Abstract

• The cholesterol-lowering drugs of first choice for adults with hypercholesterolaemia are pravastatin and simvastatin. Colestyramine and gemfibrozil are other options.
   
• In patients with homozygous familial hypercholesterolaemia, cholesterol-lowering drugs, even when used at high doses, seldom eliminate the need for LDL lipoprotein apheresis, a burdensome and inconvenient procedure.
   
• Evolocumab is the first monoclonal antibody targeting PCSK9, an enzyme involved in regulating hepatic LDL cholesterol receptors, to be authorised in the European Union.
   
• Clinical evaluation of evolocumab includes about ten trials, mainly conducted in patients with no history of cardiovascular events. These trials generally lasted only a few months and used surrogate lipid endpoints. Thus, in early 2016, there is no evidence that evolocumab is effective in reducing morbidity or mortality.
   
• In patients with hypercholesterolaemia, the five principal randomised controlled trials showed that evolocumab, alone or in combination with other cholesterol-lowering drugs, reduced LDL-cholesterol levels by about 55% to 75% versus placebo after 12 weeks of treatment and at one year.
   
• Two trials including a total of 145 patients with homozygous familial hypercholesterolaemia showed that evolocumab reduced LDL-cholesterol by between 17% and 30% after 12 weeks of treatment, but its impact on the frequency of apheresis sessions was not reported.
   
• Evolocumab provokes injection site reactions, infections, hypersensitivity reactions and, possibly, muscle damage. Long-term harms are poorly documented and must therefore be a focus of post-marketing surveillance.
   
• In practice, in early 2016, evolocumab has only been shown to provide a marked reduction in LDL cholesterol levels. Its efficacy is unknown, and its long-term adverse effects are poorly documented. It is more prudent to use better assessed drugs, pending the results of ongoing trials.

©Prescrire 1 September 2016

"Evolocumab (Repatha°). A "mab" for hypercholesterolaemia: no evidence of benefits" Prescrire Int 2016; 25 (174): 201-205. (Pdf, subscribers only)