Statin-associated Muscle Symptoms: Impact on Statin Therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

Erik S. Stroes; Paul D. Thompson; Alberto Corsini; Georgirene D. Vladutiu; Frederick J. Raal; Kausik K. Ray; Michael Roden; Evan Stein; Lale Tokgözoğlu; Børge G. Nordestgaard; Eric Bruckert; Guy De Backer; Ronald M. Krauss; Ulrich Laufs; Raul D. Santos; Robert A. Hegele; G. Kees Hovingh; Lawrence A. Leiter; Francois Mach; Winfried März; Connie B. Newman; Olov Wiklund; Terry A. Jacobson; Alberico L. Catapano; M. John Chapman; Henry N. Ginsberg


Eur Heart J. 2015;36(17):1012-1022. 

In This Article

Future Low-density Lipoprotein-lowering Therapies for Patients With Statin-associated Muscle Symptoms

Two classes of novel therapies, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and cholesteryl ester transfer protein (CETP) inhibitors, offer potential as alternatives for the management of patients with persistent SAMS.

PSCK9 Inhibitors

PCSK9 is a circulating protein that binds to the LDL receptor and targets it for degradation.[63] First identified in 2003 and shown to be related to autosomal-dominant hypercholesterolaemia, PCSK9 has become a therapeutic target for potently reducing LDL-C in humans.[64,65] Clinical development of human monoclonal antibodies has progressed very rapidly, with the most advanced being evolocumab, alirocumab, and bococizumab. Studies have consistently shown large LDL-C reductions of 50–60% in a variety of patient groups,[64,65] including those identified as statin intolerant,[66–68] with a very low rate of muscle symptoms, thus reinforcing the concept that statin rather than LDL-C lowering is implicated in the causation of myopathy. In clinical trials including over 6000 patients treated for 3 to 12 months, the tolerability of these subcutaneously administered drugs has been very good, with few injection site reactions and no significant liver function abnormalities or CK elevations.[69,70] Four large CVD outcomes trials are ongoing and initial results are anticipated in 2017.[71–74]

Cholesteryl Ester Transfer Protein Inhibitors

Cholesteryl ester transfer protein mediates the heteroexchange of triglycerides and cholesteryl esters between lipoproteins. Inhibitors of CETP can markedly increase high-density lipoprotein cholesterol, and two members of this class in advanced development, anacetrapib and evacetrapib, equally lower LDL-C by 25–40%.[75,76] The mechanism for LDL-C lowering involves increased fractional removal rates for LDL apolipoprotein B from plasma although the molecular basis for this is unclear. Importantly, no side effects involving the musculoskeletal system have been identified with CETP inhibitors. Two large clinical trials to determine whether anacetrapib or evacetrapib reduce CVD events in high-risk patients are underway.[77,78]