In patients with primary mixed dyslipidemia (Fredrickson Type IIb) as defined by baseline plasma triglycerides levels ≥ 200 mg/dL, Lescol XL 80 mg produced a median reduction in triglycerides of 25%. In these patients, Lescol XL 80 mg produced median (25th and 75th percentile) percent change from baseline in HDL-C of +11(+3,+20). Significant decreases in Total-C, LDL-C, and Apo B were also achieved. In these studies, patients with triglycerides > 400 mg/dL were excluded.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients

Fluvastatin sodium was studied in two open-label, uncontrolled, dose-titration studies which enrolled pediatric patients with heterozygous familial hypercholesterolemia. 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 bid) to achieve an LDL-C goal of 96.7 to 123.7 mg/dL. Endpoint analyses were performed at Year 2. 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.

In the first study, Lescol 20 mg to 80 mg daily doses 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). In the second study, Lescol 20 mg to 80 mg daily doses 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).

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.

Reduction in the Risk of Recurrent Cardiac Events

In the Lescol Intervention Prevention Study, 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 coronary heart disease 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. At baseline patients had total cholesterol between 100 and 367 mg/dL (mean 201 mg/dL), LDL-C between 42 and 243 mg/dL (mean 132 mg/dL), triglycerides between 15 and 270 mg/dL (mean 70 mg/dL) and HDL-C between 8 and 174 mg/dL (mean 39 mg/dL).

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.

Figure 1. Primary Endpoint - Recurrent Cardiac Events (Cardiac Death,Nonfatal MI or Revascularization Procedure) (ITT Population)

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).

Figure 2. Lescol® Intervention Prevention Study - Primary and SecondaryEndpoints

Atherosclerosis

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