Evolocumab: rising momentum as novel antidyslipidemic drug

Increased levels of low density lipoprotein cholesterol are responsible for the major cardiovascular events. Low density lipoprotein cholesterol reduction has proved to be highly effective in reducing the risk of major cardiovascular (CV) events in various trials. ACC/AHA guidelines recommend lipid-lowering therapy for patients with known cardiovascular diseases (CVD). Statins are the gold standard treatment for all types hypercholeterolemia but still there is need of some other lipid-lowering therapies especially in patients with statin intolerance and in patients responding inadequately to statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDLC-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. Evolocumab binds to PCSK9 enzyme rendering it unable to bind to the LDLR. More LDLR are available to bind to LDLC. Evolocumab increase the density of LDLR on the surface of hepatocytes, thereby increasing the uptake of LDL particles and decreasing the LDLC in the blood. Evolocumab has proved its efficacy with LDLC reduction from 53% to 75% and associated with minor side effects. Evolocumab has corroborated its effectiveness in reduction in the levels of LDLC. This drug has shown efficacy in heterozygous and homozygous subtypes of familial hypercholesterolemia. Statin intolerance seen in about 15% of all patients restricts the use of first line drug for dyslipidemia. Evolocumab can be a useful option in statin intolerant patients and in patients responding inadequately to statins.

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U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.604736 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiao Gong ◽

Yaqiong Chen ◽

Yusheng Jie ◽

Mingkai Tan ◽

Zhaofang Jiang ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Odds Ratios ◽

Lowering Therapy ◽

Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

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