Physicians' Academy for Cardiovascular Education

Long-term PCSK9 inhibitor safe and effective in HeFH

Long-term Safety, Tolerability, and Efficacy of Evolocumab in Patients With Heterozygous Familial Hypercholesterolemia

Literature - Hovingh GK, Raal FJ, Dent R, et al. - J Clin Lipidol (2017), doi: 10.1016/j.jacl.2017.09.003


Patients with heterozygous familial hypercholesterolemia (HeFH) have increased plasma low-density lipoprotein cholesterol (LDL-C) levels, mainly due to genetic mutations in the LDL receptor gene [1], resulting in an increased cardiovascular (CV) risk. Of the estimated 34 million patients [2,3] worldwide, a large portion is not treated. Another part uses lipid lowering agents, such as statins, which do not result in sufficient reduction of LDL-C levels. Therefore, there is an unmet need for additional therapies to reduce the residual CV risk in this patient population.

Although it has been demonstrated that the PCSK9 antibody evolocumab safely lowered LDL-C levels in HeFH patients in phase II and III RUTHERFORD trials [4,5], long-term effects are not known yet. These long-term effects were evaluated in the evolocumab open-label extension (OLE) trial program (OSLER-1 and OSLER-2).

After completion of the RUTHERFORD trial, patients were enrolled in the OLE program and re-randomized 2:1 to receive evolocumab in addition to standard of care (SOC) or SOC alone for 48 weeks. Of the 440 enrolled patients, 289 were enrolled in the evolocumab plus SOC group and 151 in the SOC alone group.

Main results


This open-label extension trial of evolocumab demonstrated that long-term use (48 weeks) of this PCSK9 inhibitor in combination with SOC reduced the levels of LDL-C and was well tolerated in a HeFH patient population of , who need additional therapy to reduce their CV risk.


Show references

Find this article online at Lipid Journal

Share this page with your colleagues and friends: