Changes in inflammatory biomarkers in patients treated with ticagrelor or clopidogrel.
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).


OBJECTIVE
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.
Husted
Steen
S
Arhus University Hospital, Arhus, Denmark. steehust@rm.dk
Storey
Robert F
RF
Harrington
Robert A
RA
Emanuelsson
Håkan
H
Cannon
Christopher P
CP
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D015415:Biomarkers; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D023201:CD40 Ligand; D002097:C-Reactive Protein; D000077144:Clopidogrel; D009195:Peroxidase; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine; D001241:Aspirin
N Engl J Med. 2001 Aug 16;345(7):494-502
11519503
Am Heart J. 2006 Feb;151(2):521.e1-521.e4
16442924
Heart. 2001 Dec;86(6):649-55
11711459
Circulation. 2003 Sep 23;108(12):1440-5
12952835
Nat Med. 2002 Nov;8(11):1227-34
12411949
Circulation. 2006 Feb 14;113(6):e72-5
16476853
J Am Coll Cardiol. 2008 Dec 2;52(23):1826-1833
19038679
J Clin Invest. 1999 Jun;103(11):1547-60
10359564
J Am Coll Cardiol. 2007 Nov 6;50(19):1844-51
17980250
N Engl J Med. 2003 Mar 20;348(12):1104-11
12646667
Am J Cardiol. 2007 May 15;99(10):1364-8
17493461
Int J Cardiol. 2006 Mar 22;108(1):55-62
16516698
Curr Pharm Des. 2006;12(10):1255-9
16611109
Circulation. 2006 May 2;113(17):e728-32
16651475
Br J Pharmacol. 2005 Oct;146(3):419-24
16041401
J Am Coll Cardiol. 1998 Jun;31(7):1460-5
9626820
N Engl J Med. 2009 Sep 10;361(11):1045-57
19717846
Cytokine Growth Factor Rev. 2006 Aug;17(4):225-33
16750416
J Am Coll Cardiol. 2007 Nov 6;50(19):1852-6
17980251
J Lipid Res. 2007 Apr;48(4):952-60
17259597
Circulation. 1999 Apr 27;99(16):2079-84
10217645
Lancet. 1996 Nov 16;348(9038):1329-39
8918275
Int J Cardiol. 2007 Feb 14;115(3):361-5
16887214
Eur J Clin Invest. 2009 Mar;39(3):174-82
19260946
Platelets. 2009 Feb;20(1):50-7
19172522
Atherosclerosis. 2007 Oct;194(2):397-402
16962598
Clin Chem. 2007 Jul;53(7):1231-4
17495016
Br J Haematol. 2001 Oct;115(1):3-12
11722403
Nutr Rev. 2007 Dec;65(12 Pt 2):S253-9
18240558
Blood. 2005 Jan 15;105(2):526-32
15374879
Chin Med J (Engl). 2006 Jan 5;119(1):32-6
16454979
Am J Med Sci. 2006 Oct;332(4):186-97
17031244
Circulation. 2003 Sep 2;108(9):1049-52
12912804
Eur Heart J. 2006 May;27(9):1038-47
16476694
Am J Cardiol. 2009 Jun 1;103(11):1546-50
19463513
Circulation. 2000 Mar 28;101(12):1372-8
10736279
Curr Opin Crit Care. 2006 Oct;12(5):412-9
16943718
Thromb Res. 2010 Apr;125(4):309-14
19604542
Clin Chem. 2007 Oct;53(10):1800-7
17717132
J Thromb Haemost. 2004 Nov;2(11):1934-40
15550024