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

Venetsanos, Dimitrios; Lindahl, Tomas L.; Lawesson, Sofia Sederholm; Gustafsson, Kerstin M.; Wallen, Håkan; Erlinge, David LU ; Swahn, Eva and Alfredsson, Joakim (2018) In Thrombosis Research 171. p.38-44
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aggregation, Bivalirudin, Coagulation, Heparin, Platelet, Thrombin
in
Thrombosis Research
volume
171
pages
7 pages
publisher
Elsevier Ltd
external identifiers
  • scopus:85053795837
ISSN
0049-3848
DOI
10.1016/j.thromres.2018.09.046
language
English
LU publication?
yes
id
37ae882e-8844-4c9b-bfb5-ae7ccfcb9076
date added to LUP
2018-10-09 09:30:10
date last changed
2019-02-20 11:30:10
@article{37ae882e-8844-4c9b-bfb5-ae7ccfcb9076,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Venetsanos, Dimitrios and Lindahl, Tomas L. and Lawesson, Sofia Sederholm and Gustafsson, Kerstin M. and Wallen, Håkan and Erlinge, David and Swahn, Eva and Alfredsson, Joakim},
  issn         = {0049-3848},
  keyword      = {Aggregation,Bivalirudin,Coagulation,Heparin,Platelet,Thrombin},
  language     = {eng},
  pages        = {38--44},
  publisher    = {Elsevier Ltd},
  series       = {Thrombosis Research},
  title        = {Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention},
  url          = {http://dx.doi.org/10.1016/j.thromres.2018.09.046},
  volume       = {171},
  year         = {2018},
}