Examine Additional Statin Titration Studies
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Study Design1: Mean LDL-C percent reduction from untreated baseline following treatment in a multicenter, randomized, double-blind, active controlled, 24-week, forced-titration study (N=788). This study evaluated the efficacy and safety of ZETIA + simvastatin (10/10, 10/20, 10/40, and 10/80 mg) compared with atorvastatin (10, 20, 40, and 80 mg) in reducing LDL-C levels in patients aged ≥18 years with hypercholesterolemia who had not met their NCEP ATP III target LDL-C goal. Patients were randomized equally to atorvastatin 10 mg, ZETIA + simvastatin 10 mg, or ZETIA + simvastatin 20 mg and stratified by baseline LDL-C (mg/dL) ≥130 and <160, ≥160 and <190, and ≥190. Patients were force-titrated every 6 weeks, regardless of goal attainment, up to the 80-mg statin dose. Mean baseline LDL-C for each treatment group: 180.6 mg/dL for atorvastatin 10 mg, 180.0 mg/dL for ZETIA + simvastatin 10 mg, and 179.2 mg/dL for ZETIA + simvastatin 20 mg.
After 6 weeks, mean LDL-C percent reduction from baseline was 37.2% for atorvastatin 10 mg, 46.1% for ZETIA + simvastatin 10 mg, and 50.3% for ZETIA + simvastatin 20 mg (P≤0.05 for both groups treated with ZETIA + simvastatin vs the group treated with atorvastatin 10 mg). Additional LDL-C reduction provided by successive titration of statin in the ZETIA + simvastatin 20-mg arm was 4% (ZETIA + simvastatin 20 mg to ZETIA + simvastatin 40 mg) and 4% (ZETIA + simvastatin 40 mg to ZETIA + simvastatin 80 mg).
Important Information About ZETIA
The effect of ZETIA on cardiovascular morbidity and mortality has not been determined.
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) hyperlipidemia when diet alone is not enough.
Contraindications: hypersensitivity to any component of this medication.
Statin contraindications apply when used with a statin: active liver disease; unexplained persistent elevations in hepatic transaminase levels. 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.
Selected Cautionary Information: When ZETIA was coadministered with a statin, consecutive elevations in hepatic transaminase levels (>3 x 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. Should an increase in ALT or AST >3 x ULN persist, consider withdrawal of ZETIA and/or the statin.
Patients should be advised to promptly report muscle pain, tenderness, or weakness. Risk for skeletal muscle toxicity increases with higher statin doses, advanced age (>65), hypothyroidism, renal impairment, and depending on the statin used, concomitant use of other drugs. Discontinue drug if myopathy is diagnosed or suspected.
ZETIA is not recommended in patients with moderate to severe hepatic impairment.
The coadministration of ZETIA with fibrates other than fenofibrate is not recommended until use in patients is adequately 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, regardless of causality assessment, the most frequent side effects for ZETIA coadministered with a statin vs statin alone included nasopharyngitis (3.7% vs 3.3%), myalgia (3.2% vs 2.7%), upper respiratory tract infection (2.9% vs 2.8%), arthralgia (2.6% vs 2.4%), and diarrhea (2.5% vs 2.2%); for ZETIA administered alone vs placebo: upper respiratory tract infection (4.3% vs 2.5%), diarrhea (4.1% vs 3.7%), arthralgia (3.0% vs 2.2%), sinusitis (2.8% vs 2.2%), and pain in extremity (2.7% vs 2.5%).
Before prescribing ZETIA, please read the Prescribing Information and Patient Product Information.
References: 1. Ballantyne CM, Blazing MA, King TR, Brady WE, Palmisano J. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol. 2004;93:1487–1494.
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