PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.
PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.
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在新型冠状病毒感染的炎症阶段抑制PCSK9
DOI：
10.1016/j.jacc.2022.10.030
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发表时间：
2023-01-24
影响因子：
24
通讯作者：
Kubica, Jacek
中科院分区：
文献类型：
--
作者：
Navarese, Eliano P.;Podhajski, Przemyslaw;Gurbel, Paul A.;Grzelakowska, Klaudyna;Ruscio, Eleonora;Tantry, Udaya;Magielski, Przemyslaw;Kubica, Aldona;Niezgoda, Piotr;Adamski, Piotr;Junik, Roman;Przybylski, Grzegorz;Pilaczynska-Cemel, Marta;Rupji, Manali;Specchia, Giuseppe;Pinkas, Jaroslaw;Gajda, Robert;Gorog, Diana A.;Andreotti, Felicita;Kubica, Jacek
新冠肺炎期间炎症的强度与不良结果有关。枯草杆菌前蛋白转换酶9参与低密度脂蛋白受体的稳态，对血管炎症和新冠肺炎炎症反应具有潜在的影响。这项研究的目的是研究抑制PCSK9与安慰剂对重症新冠肺炎患者临床和实验室结果的影响。在这项双盲、安慰剂对照的多中心试点试验中，60名因严重新冠肺炎而住院的患者，患有磨玻璃样浑浊肺炎，动脉血氧分压与吸入氧分压之比为300m m/≤，被随机分为1：1接受单次140毫克的挥发单抗或安慰剂皮下注射。主要终点是30天时死亡或需要插管。主要次要终点是从基线开始7天和30天循环白细胞介素6的变化。随机接受PCSK9抑制剂的患者在30天内的死亡率或需要插管的比率低于安慰剂组(23.3%对53.3%，风险差异：-30%；95%可信区间：-53.40%至-6.59%)。服用PCSK9抑制剂的患者血清IL-6水平低于服用安慰剂的患者(30天下降幅度：-56%比-21%)。基线IL-6高于中位数的患者接受PCSK9抑制与安慰剂相比死亡率较低(风险差异：-37.50%；95%可信区间：-68.20%至-6.70%)。与安慰剂相比，抑制PCSK9降低了重症新冠肺炎患者死亡或需要插管的主要终点和IL-6水平。在随机分组中，炎症程度越严重的患者在PCSK9抑制组与安慰剂组相比存活率更高，这表明炎症强度可能会推动治疗效果。[抑制PCSK9对新冠肺炎炎症阶段患者临床结局的影响[IMPACT-SIRIO 5]；NCT04941105)
The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: –56% vs –21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: –37.50%; 95% CI: –68.20% to –6.70%). PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105)
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影响因子：
3.7
作者：
Sabaka P;Koščálová A;Straka I;Hodosy J;Lipták R;Kmotorková B;Kachlíková M;Kušnírová A
通讯作者：
Kušnírová A
影响因子：
4.6
作者：
Corradini E;Ventura P;Ageno W;Cogliati CB;Muiesan ML;Girelli D;Pirisi M;Gasbarrini A;Angeli P;Querini PR;Bosi E;Tresoldi M;Vettor R;Cattaneo M;Piscaglia F;Brucato AL;Perlini S;Martelletti P;Pontremoli R;Porta M;Minuz P;Olivieri O;Sesti G;Biolo G;Rizzoni D;Serviddio G;Cipollone F;Grassi D;Manfredini R;Moreo GL;Pietrangelo A;SIMI-COVID-19 Collaborators
通讯作者：
SIMI-COVID-19 Collaborators
影响因子：
4.6
作者：
Ricci C;Ruscica M;Camera M;Rossetti L;Macchi C;Colciago A;Zanotti I;Lupo MG;Adorni MP;Cicero AFG;Fogacci F;Corsini A;Ferri N
通讯作者：
Ferri N
影响因子：
3.7
作者：
Ghati, Nirmal;Bhatnagar, Sushma;Mahendran, Manjit;Thakur, Abhishek;Prasad, Kshitij;Kumar, Devesh;Dwivedi, Tanima;Mani, Kalaivani;Tiwari, Pawan;Gupta, Ritu;Mohan, Anant;Saxena, Anita;Guleria, Randeep;Deepti, Siddharthan
通讯作者：
Deepti, Siddharthan
影响因子：
3.1
作者：
Dwivedi, Dhruva J.;Grin, Peter M.;Liaw, Patricia C.
通讯作者：
Liaw, Patricia C.