Evolocumab doses of 140mg every 2 weeks (Q2W) or 420mg every month (QM) were associated with greater stability in low-density lipoprotein cholesterol (LDL-C) reduction compared with lower doses of evolocumab, according to findings from a new study published in the Journal of Cardiovascular Pharmacology and Therapeutics

For this study, researchers investigated the pharmacodynamics of evolocumab in two Phase 2 placebo-controlled studies (MENDEL and LAPLACE-TIMI 57) in order to determine which dosing regimens provided the most consistent LDL-C reduction. Patients (N=741) were randomized to receive either 140mg Q2W or 420mg QM, a lower dose (70mg Q2W or 280mg QM) or placebo for 12 weeks. 

Results showed mean reduction in LDL-C for the Q2W visits of 63%, 41.3%, and 1.9% for evolocumab 140mg, 70mg, and placebo, respectively (each P<.001 vs 140mg Q2W), while reductions of 62.7%, 55.5%, and 2.5% were observed for evolocumab 420mg, 280mg, and placebo, respectively with the QM dose (each P<.001 vs 420mg QM).

Peak effect on LDL-C reduction was 72.8% for 140mg Q2W and 69.0% for 420mg QM. An assessment of intrapatient variability indicated a stable effect on LDL-C for both the evolocumab 140mg Q2W and 420mg QM dose (median peak-trough variability of 21%). 

The researchers concluded that “these findings support the initiation of evolocumab at either 140mg Q2W or 420mg QM, depending on patient and prescriber preference, without the need for dose adjustment over time.”

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Evolocumab (Repatha; Amgen)  is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor indicated to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease; as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g, statins, ezetimibe), for treatment of adults with primary hyperlipidemia to reduce LCL-C; and as an adjunct to diet and other LDL-lowering therapies in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C.

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