Top

BMC Cardiovascular Disorders

Published in:

01-12-2021 | Statins | Research article

Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

Authors: Tingting Li, Yingyi Zhang, Hongliang Cong

Published in: BMC Cardiovascular Disorders | Issue 1/2021

Abstract

Background

To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.

Methods

A total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.

Results

In the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01).

Conclusions

Evolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.

European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, Agewall S, Alegria E, Chapman MJ, Durrington P, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769–818.CrossRef

Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45.PubMedCrossRef

Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC Jr. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 2011a;5(2):105–13.PubMedPubMedCentralCrossRef

Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9.PubMedCrossRef

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.PubMedCrossRef

Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, Wilson PW, D’Agostino RB. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study—implications for LDL Management. J Clin Lipidol. 2007;1(6):583–92.PubMedPubMedCentralCrossRef

Langlois MR, Chapman MJ, Cobbaert C, Mora S, Remaley AT, Ros E, Watts GF, Borén J, Baum H, Bruckert E, et al. European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative. Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM. Clin Chem. 2018;64(7):1006–33.PubMedCrossRef

Goliasch G, Oravec S, Blessberger H, Dostal E, Hoke M, Wojta J, Schillinger M, Huber K, Maurer G, Wiesbauer F. Relative importance of different lipid risk factors for the development of myocardial infarction at a very young age (≤ 40 years of age). Eur J Clin Invest. 2012;42(6):631–6.PubMedCrossRef

AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices, Cole TG, Contois JH, Csako G, McConnell JP, Remaley AT, Devaraj S, Hoefner DM, Mallory T, Sethi AA, Warnick GR. Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices. Clin Chem. 2013;59(5):752–70.CrossRef

10.

Mora S, Buring JE, Ridker PM. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014;129:553–61.PubMedCrossRef

11.

12.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, et al. FOURIER Steering committee and investigators: evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.CrossRefPubMed

13.

Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJ, Koenig W, Somaratne R, Kassahun H, Yang J, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial. JAMA. 2016;316(22):2373–84.CrossRefPubMed

14.

Zhang XC, Yu XZ, Chen FY, Zhu HD. Emergency rapid diagnosis and treatment guidelines for acute coronary syndrome (2019). J Clin Emerg. 2019;20(04):253–62.

15.

Jeyarajah EJ, Cromwell WC, Otvos JD. Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med. 2006;26:847–70.CrossRefPubMed

16.

Jiménez B, Holmes E, Heude C, Tolson RF, Harvey N, Lodge SL, Chetwynd AJ, Cannet C, Fang F, Pearce JTM, et al. Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial. Anal Chem. 2018;90(20):11962–71.CrossRefPubMed

17.

Dona AC, Jiménez B, Schäfer H, Humpfer E, Spraul M, Lewis MR, Pearce JT, Holmes E, Lindon JC, Nicholson JK. Precision high-throughput proton NMR spectroscopy of human urine, serum, and plasma for large-scale metabolic phenotyping. Anal Chem. 2014;86(19):9887–94.CrossRefPubMed

18.

Harbaum L, Ghataorhe P, Wharton J, Jiménez B, Howard LSG, Gibbs JSR, Nicholson JK, Rhodes CJ, Wilkins MR. Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension. Thorax. 2019;74(4):380–9.CrossRefPubMed

19.

Okazaki M, Usui S, Ishigami M, Sakai N, Nakamura T, Matsuzawa Y, Yamashita S. Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography. Arterioscler Thromb Vasc Biol. 2005;25(3):578–84.CrossRefPubMed

20.

Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, et al. DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014;370(19):1809–19.PubMedCrossRef

21.

Roth EM, Taskinen MR, Ginsberg HN, Kastelein JJ, Colhoun HM, Robinson JG, Merlet L, Pordy R, Baccara-Dinet MT. Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: results of a 24 week, double-blind, randomized Phase 3 trial. Int J Cardiol. 2014;176(1):55–61.PubMedCrossRef

22.

Koren MJ, Lundqvist P, Bolognese M, Neutel JM, Monsalvo ML, Yang J, Kim JB, Scott R, Wasserman SM, Bays H, MENDEL-2 Investigators. Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol. 2014;63(23):2531–40.PubMedCrossRef

23.

Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Després JP. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Circulation. 1997;95(1):69–75.PubMedCrossRef

24.

Galeano NF, Al-Haideri M, Keyserman F, Rumsey SC, Deckelbaum RJ. Small dense low density lipoprotein has increased affinity for LDL receptorindependent cell surface binding sites: a potential mechanism for increased atherogenicity. J Lipid Res. 1998;39:1263–73.PubMed

25.

Toft-Petersen AP, Tilsted HH, Aarøe J, Rasmussen K, Christensen T, Griffin BA, Aardestrup IV, Andreasen A, Schmidt EB. Small dense LDL particles–a predictor of coronary artery disease evaluated by invasive and CT-based techniques: a case-control study. Lipids Health Dis. 2011;10:21.PubMedPubMedCentralCrossRef

26.

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, et al. Odyssey Outcomes Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–107.PubMedCrossRef

27.

Koren MJ, Kereiakes D, Pourfarzib R, Winegar D, Banerjee P, Hamon S, Hanotin C, McKenney JM. Effect of PCSK9 inhibition by Alirocumab on lipoprotein particle concentrations determined by nuclear magnetic resonance spectroscopy. J Am Heart Assoc. 2015;4(11):e002224.PubMedPubMedCentralCrossRef

28.

Toth PP, Sattar N, Blom DJ, Martin SS, Jones SR, Monsalvo ML, Elliott M, Davis M, Somaratne R, Preiss D. Effect of Evolocumab on lipoprotein particles. Am J Cardiol. 2018;121(3):308–14.PubMedCrossRef

29.

Krauss RM. All low-density lipoprotein particles are not created equal. Arterioscler Thromb Vasc Biol. 2014;34:959–61.PubMedCrossRef

30.

Mora S, Caulfield MP, Wohlgemuth J, Chen Z, Superko HR, Rowland CM, Glynn RJ, Ridker PM, Krauss RM. Atherogenic lipoprotein subfractions determined by ion mobility and first cardiovascular events after random allocation to high-intensity statin or Placebo: the justification for the use of statins in prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial. Circulation. 2015;132(23):2220–9.PubMedPubMedCentralCrossRef

31.

China Cholesterol Education Program Working committee. 2019 Expert recommendations of the China Cholesterol Education Program (CCEP) for lipid-lowering therapy to reduce cardiovascular events. Chin J Internal Med. 2020;1:18–22.

32.

Fox KA, Anderson FA Jr, Goodman SG, Steg PG, Pieper K, Quill A, Gore JM, GRACE Investigators. Time course of events in acute coronary syndromes: implications for clinical practice from the GRACE registry. Nat Clin Pract Cardiovasc Med. 2008;5(9):580–9.PubMedCrossRef

33.

Gallone G, Baldetti L, Pagnesi M, Latib A, Colombo A, Libby P, Giannini F. Medical therapy for long-term prevention of atherothrombosis following an acute coronary syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018;72:2886–903.PubMedCrossRef

34.

Authors/Task Force Members, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies. ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;2019(290):140–205.

Title: Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes
Authors: Tingting Li
Yingyi Zhang
Hongliang Cong
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Statins
PCSK9 Inhibitor
Acute Coronary Syndrome
Evolocumab
Published in: BMC Cardiovascular Disorders / Issue 1/2021
Electronic ISSN: 1471-2261
DOI: https://doi.org/10.1186/s12872-020-01827-0

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

At a glance: The STEP trials

Springer Medicine

Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Second-hand smoking, hypertension and cardiovascular risk: findings from Peru

Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15)

Chronic polytherapy after myocardial infarction: the trade-off between hospital and community-based providers in determining adherence to medication

Baseline pro-inflammatory gene expression in whole blood is related to adverse long-term outcomes after transcatheter aortic valve replacement: a case control study

Pediatric In-Hospital Cardiac Arrest International Registry (PACHIN): protocol for a prospective international multicenter register of cardiac arrest in children

Association of ACE2 variant rs4646188 with the risks of atrial fibrillation and cardioembolic stroke in Uygur patients with type 2 diabetes

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page