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Journal of Drug Assessment Volume 8, 2019 - Issue 1
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Cardiovascular Medicine

Investigating the lowest threshold of vascular benefits from LDL cholesterol lowering with a PCSK9 mAb inhibitor (alirocumab) in healthy volunteers – a mechanistic physiological study (INTENSITY-LOW): protocol and study rationale

Michael S. KostapanosDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK; ;Lipid Clinic, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Correspondence[email protected]
,
Paul J. CacciottoloDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK;
,
Annette HubschDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK;
,
Holly PaveyCardiovascular Trials Office, Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UKORCID Iconhttp://orcid.org/0000-0001-5014-5118
ORCID Icon,
James HurlockCardiovascular Trials Office, Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
,
Kaisa Maki-PetajaDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK;
,
Ian B. WilkinsonDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK; ;Cardiovascular Trials Office, Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
&
Joseph CheriyanDivision of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK; ;Cardiovascular Trials Office, Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
 show all
Pages 167-174 | Received 10 Jun 2019, Accepted 25 Sep 2019, Published online: 24 Oct 2019

References

  • Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;104(10):1108–1113.
  • Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–590.
  • Lind L, Berglund L, Larsson A, et al. Endothelial function in resistance and conduit arteries and 5-year risk of cardiovascular disease. Circulation. 2011;123(14):1545–1551.
  • Hingorani AD, Cross J, Kharbanda RK, et al. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation. 2000;102(9):994–999.
  • Wierzbicki AS, Chowienczyk PJ, Cockcroft JR, et al. Cardiovascular risk factors and endothelial dysfunction. Clin Sci. 2004;107(6):609–615.
  • Kostapanos MS, Florentin M, Elisaf MS, et al. Hemostatic factors and the metabolic syndrome. CVP. 2014;11(6):880–905.
  • Sun ZDY, Cheriyan J. Non-invasive measurements of arterial function: What? When? Why should we use them? Heart. 2019;105(15):1203–1211.
  • Wilkinson IB, Webb DJ. Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications. Br J Clin Pharmacol. 2001;52(6):631–646.
  • Heitzer T, Schlinzig T, Krohn K, et al. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001;104(22):2673–2678.
  • Laurent S, Cockcroft J, Van Bortel L, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–2605.
  • Kostapanos MS, Milionis HJ, Elisaf MS. An overview of the extra-lipid effects of rosuvastatin. J Cardiovasc Pharm T. 2008;13(3):157–174.
  • Westerink J, Deanfield JE, Imholz BP, et al. High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study. Atherosclerosis. 2013;227(1):118–124.
  • Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
  • Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722.
  • Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097–2107.
  • Roth EM, Taskinen MR, Ginsberg HN, et al. 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.
  • Soran H, Dent R, Durrington P. Evidence-based goals in LDL-C reduction. Clin Res Cardiol. 2017;106(4):237–248.
  • Kostapanos MS, Elisaf MS. JUPITER and satellites: Clinical implications of the JUPITER study and its secondary analyses. WJC. 2011;3(7):207–214.
  • Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–2207.
  • Lind L. Relationships between three different tests to evaluate endothelium-dependent vasodilation and cardiovascular risk in a middle-aged sample. J Hypertens. 2013;31(8):1570–1574.
  • https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice.
  • O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation. 1997;95(5):1126–1131.
  • Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149–1158.
  • Stern RH, Yang BB, Hounslow NJ, et al. Pharmacodynamics and pharmacokinetic-pharmacodynamic relationships of atorvastatin, an HMG-CoA reductase inhibitor. J Clin Pharmacol. 2000;40(6):616–623.
  • Stein EA, Mellis S, Yancopoulos GD, et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012;366(12):1108–1118.
  • Stewart J, Breslin WJ, Beyer BK, et al. Birth control in clinical trials: industry survey of current use practices, governance, and monitoring. Drug Inf J. 2016;50(2):155–168.

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