Changes in Inflammatory Biomarkers in Patients Treated with Ticagrelor or Clopidogrel

Overview

Journal Clin Cardiol

Specialty Cardiology & Vascular Diseases

Date 2010 Apr 16

PMID 20394040

Citations 21

Authors

Steen Husted

Robert F Storey

Robert A Harrington

Hakan Emanuelsson

Christopher P Cannon

Affiliations

Soon will be listed here.

Abstract

Background: Inflammation is a key factor in the development of atherosclerotic disease and acute coronary syndromes (ACS). The P2Y(12) receptor antagonists ticagrelor (AZD6140) and clopidogrel may have anti-inflammatory effects. The objective of this analysis from the Dose Confirmation Study Assessing Anti-Platelet Effects of AZD6140 vs Clopidogrel in NSTEMI 2 (DISPERSE 2) trial was to compare ticagrelor and clopidogrel for effects on the inflammatory biomarkers C-reactive protein (CRP), interleukin 6 (IL-6), myeloperoxidase (MPO), and soluble CD40 ligand (sCD40L).

Hypothesis: Ticagrelor inhibits the P2Y(12) receptor and inflammation to a greater extent than clopidogrel in nonST-segment elevation ACS (NSTE-ACS) patients.

Methods: In a double-blind, double-dummy, multicenter trial, 990 patients who had been hospitalized within the previous 48 hours with NSTE-ACS were randomized to receive ticagrelor 90 mg twice daily, ticagrelor 180 mg twice daily, or clopidogrel 300 mg initially and then 75 mg once daily. Within the ticagrelor groups, patients were also randomized to receive or not receive a loading dose of ticagrelor 270 mg initially. All patients received standard treatment for ACS, which included 325 mg aspirin initially and 75 to 100 mg aspirin each day subsequently. Inflammatory biomarkers were measured at baseline, upon hospital discharge, and after 4 weeks.

Results: Inflammatory biomarker measurements were not significantly different among treatment groups at baseline, discharge, and 4 weeks.

Conclusions: Ticagrelor and clopidogrel appeared not to differ in this study with respect to the inflammatory biomarkers CRP, IL-6, MPO, and sCD40L in patients with NSTE-ACS.

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References

Yusuf S, Zhao F, Mehta S, Chrolavicius S, Tognoni G, Fox K . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345(7):494-502. DOI: 10.1056/NEJMoa010746. View

Azar R, Kassab R, Zoghbi A, Aboujaoude S, El-Osta H, Ghorra P . Effects of clopidogrel on soluble CD40 ligand and on high-sensitivity C-reactive protein in patients with stable coronary artery disease. Am Heart J. 2006; 151(2):521.e1-521.e4. DOI: 10.1016/j.ahj.2005.10.021. View

Garlichs C, Eskafi S, Raaz D, Schmidt A, Ludwig J, Herrmann M . Patients with acute coronary syndromes express enhanced CD40 ligand/CD154 on platelets. Heart. 2001; 86(6):649-55. PMC: 1730016. DOI: 10.1136/heart.86.6.649. View

Baldus S, Heeschen C, Meinertz T, Zeiher A, Eiserich J, Munzel T . Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 2003; 108(12):1440-5. DOI: 10.1161/01.CIR.0000090690.67322.51. View

Ruggeri Z . Platelets in atherothrombosis. Nat Med. 2002; 8(11):1227-34. DOI: 10.1038/nm1102-1227. View

Armstrong E, Morrow D, Sabatine M . Inflammatory biomarkers in acute coronary syndromes: part I: introduction and cytokines. Circulation. 2006; 113(6):e72-5. DOI: 10.1161/CIRCULATIONAHA.105.595520. View

Saw J, Madsen E, Chan S, Maurer-Spurej E . The ELAPSE (Evaluation of Long-Term Clopidogrel Antiplatelet and Systemic Anti-Inflammatory Effects) study. J Am Coll Cardiol. 2008; 52(23):1826-1833. DOI: 10.1016/j.jacc.2008.08.047. View

Podrez E, Schmitt D, Hoff H, Hazen S . Myeloperoxidase-generated reactive nitrogen species convert LDL into an atherogenic form in vitro. J Clin Invest. 1999; 103(11):1547-60. PMC: 408366. DOI: 10.1172/JCI5549. View

Cannon C, Husted S, Harrington R, Scirica B, Emanuelsson H, Peters G . Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the.... J Am Coll Cardiol. 2007; 50(19):1844-51. DOI: 10.1016/j.jacc.2007.07.053. View

10.

Heeschen C, Dimmeler S, Hamm C, van den Brand M, Boersma E, Zeiher A . Soluble CD40 ligand in acute coronary syndromes. N Engl J Med. 2003; 348(12):1104-11. DOI: 10.1056/NEJMoa022600. View

11.

Cavusoglu E, Ruwende C, Eng C, Chopra V, Yanamadala S, Clark L . Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome. Am J Cardiol. 2007; 99(10):1364-8. DOI: 10.1016/j.amjcard.2006.12.060. View

12.

Hartford M, Wiklund O, Mattsson Hulten L, Perers E, Person A, Herlitz J . CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up. Int J Cardiol. 2006; 108(1):55-62. DOI: 10.1016/j.ijcard.2005.04.004. View

13.

Storey R . Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des. 2006; 12(10):1255-9. DOI: 10.2174/138161206776361318. View

14.

Lucas A, Korol R, Pepine C . Inflammation in atherosclerosis: some thoughts about acute coronary syndromes. Circulation. 2006; 113(17):e728-32. DOI: 10.1161/CIRCULATIONAHA.105.601492. View

15.

Molero L, Lopez-Farre A, Mateos-Caceres P, Fernandez-Sanchez R, Maestro M, Silva J . Effect of clopidogrel on the expression of inflammatory markers in rabbit ischemic coronary artery. Br J Pharmacol. 2005; 146(3):419-24. PMC: 1576286. DOI: 10.1038/sj.bjp.0706340. View

16.

Morrow D, Rifai N, Antman E, Weiner D, McCabe C, Cannon C . C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol. 1998; 31(7):1460-5. DOI: 10.1016/s0735-1097(98)00136-3. View

17.

Wallentin L, Becker R, Budaj A, Cannon C, Emanuelsson H, Held C . Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11):1045-57. DOI: 10.1056/NEJMoa0904327. View

18.

Tousoulis D, Antoniades C, Koumallos N, Stefanadis C . Pro-inflammatory cytokines in acute coronary syndromes: from bench to bedside. Cytokine Growth Factor Rev. 2006; 17(4):225-33. DOI: 10.1016/j.cytogfr.2006.04.003. View

19.

Storey R, Husted S, Harrington R, Heptinstall S, Wilcox R, Peters G . Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol. 2007; 50(19):1852-6. DOI: 10.1016/j.jacc.2007.07.058. View

20.

Bisoendial R, Kastelein J, Peters S, Levels J, Birjmohun R, Rotmans J . Effects of CRP infusion on endothelial function and coagulation in normocholesterolemic and hypercholesterolemic subjects. J Lipid Res. 2007; 48(4):952-60. DOI: 10.1194/jlr.P600014-JLR200. View