HMG-CoA Reductase Inhibitor ("Statin") Interchange to Simvastatin
Emily Chan, B.Sc. (Pharm), Rubina Sunderji, Pharm.D., Karen
Why lower blood cholesterol?
Lipid lowering therapy with statins has been shown to decrease mortality in patients with and without coronary artery disease (CAD). Specifically, simvastatin 20-40mg daily significantly reduced mortality in a secondary prevention trial (8.2% vs 11.5% placebo).1 Pravastatin 40mg daily has signficantly reduced mortality when used for secondary prevention (11.0% vs 14.1% placebo)2 and primary prevention (3.2% vs 4.1% placebo)3.
What are the goals for cholesterol lowering?
The Canadian Working Group on High Cholesterol has published guidelines for the treatment of elevated cholesterol levels based on an individuals risk factors for CAD.4 Table 2 illustrates the treatment goals based on the number of risk factors and LDL concentration.
|# Risk Factors||Target LDL (mmol/L)|
|One or less||< 5.0|
|Four or more or CAD||< 2.5|
Risk factors: age (male > 45 y,
female > 55 y or
post- menopausal not on hormone replacement therapy),
diabetes, family history of premature CAD (male < 55 y, female < 65 y),
smoking, hypertension, left ventricular hypertrophy
Table 2. Target LDL
Choice of Formulary Statin
Lovastatin is the current formulary statin at VHHSC. Table 3 illustrates the approximate equivalent dose and cost of the 6 statin agents available in Canada. All statins cause a similar reduction in LDL levels at comparable doses. The only trials published to date that have shown reductions in overall mortality have been conducted with simvastatin and pravastatin. While atorvastatin has been purported to cause the greatest reduction in triglyceride levels (19-37% vs 10-15% with other statins)5, a recent head-head trial showed no difference between atorvastatin, simvastatin, pravastatin, fluvastatin, or lovastatin on triglyceride lowering effects at usual doses6.
Simvastatin has been chosen as the statin drug for the VHHSC formulary based on the following: a) scientific evidence for survival benefit, and b) similar or lower cost (at higher doses) compared to lovastatin.
|Drug||Approximate Equivalent Dose||Cost/30 days|
Dose equivalence based on a 25-30% reduction in LDL cholesterol
Costs based on VHHSC acquisition costs
Table 3. Comparison of statin drugs
Therapeutic Interchange of Statins to Simvastatin
Due to the number of alternative statin drugs, a therapeutic interchange policy will be implemented on January 11, 1999. Thereafter, all inpatient prescriptions for statin drugs will be converted to simvastatin at the equivalent dosage as listed in table 3. "Do not substitute" may be written for an individual statin prescription if the patient has brought their own supply into the hospital.
4S Study Group. Lancet 1994;344:1383-9.
LIPID Study Group. N Engl J Med 1998;339:1349-57.
WOSCOP Study Group. N Engl J Med 1995;333:1301-7.
Working Group on Hypercholesterolemia. Can J Cardiol 1998;14(Suppl A):17A-21A.
Chong PH et al. Pharmacother 1997;17:1157-77.
Nawrocki JW et al.Aterioscler Thromb Vasc Biol 1995;15:678-82.