Adverse events to PCSK-9 inhibitors: what is the current evidence?

There is a train of thought that lipid therapies may delay or limit the impact of neuronal loss and poor patient outcomes of neurodegenerative diseases (NDDs). A variety of medicines including lipid lowering modifiers (LLMs) are prescribed in NDDs. This paper summarizes the findings of clinical and observational trials including systematic reviews and meta-analyses relating to LLM use in NDDs published in the last 15 years thus providing an up-to-date evidence pool. Three databases were searched PubMed, CINAHL, and Web of Science using key terms relating to the review question. The findings confirm the benefit of LLMs in hyperlipidemic patients with or without cardiovascular risk factors due to their pleotropic effects. In NDDs LLMs are proposed to delay disease onset and slow the rate of progression. Clinical observations show that LLMs protect neurons from α-synuclein, tau, and Aβ toxicity, activation of inflammatory processes, and ultimately oxidative injury. Moreover, current meta-analyses and clinical trials indicated low rates of adverse events with LLMs when used as monotherapy. LLMs appear to have favorable safety and tolerability profiles with few patients stopping treatment due to severe adverse effects. Our collated evidence thus concludes that LLMs have a role in NDDs but further work is needed to understand the exact mechanism of action and reach more robust conclusions on where and when it is appropriate to use LLMs in NDDs in the clinic.

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A review on the efficacy and safety of lipid-lowering drugs in neurodegenerative disease

Rajabian

McCloskey

Jamialahmadi

et al. 2023

Reviews in the Neurosciences

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Post liver transplant refractory dyslipidemia

Thulasidass,

Varghese,

Premkumar

2024

IJEM Case Rep

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A 53-year-old male presented with intractable pruritus and jaundice. He underwent liver transplantation for liver cirrhosis a year prior to the current presentation. Post-transplantation, he developed diabetes mellitus. He experienced an episode of early acute graft rejection, 2 months after transplantation, which was successfully treated. Subsequently, about a year after transplantation, he developed chronic graft rejection. He was treated with everolimus and prednisolone. Incidentally, he was found to have elevated blood cholesterol, triglycerides, and low density lipoprotein (LDL) levels. The lipid levels were significantly higher than those commonly encountered in post-liver transplant patients. Dyslipidemia was treated with maximum dose of high-intensity statin, ezetimibe, and fenofibrate. However, there was not much reduction in lipid levels, indicating resistance to treatment. Subsequently, injection evolocumab 140 mg subcutaneously was added, administered once every 2 weeks. Following that, after only three doses of injection, there was about 65% reduction in the LDL level, which sustained at lower levels with continued treatment using evolocumab. Evolocumab was proven to be highly effective in reducing lipid levels in post-liver transplant patients who are refractory to treatment with conventional lipid-reducing medications.

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Adverse events to PCSK-9 inhibitors: what is the current evidence?

Cited by 2 publications

References 22 publications

A review on the efficacy and safety of lipid-lowering drugs in neurodegenerative disease

A review on the efficacy and safety of lipid-lowering drugs in neurodegenerative disease

Post liver transplant refractory dyslipidemia

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