- •PCSK9 inhibitors are a class of novel, potent lipid-lowering therapies.
- •Respiratory infections are common adverse events reported by PCSK9 inhibitor users.
- •This meta-analysis found no association of PCSK9 inhibitor use with sepsis and severe infections.
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- Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials.J Am Heart Assoc. 2017; 6https://doi.org/10.1161/JAHA.117.006910
- Recognizing Sepsis as a Global Health Priority - A WHO Resolution.N Engl J Med. 2017; 377: 414-417https://doi.org/10.1056/NEJMp1707170
- PCSK9: A Potential Therapeutic Target for Sepsis.J Immunol Res. 2020; 20202687692https://doi.org/10.1155/2020/2687692
- PCSK9 inhibitors in sepsis: a new potential indication?.Expert Opin Investig Drugs. 2017; 26: 137-139https://doi.org/10.1080/13543784.2017.1272570
- A Genetic Approach to the Association Between PCSK9 and Sepsis.JAMA Netw Open. 2019; 2e1911130https://doi.org/10.1001/jamanetworkopen.2019.11130
- PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Sci Transl Med. 2014; 6: 258ra143https://doi.org/10.1126/scitranslmed.3008782
- Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis.J Innate Immun. 2016; 8: 211-220https://doi.org/10.1159/000442976
- Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in Gram positive septic shock patients.Sci Rep. 2019; 9: 10588https://doi.org/10.1038/s41598-019-46745-0
- Impact of PCSK9 loss-of-function genotype on 1-year mortality and recurrent infection in sepsis survivors.EBioMedicine. 2018; 38: 257-264https://doi.org/10.1016/j.ebiom.2018.11.032
- Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department.Clin Exp Med. 2021; 21: 101-107https://doi.org/10.1007/s10238-020-00658-9
- PCSK9 inhibitors for COVID-19: an opportunity to enhance the antiviral action of interferon in patients with hypercholesterolaemia.J Intern Med. 2021; 289: 749-751https://doi.org/10.1111/joim.13210
- Dengue virus induces PCSK9 expression to alter antiviral responses and disease outcomes.J Clin Invest. 2020; 130: 5223-5234https://doi.org/10.1172/JCI137536
- May statins and PCSK9 inhibitors be protective from COVID-19 in familial hypercholesterolemia subjects?.Nutr Metab Cardiovasc Dis. 2020; 30: 1068-1069https://doi.org/10.1016/j.numecd.2020.05.003
- Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience.Clin Pharmacol Ther. 2019; 105: 496-504https://doi.org/10.1002/cpt.1193
Australian product information - Leqvio®(Inclisiran). Accessible from: http://www.guildlink.com.au/gc/ws/nv/pi.cfm?product=nvpleqin. Last Accessed by: 29 Nov 2021.
- PCSK9 and infection: A potentially useful or dangerous association?.J Cell Physiol. 2018; 233: 2920-2927https://doi.org/10.1002/jcp.26040
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.BMJ. 2009; 339: b2700https://doi.org/10.1136/bmj.b2700
Highlights of prescribing information - PRALUENT®(Alirocumab). Accessible from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125559s029s030lbl.pdf; Last Accessed by: 29 Nov 2021.
Highlights of prescribing information - REPATHA® (Evolocumab) Accessible from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125522orig2s000lbl.pdf. Last Accessed by: 29 Nov 2021.
National Institute for Health and Care Excellence (NICE). Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia. Accessible from: https://www.nice.org.uk/guidance/ta733. Last accessed by: 29 Nov 2021.
FDA approves add-on therapy to lower cholesterol among certain high-risk adults. Available from: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-therapy-lower-cholesterol-among-certain-high-risk-adults.
- Study of serious adverse drug reactions using FDA-approved drug labeling and MedDRA.BMC Bioinformatics. 2019; 20: 97https://doi.org/10.1186/s12859-019-2628-5
Department of Health and Human Service. 42CFR Part 11. Clinical Trials Registration and Results Information Submission. Available from: https://www.govinfo.gov/content/pkg/FR-2016-09-21/pdf/2016-22129.pdf.
- Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): A randomised, placebo-controlled, dose-ranging, phase 2 study.The Lancet. 2012; 380: 2007-2017
- Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.JAMA. 2014; 311: 1870-1882https://doi.org/10.1001/jama.2014.4030
- A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.N Engl J Med. 2014; 370: 1809-1819https://doi.org/10.1056/NEJMoa1316222
- ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia.Eur Heart J. 2015; 36: 2996-3003https://doi.org/10.1093/eurheartj/ehv370
- Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N Engl J Med. 2015; 372: 1489-1499https://doi.org/10.1056/NEJMoa1501031
- Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study.Am Heart J. 2015; 169 (e13): 906-915https://doi.org/10.1016/j.ahj.2015.03.004
- A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk.Am J Cardiol. 2016; 117: 40-47https://doi.org/10.1016/j.amjcard.2015.10.021
- A phase III randomized trial evaluating alirocumab 300 mg every 4 weeks as monotherapy or add-on to statin: ODYSSEY CHOICE I.Atherosclerosis. 2016; 254: 254-262https://doi.org/10.1016/j.atherosclerosis.2016.08.043
- Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: the GLAGOV Randomized Clinical Trial.JAMA. 2016; 316: 2373-2384https://doi.org/10.1001/jama.2016.16951
- Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease.N Engl J Med. 2017; 376: 1713-1722https://doi.org/10.1056/NEJMoa1615664
- Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol.N Engl J Med. 2017; 376: 1430-1440
- Efficacy and safety of alirocumab in insulin-treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM-INSULIN randomized trial.Diabetes Obes Metab. 2017; 19: 1781-1792
- Alirocumab and cardiovascular outcomes after acute coronary syndrome.N Engl J Med. 2018; 379: 2097-2107
- Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: primary results of the BERSON clinical trial.Diabetes Obes Metab. 2019; 21: 1455-1463https://doi.org/10.1111/dom.13680
- Efficacy and safety of evolocumab in individuals with type 2 diabetes mellitus: primary results of the randomised controlled BANTING study.Diabetologia. 2019; 62: 948-958https://doi.org/10.1007/s00125-019-4856-7
- Evolocumab in HIV-Infected Patients With Dyslipidemia: Primary Results of the Randomized, Double-Blind BEIJERINCK Study.J Am Coll Cardiol. 2020; 75: 2570-2584
- Inclisiran for the treatment of heterozygous familial hypercholesterolemia.N Engl J Med. 2020; 382: 1520-1530
- Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.N Engl J Med. 2020; 382: 1507-1519https://doi.org/10.1056/NEJMoa1912387
- Alirocumab treatment and neurocognitive function according to the CANTAB scale in patients at increased cardiovascular risk: a prospective, randomized, placebo-controlled study.Atherosclerosis. 2021; 331: 20-27https://doi.org/10.1016/j.atherosclerosis.2021.06.913
- 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.Circulation. 2019; 139: e1082-ee143https://doi.org/10.1161/CIR.0000000000000625
- Long-term impact of sepsis on cardiovascular health.Intensive Care Med. 2019; 45: 78-81https://doi.org/10.1007/s00134-018-5173-1
- Preventing cardiovascular complications of acute infection: a missed opportunity?.Circulation. 2014; 129: 1375-1377https://doi.org/10.1161/CIRCULATIONAHA.114.008712
- Acute pneumonia and the cardiovascular system.Lancet. 2013 Feb 9; 381 (Epub 2013 Jan 16. doi: 10.1016/S0140-6736(12)61266-5): 496-505https://doi.org/10.1016/S0140-6736(12)61266-5
- A systematic review on risk factors associated with sepsis in patients admitted to intensive care units.Aust Crit Care. 2019; 32: 155-164https://doi.org/10.1016/j.aucc.2018.02.005
- The impact of diabetes on the pathogenesis of sepsis.Eur J Clin Microbiol Infect Dis. 2012; 31: 379-388https://doi.org/10.1007/s10096-011-1337-4
- Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?.Lancet Respir Med. 2020; 8: e21https://doi.org/10.1016/S2213-2600(20)30116-8
- PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.J Am Coll Cardiol. 2023; 81: 224-234https://doi.org/10.1016/j.jacc.2022.10.030