|
|
|
| Research progress of proprotein convertase subtilin Kexin-9 inhibitor in lipid-lowering therapy |
| PAN Haiqiang1 CHEN Xiaojia2 LI Caihong2 ZHANG Zhizhen2 |
1.School of Medical Technology, Guangdong Medical University, Guangdong Province, Dongguan 523808, China;
2.School of Basic Medicine, Guangdong Medical University, Guangdong Province, Dongguan 523808, China
|
|
|
|
Abstract Proprotein convertase subtilisin Kexin type 9 (PCSK9) has become an essential target for regulating low-density lipoprotein cholesterol (LDL-C) level. PCSK9 inhibitors significantly reduces plasma LDL-C level, Statins also reduces LDL-C level but raises PCSK9 level. A quantity of clinical trials has verified the efficacy and safety of Statins in combination with PCSK9 inhibitors. Although different types of PCSK9 inhibitor act in varying ways, their effects are the same in different patients, and the ongoing clinical trials will further demonstrate their safety and role in reducing cardiovascular risk.
|
|
|
|
|
|
[1] Del Pinto R，Grassi D，Properzi G，et al. Low Density Lipoprotein（LDL）Cholesterol as a Causal Role for Atherosclerotic Disease：Potential Role of PCSK9 Inhibitors [J]. High Blood Press Cardiovasc Prev，2019，26（3）：199-207.
[2] Auer J，Weber T，Eber B. Intensive versus moderate lipid lowering with statins after acute coronary syndromes [J]. N Engl J Med，2004，351（7）：714-717.
[3] Group HTC. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment [J]. Eur Heart J，2013， 34（17）：1279-1291.
[4] Santulli G，Jankauskas SS，Gambardella J. Inclisiran：a new milestone on the PCSK9 road to tackle cardiovascular risk [J]. Eur Heart J Cardiovasc Pharmacother，2021，7（3）：e11-e12.
[5] Ding Z，Pothineni NVK，Goel A，et al. PCSK9 and inflammation: role of shear stress, pro-inflammatory cytokines, and LOX-1 [J]. Cardiovasc Res，2020，116（5）：908-915.
[6] Tam J，Thankam F，Agrawal DK，et al. Critical Role of LOX- 1-PCSK9 Axis in the Pathogenesis of Atheroma Formation and Its Instability [J]. Heart Lung Circ，2021，30（10）：1456- 1466.
[7] Adorni MP，Cipollari E，Favari E，et al. Inhibitory effect of PCSK9 on Abca1 protein expression and cholesterol efflux in macrophages [J]. Atherosclerosis，2017，256：1-6.
[8] Cholesterol Treatment Trialists C，Baigent C，Blackwell L，et al. Efficacy and safety of more intensive lowering of LDL cholesterol：a meta-analysis of data from 170,000 participants in 26 randomised trials [J]. Lancet，2010，376（9753）：1670-1681.
[9] Dettlaff-Pokora A，Sucajtys-Szulc E，Sledzinski T. Up-regulation of PCSK9 gene expression and diminished level of LDL-receptor in rat liver as a potential cause of post-lipectomy hypercholesterolemia [J]. Mol Cell Biochem，2019，455（1/2）：207-217.
[10] 胡大一，郭艺芳.《2014年中国胆固醇教育计划血脂异常防治专家建议》十大要点[J].中国循环杂志，2014，29（6）：410-411.
[11] 中国胆固醇教育计划（CCEP）工作委员会，中国医疗保健国际交流促进会动脉粥样硬化血栓疾病防治分会，中国老年学和老年医学学会心血管病分会，等.中国胆固醇教育计划调脂治疗降低心血管事件专家建议（2019）[J].中华内科杂志，2020，59（1）：18-22.
[12] Raal FJ，Stein EA，Dufour R，et al. PCSK9 inhibition with evolocumab（AMG 145）in heterozygous familial hypercholesterolaemia（RUTHERFORD-2）：a randomised, double-blind, placebo-controlled trial [J]. Lancet，2015，385（9965）：331-340.
[13] Koren MJ，Sabatine MS，Giugliano RP，et al. Long-Term Efficacy and Safety of Evolocumab in Patients With Hypercholesterolemia [J]. J Am Coll Cardiol，2019，74（17）：2132- 2146.
