Majority of hypercholesterolaemia patients reaches target LDL-c with evolocumab
LDL-C Assessment w/ PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2 (LAPLACE-2)
BackgroundDespite the efficacy of statins, their effect are not sufficient for all patients. Many patients do not achieve target levels for LDL-c with high doses of statins, and need other LDL-lowering medication. Evolocumab (AMG 145) is a human antibody against PCSK9. In phase 2 studies evolocumab was well tolerated and showed robust LDL-c reductions.
In this randomised, multicenter study the tolerability and efficacy with respect to LDL-c of evolocumab was evaluated, in comparison to both placebo and ezetimibe, in hypercholesterolaemic participants on statins. The primary endpoint was percent change in LDL-c levels from baseline, after 12 weeks of treatment with a biweekly (140 mg, Q2W) of monthly (420 mg, Q4W) subcutaneous dose of evolocumab in addition to statin treatment, relative to placebo or ezetimibe.
- The mean reduction of LDL-c after 10 and 12 weeks was 63-75% with evolocumab (Q2W and Q4W), in comparison to placebo, while ezetimibe gave a reduction of 19-32% relative to placebo. This was seen in combination with more or less intensive statin regimes.
- In contrast to in the other treatment regimes, treatment with evolocumab caused the majority of patients to achieve target LDL-c (<70 mg/dL), both in Q2W and Q4W (86-94% with moderately intense and 93-95% with intense statin treatment).
- Strong reductions were also seen with evolocumab in non-HDL cholesterol (-58-65%) and ApoB (-51-59%) (Q2W and Q4W), irrespective of statin regime. Reductions with ezetimibe were around 20% and 30% for non-HDL-c and ApoB respectively.
- Lipoprotein(a) diminished with 21-36% on evolocumab (Q2W and Q4W, irrespective of statin regime), while other treatments did not show reductions.
- Evolocumab was tolerated at least as well as the statin and ezetimibe treatments.