Abstract 1636: Efficacy and Safety of Combination Torcetrapib/Atorvastatin versus Atorvastatin Alone in Patients with Heterozygous Familial Hypercholesterolemia
Background: Patients with heterozygous familial hypercholesterolemia (HeFH) have a primary defect in the LDL receptor gene and are characterized by marked elevations in LDL-C and an increased risk of premature cardiovascular disease. Statin therapy has been demonstrated to lower LDL-C levels in HeFH subjects. Torcetrapib (T) is a cholesteryl ester transfer protein (CETP) inhibitor that has been shown to raise HDL-C and lower LDL-C when administered concomitantly with atorvastatin (A) in subjects without overt cardiovascular disease. This phase 3 study assessed the lipid efficacy and safety of combination T/A versus A alone in subjects with HeFH.
Study Design: In this multi-center, double-blind trial, 437 subjects were treated for 4–16 weeks with A (20, 40 or 80 mg/day) titrated to attain an LDL-C level according to NCEP ATP III criteria or the maximally tolerated dose. Subjects were then randomized to 24 weeks of treatment with combination T/A or A alone at doses of T 60 mg combined with A at the dose reached at the end of the titration period.
Results: Baseline characteristics were well matched between treatment groups. Combination T/A and A alone produced mean HDL-C elevations from baseline of +57.67% and +1.00%, respectively; a between-group difference of +56.68% (P<0.0001). T/A and A alone changed LDL-C levels from baseline by −18.37% and +8.75%, respectively; a between-group difference of −27.12% (P<0.0001). For T/A and A, the drug-related discontinuation rates due to adverse events were 6.3% and 2.8%, respectively. There was no evidence of increased rates of liver enzyme elevation or muscle-related adverse events. T/A showed a 2.01 mmHg (95% CI, −0.14, 4.15) increase in systolic BP from baseline, when compared to A alone.
Conclusions: In HeFH patients, combination T/A produced substantial elevations in HDL-C and additional marked reductions in LDL-C when compared to A alone. T/A was well tolerated in HeFH patients.