[14] Sabatine MS，Leiter LA，Wiviott SD，et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes：a prespecified analysis of the FOURIER randomised controlled trial [J]. Lancet Diabetes Endocrinol，2017，5（12）：941-950.
[15] Bohula EA，Giugliano RP，Leiter LA，et al. Inflammatory and Cholesterol Risk in the FOURIER Trial [J]. Circulation，2018，138（2）：131-140.
[16] Charytan DM，Sabatine MS，Pedersen TR，et al. Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial [J]. J Am Coll Cardiol，2019，73（23）：2961-2970.
[17] Boccara F，Kumar PN，Caramelli B，et al. Evolocumab in HIV-Infected Patients With Dyslipidemia：Primary Results of the Randomized, Double-Blind BEIJERINCK Study [J]. J Am Coll Cardiol，2020，75（20）：2570-2584.
[18] Schwartz GG，Steg PG，Szarek M，et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome [J]. N Engl J Med，2018，379（22）：2097-2107.
[19] Hoogeveen RM，Opstal TSJ，Kaiser Y，et al. PCSK9 Antibody Alirocumab Attenuates Arterial Wall Inflammation Without Changes in Circulating Inflammatory Markers [J]. JACC Cardiovasc Imaging，2019，12（12）：2571-2573.
[20] Ying Q，Chan DC，Pang J，et al. PCSK9 inhibition with alirocumab decreases plasma lipoprotein（a） concentration by a dual mechanism of action in statin-treated patients with very high apolipoprotein（a） concentration [J]. J Intern Med，2022，291（6）：870-876.
[21] Goodman SG，Aylward PE，Szarek M，et al. Effects of Aliro- cumab on Cardiovascular Events After Coronary Bypass Surgery [J]. J Am Coll Cardiol，2019，74（9）：1177-1186.
[22] Damask A，Steg PG，Schwartz GG，et al. Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Aliroc- umab Treatment in the ODYSSEY OUTCOMES Trial [J]. Circulation，2020，141（8）：624-636.
[23] Jukema JW，Zijlstra LE，Bhatt DL，et al. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES [J]. Circulation，2019， 140（25）：2054-2062.
[24] Ray KK，Colhoun HM，Szarek M，et al. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes：a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial [J]. Lancet Diabetes Endocrinol，2019，7（8）：618-628.
[25] Ray KK，Leiter LA，Müller-Wieland D，et al. Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia：The ODYSSEY DM-DYSLIPIDEMIA randomized trial [J]. Diabetes Obes Metab，2018，20（6）：1479-1489.
[26] Tu?觡ón J，Steg PG，Bhatt DL，et al. Effect of alirocumab on major adverse cardiovascular events according to renal function in patients with a recent acute coronary syndrome：prespecified analysis from the ODYSSEY OUTCOMES randomized clinical trial [J]. Eur Heart J，2020，41（42）：4114-4123.
[27] 张峰，金琴花.急性冠状动脉综合征患者血脂管理临床路径专家共识[J].中国循环杂志，2020，35（10）：941-947.
[28] Rogula S，Blazejowska E，Gasecka A，et al. Inclisiran-Silencing the Cholesterol, Speaking up the Prognosis [J]. J Clin Med，2021，10（11）：2467.
[29] Landmesser U，Haghikia A，Leiter LA，et al. Effect of inclisiran, the small-interfering RNA against proprotein convertase subtilisin/kexin type 9，on platelets，immune cells，and immunological biomarkers：a pre-specified analysis from ORION-1 [J]. Cardiovasc Res，2021，117（1）：284-291.
[30] Hovingh GK，Lepor NE，Kallend D，et al. Inclisiran Durably Lowers Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin/Kexin Type 9 Expression in Homozygous Familial Hypercholesterolemia：The ORION-2 Pilot Study [J]. Circulation，2020，141（22）：1829-1831.
[31] Wright RS，Ray KK，Raal FJ，et al. Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis [J]. J Am Coll Cardiol，2021，77（9）：1182-1193.
[32] Cordero A，Santos-Gallego CG，Facila L，et al. Estimation of the major cardiovascular events prevention with Inclisiran [J]. Atherosclerosis，2020，313：76-80. |
|
|
|
