title: Thrombus and antiplatelet therapy in type 2 diabetes mellitus. A prospective study after non-ST elevation acute coronary syndrome and a randomised, blinded, placebo-controlled study in stable angina.
abstract: Type 2 diabetes mellitus (T2DM) is associated with higher rates of thrombotic complications in patients with coronary artery disease (CAD) despite optimal medical therapy. Thrombus area was measured in T2DM and non-diabetic patients receiving aspirin and clopidogrel 7-10 days after troponin positive Non ST-elevation acute coronary syndrome (NSTE-ACS). Secondly, we assessed response to clopidogrel in naive patients with T2DM and stable CAD in a randomised controlled trial. Thrombus area was measured by Badimon chamber and platelet reactivity by VerifyNow®. In T2DM patients presenting with NSTE-ACS, thrombus area was greater compared to non-diabetic patients (mean ± SD, 20,512 ± 12,567 [n=40] vs. 14,769 ± 8,531 [n=40] μm²/mm, p=0.02) Clopidogrel decreased thrombus area among stable CAD patients with T2DM (mean ± SD, Clopidogrel [n=45]: 13,978 ± 5,502 to 11,192 ± 3,764 μm²/mm vs. placebo [n=45]: 13,959 ± 7,038 to 14,201 ± 6,780 μm²/mm, p<0.001, delta values: clopidogrel vs. placebo, mean ± SD, 2,786 ± 4,561 vs. -249 ± 2,478, p<0.0005). Only 44% of patients with CAD and T2DM responded to clopidogrel as per VerifyNow® (cut-off PRUz value of ≥ 240). Importantly, no correlation was observed between thrombus area and VerifyNow® values (rho 0.08, p=0.49). Thrombus area values were similar among hypo-responders and good responders to clopidogrel (mean thrombus area ± SD: 12,186 ± 4,294 vs. 10,438 ± 3,401; p=0.17). Type 2 diabetes mellitus is associated with an increased blood thrombogenicity among NSTE-ACS patients on currently recommended medical therapy. Thrombus area was significantly reduced in all stable CAD patients independently of their response to clopidogrel therapy.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Girish N
authors.initials: GN
authors.lastname: Viswanathan
authors.forename: Sally M
authors.initials: SM
authors.lastname: Marshall
authors.forename: Clyde B
authors.initials: CB
authors.lastname: Schechter
authors.forename: Karthik
authors.initials: K
authors.lastname: Balasubramaniam
authors.forename: José J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: Azfar G
authors.initials: AG
authors.lastname: Zaman
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000368:Aged; D060050:Angina, Stable / Q000150:complications / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin