Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention

Thromb Res. 2018 Nov;171:38-44. doi: 10.1016/j.thromres.2018.09.046. Epub 2018 Sep 13.

Abstract

Background: It remains unknown if bivalirudin compared to heparin confers any additional inhibition of platelet and coagulation activation during primary percutaneous coronary intervention (PPCI) after pretreatment with ticagrelor.

Methods: In this substudy of VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor were randomized before PPCI to heparin or bivalirudin. Blood samples were collected before and 1 and 12 h after PPCI. We measured platelet reactivity (PR) using Multiplate, soluble P-selectin, thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2) as markers of platelet and coagulation activation.

Results: The median (IQR) time from ticagrelor administration to randomization was 63 (29) vs 60 (24) minutes, p = 0.28. ADP-induced PR did not significantly differ between groups over time (heparin vs bivalirudin, AUC 73 (62) vs 74 (68), p = 0.74, 32 (42) vs 43 (51), p = 0.38, 15 (15) vs 19 (15), p = 0.29, before, 1 and 12 h after PPCI). Soluble P-selectin did not significantly differ between groups. At 1 h TAT significantly increased with bivalirudin (3.0 (1.3) to 4.3 (4.2) ug/L; p < 0.01), but not with UFH (3.1 (2.1) to 3.5 (1.6) ug/L, p = 0.24). F1 + 2 increased in both groups but the rise was numerically higher with bivalirudin (170 (85) to 213 (126) pmol/L vs 168 (118) to 191 (103) pmol/L). At 12 h, a comparable significant increase in thrombin generation was observed in both groups.

Conclusion: In patients treated with ticagrelor, we found no major differences between bivalirudin and heparin in platelet aggregation or coagulation markers, which is in agreement with the neutral clinical results of the VALIDATE-SWEDEHEART study.

Keywords: Aggregation; Bivalirudin; Coagulation; Heparin; Platelet; Thrombin.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Anticoagulants / therapeutic use*
  • Antithrombins / therapeutic use
  • Blood Coagulation / drug effects*
  • Blood Platelets / drug effects
  • Female
  • Heparin / therapeutic use
  • Hirudins
  • Humans
  • Male
  • Peptide Fragments / therapeutic use*
  • Percutaneous Coronary Intervention / adverse effects
  • Percutaneous Coronary Intervention / methods*
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ticagrelor / therapeutic use*

Substances

  • Anticoagulants
  • Antithrombins
  • Hirudins
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Recombinant Proteins
  • Heparin
  • Ticagrelor
  • bivalirudin