Atorvastatin With or Without an Antibody to PCSK9 in Primary Hypercholesterolemia
What are the effects of SAR236553 coadministered with high-dose or low-dose atorvastatin, as compared with high-dose atorvastatin alone, in patients with low-density lipoprotein (LDL) cholesterol levels of 100 mg/dl or higher?
The investigators performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg/dl (2.6 mmol/L) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks, and were followed for an additional 8 weeks after treatment.
The least-squares mean (± standard error) percent reduction from baseline in LDL cholesterol was 73.2 ± 3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3 ± 3.5 with 80 mg of atorvastatin plus placebo (p < 0.001) and 66.2 ± 3.5 with 10 mg of atorvastatin plus SAR236553. All the patients who received SAR236553, as compared with 52% of those who received 80 mg of atorvastatin plus placebo, attained an LDL cholesterol level of <100 mg/dl, and at least 90% of the patients who received SAR236553, as compared with 17% who received 80 mg of atorvastatin plus placebo, attained LDL cholesterol levels of <70 mg/dl (1.8 mmol/L).
The authors concluded that in patients with primary hypercholesterolemia, adding SAR236553 to either atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with atorvastatin alone.
This phase 2 trial suggests that the combination of 80 mg of atorvastatin plus SAR236553 (fully human PCSK9 monoclonal antibody) resulted in significantly greater reductions in LDL cholesterol levels than did 80 mg of atorvastatin alone. Furthermore, substantially more patients who received SAR236553 than patients who received placebo attained target LDL cholesterol levels of <100 mg/dl and <70 mg/dl. Since this was a small study of short duration, additional larger studies with longer-term follow-up and hard clinical efficacy and safety endpoints are indicated.
Keywords: Pyrroles, Cholesterol, Follow-Up Studies, Cardiology, Cardiovascular Diseases, Lipoproteins, Heptanoic Acids, Hypercholesterolemia
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