Effects of evolocumab therapy and low LDL‐C levels on vitamin E and steroid hormones in Chinese and global patients with type 2 diabetes

Blom, Dirk; Chen, Jiyan; Yuan, Zuyi; Borges, João Lindolfo Cunha; Monsalvo, Maria Laura; Wang, Nan; Hamer, Andrew; Ge, Junbo

doi:10.1002/edm2.123

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…Their economic value has been assessed by using simulation models with distinct sets of assumptions. Findings comparing PCSK9 inhibitors with statin therapy for secondary prevention showed higher cost-effectiveness ratios from $141,700 to $450,000 per QALY added for the first group, at mid-2018 prices [42]. In addition, in cases with baseline LDL − C levels ≥ 119 mg/dL, lower PCSK9 inhibitor therapy instead of ≥70 mg/dL (≥1.8 mmol/L) resulted in greater cost-effectiveness to $150,000 per QALY added versus $268000.…”

Section: Cost-effectiveness and Accessibility Of Pcsk9 Inhibitorsmentioning

confidence: 99%

Genetics, Safety, Cost-Effectiveness, and Accessibility of Injectable Lipid-Lowering Agents: A Narrative Review

Sindi

2023

Journal of Lipids

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Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased incidence; thus, since a long time, low-density lipoprotein cholesterol-lowering therapies have been employed to reduce coronary artery disease-associated mortality. The first-line therapy for hyperlipidemia and dyslipidemia is statins. Evidence showed that statins decrease the level of LDL-C resulting in a lower risk of CVD (20-25% for every decrease of 1 mmol/L). However, due to statin intolerance in some patients and despite using maximal doses, they have not been successful in lowering cardiovascular-associated mortality. Moreover, bococizumab was recently suspended due to its higher immunogenicity with time, resulting in less efficacy with long-term use. Alternatives to statins are PCSK9 inhibitors which are administered subcutaneously every two or four weeks. They are injectables with considerable lipid-lowering properties. This narrative review discusses their genetics, safety, tolerability, and cost-effectiveness. It also quantifies their benefit in certain subgroups by analyzing the findings from recent randomized clinical trials. Current data from phase 2 and 3 trials (ORION, ODYSSEY, and FOURIER) suggest a favorable profile for evolocumab, alirocumab, and inclisiran with minimal tolerable side effects and superior efficacy in statin-intolerant patients. Their cost-effectiveness has not yet been established clearly, but future outcomes seem promising.

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Section: Cost-effectiveness and Accessibility Of Pcsk9 Inhibitorsmentioning

confidence: 99%

Genetics, Safety, Cost-Effectiveness, and Accessibility of Injectable Lipid-Lowering Agents: A Narrative Review

Sindi

2023

Journal of Lipids

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“…Although absolute vitamin E serum levels were reduced by 23% in patients treated with evolocumab, vitamin E concentrations normalized for plasma lipid concentrations (LDL-C, ApoB, and non-HDL-C) did not decrease. 60 Finally, in a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with HeFH (HAUSER-RCT), evolocumab reduced LDL-C levels by 44.5%. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab group and the placebo group.…”

Section: Effect Of Pcsk9 Inhibitor Therapy On Vitamin E and Other Fatmentioning

confidence: 99%

Section: Effect Of Pcsk9 Inhibitor Therapy On Vitamin E and Other Fatmentioning

confidence: 99%

“… OSLER-1 Extension Study 34 Open-label, phase 2 RCT 1324 participants on SOC therapy Evolocumab + SOC therapy vs SOC therapy alone for up to 4 years Evolocumab did not increase new-onset DM (2.8% vs 4%), neurocognitive events (0.4% vs 0%), or muscle-related events (4.7% vs 8.5%) ODYSSEY ALTERNATIVE 44 Double-blind, double-dummy, active-controlled, parallel-group, phase 3 RCT 314 patients at moderate or high CVD risk, with statin intolerance, confirmed by statin rechallenge arm Alirocumab or ezetimibe or atorvastatin for 24 weeks Decreased musculoskeletal events with alirocumab vs atorvastatin (HR:0.61; P=0.042) GAUSS-3 45 Double-blind, multicenter, phase 3 RCT 218 patients with statin intolerance, confirmed by statin rechallenge procedure Alirocumab or ezetimibe for 24 weeks Decreased muscle symptoms (20.7% vs 28.8%) and drug-discontinuation rates (0.7% vs 6.8%) in the evolocumab group compared to the ezetimibe group. EBBINGHAUS 51 Double-blind, placebo-controlled, multicenter, phase 3 RCT 1204 patients with ASCVD, LDL-C ≥ 70mg/dl or non-HDL-C ≥100mg/dl, on moderate-intensity or high-intensity statin therapy Evolocumab vs placebo for a median of 19 months No significant difference in cognitive function, including the spatial working memory strategy index of executive function, as well as working memory, episodic memory and psychomotor speed DESCARTES 56 Double-blind, placebo-controlled, multicenter, phase 3 RCT 818 patients with LDL-C ≥75mg/dl, fasting triglycerides ≤ 400mg/dl Evolocumab for 52 weeks vs placebo With evolocumab, vitamin E levels did not decrease after normalization for cholesterol, tissue vitamin E levels did not change, and steroid or gonadal hormone synthesis was not affected Prespecified analysis of BERSON 60 Double-blind, placebo-controlled, multicenter, phase 3 RCT 981 patients with DM and hyperlipidemia or mixed dyslipidemia, LDL-C ≥100 mg/dl, on statin therapy Evolocumab for 12 weeks vs placebo With evolocumab, vitamin E levels did not decrease after normalization for plasma lipid concentrations (LDL-C, ApoB, and non-HDL-C), and there was no change in steroid hormone or gonadotro...…”

Section: Effect Of Pcsk9 Inhibitor Therapy On Vitamin E and Other Fatmentioning

confidence: 99%

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<p>Safety and Tolerability of PCSK9 Inhibitors: Current Insights</p>

Kosmas¹,

Skavdis²,

Sourlas³

et al. 2020

CPAA

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The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.

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“…In short-term studies of evolocumab, serum vitamin E concentrations mirrored the changes in lipid fraction without altering tissue levels. 6 7 Furthermore, there was no evidence of an effect on steroid hormone metabolism.…”

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confidence: 97%