Examine Additional Statin Titration Studies
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Study Design4: A 36-week, randomized, double-blind, parallel-group, dose-titration study in patients with hypercholesterolemia (N=826) with LDL-C >160 mg/dL and triglycerides <350 mg/dL randomized to receive either simvastatin 40 mg titrated to 80 mg at 6 weeks or atorvastatin 20 mg titrated every 6 weeks up to 80 mg. The primary end point was change from baseline in HDL-C averaged across the 2 dose comparisons in the initial 12 weeks. Mean baseline HDL-C and LDL-C levels were 50 mg/dL and 209 mg/dL for the simvastatin group and 51 mg/dL and 206 mg/dL for the atorvastatin group, respectively. Across Weeks 6 and 12, mean change from baseline in HDL-C was 9% with simvastatin vs 7% with atorvastatin (P<0.001).
After 6 weeks, mean LDL-C reduction from baseline was 46% with atorvastatin 20 mg vs 42% with simvastatin 40 mg (P≤0.001). After 12 weeks, mean LDL-C reduction from baseline was 51% with atorvastatin 40 mg vs 49% with simvastatin 80 mg (P≤0.001). After Weeks 18 to 36, mean LDL-C reduction from baseline was 54% with atorvastatin 80 mg vs 48% with simvastatin 80 mg (P≤0.001).
Additional LDL-C reduction provided by titration of atorvastatin 20 mg to 40 mg was 5% and from atorvastatin 40 mg to 80 mg was 3%. Additional LDL-C reduction provided by titration of simvastatin 40 mg to 80 mg was 6%.
The additional percent reductions in LDL-C with successive doses were obtained by subtraction from data presented.
Important Information About ZETIA
ZETIA, administered alone or in combination with an HMG-CoA reductase inhibitor (statin), is indicated as adjunctive therapy to diet for the reduction of elevated TOTAL-C, LDL-C, and Apo B in patients with primary (heterozygous familial and nonfamilial) hypercholesterolemia when diet alone is not enough.
Contraindications: hypersensitivity to any component of this medication.
Contraindications when used with a statin: active liver disease; unexplained persistent elevations of serum transaminases. Statins are contraindicated in pregnant and nursing women; refer to the statin label for details.
When using ZETIA with a statin, also follow the label recommendations for that specific statin.
The effects of ZETIA, either alone or in addition to a statin, on the risk of cardiovascular morbidity and mortality have not been established.
Selected Cautionary Information: When ZETIA was coadministered with a statin, consecutive elevations in serum transaminases (≥3 × ULN) were slightly higher (1.3%) than those of statins alone (0.4%). Liver function tests should be performed when ZETIA is added to statin therapy and according to statin recommendations.
Patients should be advised to promptly report muscle pain, tenderness, or weakness. Discontinue drug if myopathy is diagnosed or suspected.
ZETIA is not recommended in patients with moderate or severe hepatic insufficiency.
The coadministration of ZETIA with fibrates other than fenofibrate is not recommended until use in patients is studied.
Exercise caution when using ZETIA and cyclosporine concomitantly because exposure to both drugs is increased. Cyclosporine concentrations should be monitored in these patients.
ZETIA should be used in pregnant or nursing women only if the benefit outweighs the risk.
In clinical trials, the most frequent side effects for ZETIA alone vs placebo included back pain (4.1% vs 3.9%), arthralgia (3.8% vs 3.4%), and fatigue (2.2% vs 1.8%); for ZETIA + statin vs statin or placebo alone: back pain (4.3% vs 3.7% vs 3.5%), abdominal pain (3.5% vs 3.1% vs 2.3%), and fatigue (2.8% vs 1.4% vs 1.9%).
Before prescribing ZETIA, please read the Prescribing Information and Patient Product Information.
Reference: 4. Illingworth DR, Crouse JR III, Hunninghake DB, et al, and the Simvastatin Atorvastatin HDL Study Group. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr Med Res Opin. 2001;17:43–50.
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