Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials

Abstract

AimsThis analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.Materials and MethodsData from 4983 randomized patients (1940 with MetS; 1642 with diabetes excluded) were assessed in subgroups by MetS status. Efficacy data were analysed in 4 pools per study design: 2 placebo‐controlled pools (1 using alirocumab 150 mg every 2 weeks [Q2W], 1 using 75/150 mg Q2W) with background statin, and 2 ezetimibe‐controlled pools (both alirocumab 75/150 mg Q2W), 1 with and 1 without background statin. Alirocumab 75/150 mg indicates possible dose increase from 75 to 150 mg at Week 12 based on Week 8 LDL‐C.ResultsLDL‐C percentage reduction from baseline at Week 24 with alirocumab was 63.9% (MetS) and 56.8% (non‐MetS) in the pool of alirocumab 150 mg Q2W, and 42.2% to 52.2% (MetS) and 45.0% to 52.6% (non‐MetS) in 3 pools using 75/150 mg Q2W. Levels of other lipid and lipoprotein parameters were also improved with alirocumab treatment, including apolipoprotein B, non‐high‐density lipoprotein cholesterol (non‐HDL‐C), lipoprotein(a) and HDL‐C. Overall, the percentage change at Week 24 in LDL‐C and other lipids and lipoproteins did not vary by MetS status. Adverse event rates were generally similar between treatment groups, regardless of MetS status; injection‐site reactions occurred more frequently in alirocumab vs control groups.ConclusionsAcross study pools, alirocumab‐associated reductions in LDL‐C, apolipoprotein B, and non‐HDL‐C were significant vs control, and did not vary by MetS status.

Effects of Alirocumab on Triglyceride Metabolism: A Fat-Tolerance Test and Nuclear Magnetic Resonance Spectroscopy Study

“…We could only detect a modest, non-significant reduction in fasting plasma triglycerides of 10%. This result is consistent with findings of a large, pooled analysis of 10 phase III alirocumab trials with 4983 participants, also reporting a modest triglyceride reduction of approximately 15% [ 33 ]. The pooled analysis also suggested that the triglyceride-lowering effect of alirocumab treatment is independent of a metabolic syndrome.…”

Proteinuria converts hepatic heparan sulfate to an effective proprotein convertase subtilisin kexin type 9 enzyme binding partner

“…68 Targeting PCSK9 has emerged as a novel approach to treat hypercholesterolemia. [69][70][71][72][73] Other potential novel therapies are heparin mimetics. Heparin and related compounds are known to lower plasma TG concentrations by releasing lipoprotein lipase into plasma.…”

PCSK9 inhibitors and diabetes: Translational biology to clinical practice

“…Henry et al found a significant reduction in apolipoprotein B (40%‐50% reduction with statins) and similar reductions on non‐HDLs with PCSK9 inhibitors. There were no significant differences between patients with or without metabolic syndrome …”

“…There were no significant differences between patients with or without metabolic syndrome. 4 In summary, the use of PCSK9 inhibitors in patients with cardiometabolic conditions has impressive benefits. In intolerant statins, patients frequently benefit from these compounds, but the cost is high.…”