Atorvastatin with or without an antibody to PCSK9 in primary
hypercholesterolemia.
Author(s): Roth EM, McKenney JM, Hanotin C, Asset G, Stein EA.
Affiliation(s): Sterling Research Group, Cincinnati, OH, USA.
Publication date & source: 2012, N Engl J Med. , 367(20):1891-900
BACKGROUND: Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to
low-density lipoprotein (LDL) receptors, increasing the degradation of LDL
receptors and reducing the rate at which LDL cholesterol is removed from the
circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human
PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces
LDL cholesterol levels.
METHODS: We performed a phase 2, multicenter, double-blind, placebo-controlled
trial involving 92 patients who had LDL cholesterol levels of 100 mg per
deciliter (2.6 mmol per liter) 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.
RESULTS: The least-squares mean (±SE) 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 less than 100 mg per deciliter, 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 less than 70
mg per deciliter (1.8 mmol per liter).
CONCLUSIONS: In a randomized trial involving patients with primary
hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg
of atorvastatin resulted in a significantly greater reduction in LDL cholesterol
than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and
Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.).
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