Muscle-Related Adverse Events Associated With PCSK9 Inhibitors in a Veteran Population

Cencetti, Joseph

doi:10.12788/fp.0357

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Unfortunateley, this hypothesis does not seem valid for muscle disorders induced by PCSK9 inhibitors or ezetimibe, since they do not deplete ubiquinone. Furthermore, it has been observed that muscle disorders induced by PCSK9 inhibitors are evident later in the treatment, with respect to statins [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Adverse Reactions to Evolocumab: Analysis of Real-World Data from EudraVigilance

Calapai,

Mannucci,

Currò

et al. 2024

Pharmaceuticals

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Background: Evolocumab is a humanized immunoglobulin G2 monoclonal antibody, directed against Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9), prescribed in hypercholesterolemic patients. The safety profile of this drug is currently defined by the data of pre-authorization clinical trials. The purpose of this study is to update knowledge of the safety of evolocumab through an analysis of post-marketing real-world data on suspected adverse reactions (SARs), reported by the EudraVigilance database system. Methods: The public version of the EudraVigilance database has been used, and only serious SARs signals were included. Results: Musculoskeletal system disorders, flu-like symptoms, injection-site reactions, skin reactions, and metabolism and nutrition disorders are observed in the post-marketing surveillance, as well as being found in the pre-authorization studies. Not previously signaled in the pre-marketing studies, diarrhea was reported. Furthermore, signals related to cardiac adverse reactions, more frequently at the expense of adults in comparison to elders, were found. Conclusions: The post-marketing safety profile of evolocumab emerging from an analysis of the EudraVigilance data system indicates it is sufficiently safe but suggests the necessity for caution when it is prescribed to hyperlipidemic patients affected by heart diseases.

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Section: Discussionmentioning

confidence: 99%

Adverse Reactions to Evolocumab: Analysis of Real-World Data from EudraVigilance

Calapai,

Mannucci,

Currò

et al. 2024

Pharmaceuticals

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“…Another retrospective cohort study comprised of 137 participants reported that 24 patients (17.5%) developed muscle-related adverse reactions such as myalgia, myopathies, etc. [ 35 ]. The most commonly used PCSK9 inhibitors, evolocumab and alirocumab, were found to be associated with musculoskeletal and connective tissue disorders (including back pain, myalgia, pain in extremity, arthralgia, muscle spasms), in a recent retrospective study based on the Food and Drug Administration adverse event reporting system database [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis

Li,

Zang,

et al. 2024

Hum Genomics

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Background Lipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain. Methods Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums. Results Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10− 5) and slower walking pace (OR = 0.918, P = 6.06 × 10− 9). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10− 3), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10− 3) and decelerate walking pace (OR = 0.932, P = 1.43 × 10− 6), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10− 6). Meta-analysis further supported the robustness of these causal associations. Conclusions Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk.

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“…5. Therapeutic effect is severely attenuated due to the development of antibodies 14,15 Tables 6, 7 and 8…”

Section: Advantages Of Pcsk 9 Inhibitorstablementioning

confidence: 99%

Positioning of PCSK9 Inhibitors in hypercholesterolemia

Chaudhry,

Trailokya

2023

IJPP

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PCSK 9 inhibitors currently have a market of 3 billion USD and by next 10 years it will raise to 13 billion USD in developed world. The rising prevalence of dyslipidemia and other lipid disorders are linked to lipid metabolism due to an unbalanced lifestyle and rising alcohol and tobacco use. PCSK9 inhibitors are injectable monoclonal antibodies that inactivate PCSK9 receptors. PCSK9 inhibition decreases degradation of the LDL receptor, thus raising the number of functioning LDL receptors on hepatocytes and lowering the number of LDL particles in the blood, which are atherogenic. For patients with very high cardiovascular risk, PCSK9 inhibitors and ezetimibe are added to statins, where they significantly lower absolute risk for myocardial infarction (MI) and stroke. Statins are known to upregulate PCSK9 encoding gene. PCSK9 inhibitors are given bimonthly or monthly and are reasonably safe. Familial Hypercholesterolemia (FH) a common inherited disorder of lipid metabolism, has mutations in one of these 3 genes: LDLR, APOB or PCSK9. These patients have 22 times more risk of coronary event than general population. Addition of a PCSK9 inhibitor to low dose statin therapy will be more effective in lowering LDL and avoiding the side effects of statins. PCSK9 inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events.

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Muscle-Related Adverse Events Associated With PCSK9 Inhibitors in a Veteran Population

Cited by 4 publications

References 23 publications

Adverse Reactions to Evolocumab: Analysis of Real-World Data from EudraVigilance

Adverse Reactions to Evolocumab: Analysis of Real-World Data from EudraVigilance

Association of lipid-lowering drugs with risk of sarcopenia: a drug target mendelian randomization study and meta-analysis

Positioning of PCSK9 Inhibitors in hypercholesterolemia

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