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LAPLACE-TIMI 57

Posted on 30 July 2020 | Posted in Evolocumab
Trial LAPLACE-TIMI 57 (LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition combined with statin therapy- Thrombolysis in Myocardial Infarction) trial.
Aim To assess the efficacy, safety, and tolerability of evolocumab in stable patients with hypercholesterolaemia on a statin.
Study design Multicentre, randomised, double-blind placebo-controlled, parallel group study. (Phase II dose-ranging study).
Patient population Patients (aged 18-80 years) at 78 centres in the USA, Canada, Denmark, Hungary, and Czech Republic, with LDL-C >2·2 mmol/L (85 mg/dL) on a stable dose of atorvastatin (with or without ezetimibe) for at least 4 weeks.Patients (n=631) were randomly assigned to groups receiving doses of evolocumab, every 2 weeks (70 mg [n=79], 105 mg [n=79], 140 mg [n=78] vs placebo [n=78]) or very 4 weeks (280 mg [n=79], 350 mg [n=79], 420 mg [n=80] vs placebo [n=79]), compared with placebo.
Primary efficacy endpoint Percentage change in LDL-C concentration from baseline after 12 weeks on study treatment.
Other endpoints
  • Absolute change from baseline to 12 weeks in LDL-C.
  • Percentage change from baseline to 12 weeks in non-HDL-C, apo B and A-I, and the ratios of TC/HDL-C and apoB/A-I.
Key results Efficacy: At the end of the dosing interval at week 12, the mean LDL-C concentrations were reduced generally dose dependently by evolocumab every 2 weeks (ranging from 41·8% to 66·1%; p<0·0001 for each dose vs placebo) and evolocumab every 4 weeks (ranging from 41·8% to 50·3%; p<0·0001).There were significant reductions from baseline at week 12 versus placebo for the absolute change in LDL-C and the percentage change in non-HDL-C and apoB, and ratios of TC/HDL-C and apoB/apoA-I (p<0·0001 for each dose vs placebo).

Safety: The most common adverse events were nasopharyngitis (10% with evolocumab vs 7% with placebo), cough (3% vs 2%], nausea (3% vs 0·6%) and injection site reactions (2% in each group). No patients developed anti-evolocumab antibodies, neutropenia, or vasculitis.

No treatment-related serious adverse events occurred. The frequencies of treatment-related adverse events were similar in the evolocumab and placebo groups (39 [8%] of 474 vs 11 [7%] of 155); none of these events were severe or life-threatening.

Author conclusion The results suggest that PCSK9 inhibition could be a new model in lipid management. Inhibition of PCSK9 warrants assessment in phase 3 clinical trials.
Link Giugliano RP, Desai NR, Kohli P, et al. Lancet 2012;380(9858):2007-17.http://www.ncbi.nlm.nih.gov/pubmed/23141813

ClinicalTrials.gov number NCT01380730

 

Trial LAPLACE-TIMI 57 (LDL-C Assessment with Proprotein Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition combined with statin therapy- Thrombolysis in Myocardial Infarction) trial.
Aim To evaluate the impact of evolocumab on lipoprotein(a) [Lp(a)].
Study design Multicentre, randomised, double-blind placebo-controlled, parallel group study. (Phase II dose-ranging study).
Patient population 631 patients with hypercholesterolaemia receiving statin therapy were randomised to receive evolocumab at 1 of 3 different doses every 2 weeks or 1 of 3 different doses every 4 weeks versus placebo. (Doses as in Giugliano RP et al. 2012, above).
Primary efficacy endpoint Percentage change in Lp(a) concentration from baseline after 12 weeks on study treatment.
Key results Efficacy:Compared with placebo, evolocumab reduced Lp(a) as follows:

Evolocumab dose Reduction in Lp(a) at 12 weeks
70 mg every 2 weeks -18%, p<0.001 vs placebo
105 mg every 2 weeks -32%, p<0.001 vs placebo
140 mg every 2 weeks -32%, p<0.001 vs placebo
280 mg every 4 weeks -18%, p<0.001 vs placebo
350 mg every 4 weeks -23%, p<0.001 vs placebo
420 mg every 4 weeks -23%, p<0.001 vs placebo
  • The reduction in Lp(a) correlated with the reduction in low-density lipoprotein cholesterol.
  • The effect of evolocumab on Lp(a) was consistent regardless of age, sex, race, history of diabetes mellitus, and background statin regimen.
  • Patients with higher levels of Lp(a) at baseline had larger absolute reductions but comparatively smaller percent reductions in Lp(a) with evolocumab compared with those with lower baseline Lp(a) values.
Author conclusion Evolocumab significantly reduces Lp(a), by up to 32%, among subjects with hypercholesterolaemia receiving statin therapy, offering an additional, complementary benefit beyond robust LDL-C reduction with regard to a patient's atherogenic lipid profile.
Link Desai NR, Kohli P, Giugliano RP, et al. Circulation 2013; 128(9): 962-9.http://www.ncbi.nlm.nih.gov/pubmed/23884353

ClinicalTrials.gov number NCT01380730

 

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