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| __NOTOC__
| | #REDIRECT [[Fluvastatin]] |
| {{fluvastatin}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Studies==
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| ===Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia===
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| In 12 placebo-controlled studies in patients with primary [[hypercholesterolemia ]]and mixed [[dyslipidemia]], LESCOL was administered to 1621 patients in daily dose regimens of 20 mg, 40 mg, and 80 mg (40 mg twice daily) for at least 6 weeks duration (Table 5). After 24 weeks of treatment, treatment with LESCOL resulted in significantly reduced plasma LDL-C, TC, TG, and Apo B compared to placebo and was associated with variable increases in HDL-C across the dose range.
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| LESCOL XL has been studied in five controlled studies of patients with primary [[hypercholesterolemia]] and mixed [[dyslipidemia]]. LESCOL XL was administered to over 900 patients in trials from 4 to 26 weeks in duration. In the three largest of these studies, LESCOL XL given as a single daily dose of 80 mg significantly reduced Total-C, LDL-C, TG and Apo B and resulted in increases in HDL-C (Table 5).
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| In patients with primary mixed dyslipidemia as defined by baseline plasma TG levels ≥200 mg/dL and <400 mg/dL, treatment with LESCOL/LESCOL XL produced significant decreases in Total-C, LDL-C, TG and Apo B and variable increases in HDL-C (Table 5).
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| |[[File:fluvastatin06.jpg|thumb|800px]]
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| ===Heterozygous Familial Hypercholesterolemia in Pediatric Patients===
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| LESCOL was studied in two open-label, uncontrolled, dose-titration studies. The first study enrolled 29 pre-pubertal boys, 9-12 years of age, who had an LDL-C level >90th percentile for age and one parent with primary [[hypercholesterolemia]] and either a family history of premature ischemic heart disease or tendon xanthomas. The mean baseline LDL-C was 226 mg/dL (range: 137-354 mg/dL). All patients were started on LESCOL capsules 20 mg daily with dose adjustments every 6 weeks to 40 mg daily then 80 mg daily (40 mg b.i.d.) to achieve an LDL-C goal between 96.7 – 123.7 mg/dL. Endpoint analyses were performed at Year 2. LESCOL decreased plasma levels of Total-C and LDL-C by 21% and 27%, respectively. The mean achieved LDL-C was 161 mg/dL (range: 74-336 mg/dL).
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| The second study enrolled 85 male and female patients, 10 to 16 years of age, who had an LDL-C >190 mg/dL or LDL-C >160 mg/dL and one or more risk factors for coronary heart disease, or LDL-C >160 mg/dL and a proven LDL-receptor defect. The mean baseline LDL-C was 225 mg/dL (range: 148-343 mg/dL). All patients were started on LESCOL capsules 20 mg daily with dose adjustments every 6 weeks to 40 mg daily then 80 mg daily (LESCOL 80 mg XL tablet) to achieve an LDL-C goal of <130 mg/dL. Endpoint analyses were performed at Week 114. LESCOL decreased plasma levels of Total-C and LDL-C by 22% and 28%, respectively. The mean achieved LDL-C was 159 mg/dL (range: 90-295 mg/dL).
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| The majority of patients in both studies (83% in the first study and 89% in the second study) were titrated to the maximum daily dose of 80 mg. At study endpoint, 26% to 30% of patients in both studies achieved a targeted LDL-C goal of <130 mg/dL. The long-term efficacy of LESCOL or LESCOL XL therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
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| 14.3 Secondary Prevention of Cardiovascular Disease
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| In the LESCOL Intervention Prevention Study (LIPS), the effect of LESCOL 40 mg administered twice daily on the risk of recurrent cardiac events (time to first occurrence of cardiac death, nonfatal myocardial infarction, or revascularization) was assessed in 1677 patients with CHD who had undergone a [[percutaneous coronary intervention ]]([[PCI]]) procedure (mean time from PCI to randomization=3 days). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with dietary/lifestyle counseling and either LESCOL 40 mg (n=844) or placebo (n=833) given twice daily for a median of 3.9 years. The study population was 84% male, 98% Caucasian, with 37% >65 years of age. Mean baseline lipid concentrations were: total cholesterol 201 mg/dL, LDL-C 132 mg/dL, triglycerides 70 mg/dL and HDL-C 39 mg/dL.
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| LESCOL significantly reduced the risk of recurrent cardiac events (Figure 1) by 22% (p=0.013, 181 patients in the LESCOL group vs. 222 patients in the placebo group). Revascularization procedures comprised the majority of the initial recurrent cardiac events (143 revascularization procedures in the LESCOL group and 171 in the placebo group). Consistent trends in risk reduction were observed in patients >65 years of age.
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| Figure 1 Primary Endpoint – Recurrent Cardiac Events (Cardiac Death, Nonfatal MI or Revascularization Procedure) (ITT Population)
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| Outcome data for the LESCOL Intervention Prevention Study are shown in Figure 2. After exclusion of revascularization procedures ([[CABG]] and repeat [[PCI]]) occurring within the first 6 months of the initial procedure involving the originally instrumental site, treatment with LESCOL was associated with a 32% (p=0.002) reduction in risk of late revascularization procedures ([[CABG]] or [[PCI]] occurring at the original site >6 months after the initial procedure, or at another site).
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| |[[File:fluvastatin08.jpg|thumb|800px]]
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| Figure 2 LESCOL® Intervention Prevention Study - Primary and Secondary Endpoints
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| In the Lipoprotein and Coronary Atherosclerosis Study (LCAS), the effect of LESCOL therapy on coronary [[atherosclerosis ]]was assessed by quantitative coronary angiography (QCA) in patients with CAD and mild to moderate [[hypercholesterolemia]] (baseline LDL-C range 115-190 mg/dL). In this randomized double-blind, placebo- controlled trial, 429 patients were treated with conventional measures (Step 1 AHA Diet) and either LESCOL 40 mg/day or placebo. In order to provide treatment to patients receiving placebo with LDL-C levels ≥160 mg/dL at baseline, adjunctive therapy with cholestyramine was added after Week 12 to all patients in the study with baseline LDL-C values of ≥160 mg/dL which were present in 25% of the study population. Quantitative coronary angiograms were evaluated at baseline and 2.5 years in 340 (79%) angiographic evaluable patients.
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| Compared to placebo, LESCOL significantly slowed the progression of coronary atherosclerosis as measured by within-patient per-lesion change in minimum lumen diameter (MLD), the primary endpoint (Figure 3 below), percent diameter stenosis (Figure 4), and the formation of new lesions (13% of all fluvastatin patients versus 22% of all placebo patients). A significant difference in favor of LESCOL was found between all fluvastatin and all placebo patients in the distribution among the three categories of definite progression, definite regression, and mixed or no change. Beneficial angiographic results (change in MLD) were independent of patients’ gender and consistent across a range of baseline LDL-C levels.
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| |[[File:fluvastatin09.jpg|thumb|800px]]
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| {|
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| |[[File:fluvastatin10.jpg|thumb|800px]]
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| <ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = LESCOL (FLUVASTATIN SODIUM) CAPSULE LESCOL XL (FLUVASTATIN SODIUM) TABLET, EXTENDED RELEASE [NOVARTIS PHARMACEUTICALS CORPORATION] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8a1823e7-26fb-4858-bac7-9e152e5ea16a | publisher = | date = | accessdate = 12 February 2014 }}</ref>
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| ==References==
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| {{Reflist|2}}
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| {{Statins}}
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| [[Category:Statins]]
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| [[Category:Diols]]
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| [[Category:Indoles]]
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| [[Category:Carboxylic acids]]
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| [[Category:Organofluorides]]
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| [[Cardiovasular Druf]]
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| [[Drug]]
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