion mean levels of TC, TGs, and HDL ± the standard deviation and to assess the differences in T2DM patients who achieved their LDL goal with fluvastatin therapy versus pravastatin therapy.
The VAMC and associated CBOCs converted a total of 369 patients from fluvastatin to pravastatin. Of the 369 patients, 70 patients met the inclusion criteria (
). All of the 70 included patients were male, with 17 patients having a diagnosis of T2DM. The remaining patients were excluded due to not following the dosing conversion, concomitant dyslipidemic therapy, lack of lipid panels 24 weeks before the conversion or 6 to 24 weeks after the conversion, or not meeting their LDL goal with fluvastatin therapy.
Following the conversion, LDL levels did increase by an average of 4 mg/dL; however, these results were not statistically significant among all 70 patients (P = .093), as well as among the patients receiving maximized pravastatin therapy (P = .311). The conversion resulted in statistically significant differences in TC, TGs, and HDL with P = .001, .045, and .008, respectively (
). TC and TG levels were less well controlled and HDL levels were more controlled with pravastatin therapy. Only the improvement of HDL was considered clinically significant, because patients achieved their HDL goal with pravastatin therapy. Although there was a significant difference in TC and TG values, patients generally remained at goal after the conversion. Most patients had no change with respect to remaining at their lipid panel goals after the conversion: 62.9% (LDL), 87.1% (TC), 80% (TGs), and 80% (HDL).
For patients on maximum statin therapy, the conversion from fluvastatin to pravastatin resulted in statistically significant differences in TC and HDL. These changes may not be considered clinically significant, as patients remained at goal. The largest change in mean lipid panel values occurred with TGs (+18.57 mg/dL), though this change was not found to be significant.
For T2DM patients, the conversion from fluvastatin to pravastatin resulted in no statistically significant differences in all lipid parameters. Most of the T2DM patients (88%) remained at their LDL goal after the conversion.
The adverse drug reactions were documented when reviewing all pravastatin-converted patients (n = 369). Myalgias were reported per patient charts in 4 patients, gastrointestinal disturbances in 2 patients, rhabdomyolysis in 1 patient, dizziness in 1 patient, and increased LFTs in 1 patient. There was a 2.44% incidence of total adverse drug reactions in the pravastatin group.
The purpose of the study was to provide information regarding future formulary conversions from the standpoint of cost avoidance. As anticipated, the conversion to pravastatin did not provide significant improvements in the lipid panel. In addition, these results were not statistically significant either for the total population or for the maximum therapy and diabetic subgroups (P = .093, .311, and .387, respectively). Although LDL slightly increased, the increase was not considered to be clinically significant, as 80% of total patients and 88% of the T2DM patients remained at their LDL goal after the conversion. For patients who did not remain at their LDL goal, either an increase in dose or trial of a more potent statin could be considered. All results were comparable following the conversion of fluvastatin to pravastatin therapy, with a total cost savings of $8574.11 for the Martinsburg, West Virginia, VAMC. These results may be interpreted based on clinical significance, because a 1% reduction in LDL can result in a 1% decrease in coronary artery disease events. In addition, a 1 mg/dL reduction in HDL can result in a 2% to 3% increase in coronary artery disease events.1 It was not the purpose of the study to evaluate cardiovascular events based on changes in lipid panels.
As this study was a retrospective chart review, there are several limitations. First, the exact date that pravastatin therapy began might have varied by patient, and it was not assessed during this study, as there was no contact with the patients. Second, patients might have made lifestyle changes at any time during therapy that could positively or negatively affect the lipid panel results. Third, lack of a control group regarding lipid values might reflect the fact that the study was conducted during the Thanksgiving and winter holidays. More patients might have been included if the time frame to assess lipid panels had been set at 12 months; before the conversion, patients with well-controlled lipid panels could have a lipid panel drawn every 12 months versus 6 months per the inclusion criteria. Lastly, patient adherence was not assessed, as patients were not contacted during this study. It is unknown why 49% of the initially screened patients did not follow the recommended conversion. Therefore, it cannot be determined whether medication nonadherence might have played a role in the unmet lipid panel goals.
Overall, it can be concluded that with this medication conversion, appropriate follow-up of 6 to 8 weeks—as recommended by the current guidelines1—should be considered to monitor variances in lipid parameters and provide appropriate dosage adjustments so that patients can continue to meet their lipid panel goals. Patients requiring more stringent LDL control were well managed through this conversion, as the majority of T2DM patients remained at goal. Pravastatin was well tolerated during the 24-week period following the conversion.