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Genetic findings reported approximately 9 years ago in the Journal indicated that rare sequence variants in the gene encoding proprotein convertase subtilisin–kexin type 9 serine protease (PCSK9) were associated with significantly lower long-term plasma levels of low-density lipoprotein (LDL) cholesterol.1 The observed reduction in LDL cholesterol levels was similar to that attained with moderate-intensity statin therapy. The benefits of lifelong lowering of LDL cholesterol levels were substantial; a 47 to 88% lower risk of coronary heart disease was observed over a period of 15 years in middle-aged persons with such genetic polymorphisms. Further genetic studies indicated that PCSK9 activity was a major determinant of plasma levels of LDL cholesterol in humans.2
Two reports now published in the Journal describe the results of long-term studies of treatment with monoclonal antibodies to PCSK9 to lower LDL cholesterol levels. One trial, entitled Long-Term Safety and Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM), was a double-blind, randomized, controlled trial of alirocumab (150 mg administered subcutaneously every 2 weeks) versus placebo for 78 weeks in 2341 patients at high risk for cardiovascular events who were already receiving the maximum tolerated doses of statins.3 Two other trials, entitled Open-Label Study of Long-Term Evaluation against LDL Cholesterol 1 (OSLER-1) and OSLER-2, used a randomized,...