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Hemostatic effects ...
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Pehrsson, S.AstraZeneca AB
(författare)
Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
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LIBRIS-ID:oai:research.chalmers.se:1967552e-87d1-4bc6-9697-490456464123
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https://research.chalmers.se/publication/250705URI
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https://doi.org/10.1111/jth.13680DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Background: Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective: To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods: Pigs, pretreated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results: MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: bodyweight- adjusted blood loss in the 15-to 90-min interval, 12 (confidence interval [ CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg(-1) (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.1350.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.030.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94136) mmHg (aspirin alone). Conclusion: MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADPinduced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Johansson, K. J.AstraZeneca AB
(författare)
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Janefeldt, A.AstraZeneca AB
(författare)
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Sandinge, A. S.AstraZeneca AB
(författare)
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Maqbool, S.
(författare)
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Goodman, J.
(författare)
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Sanchez, J.AstraZeneca AB
(författare)
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Almqvist, Joachim E,1980Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)f00joal
(författare)
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Gennemark, Peter,1974AstraZeneca AB(Swepub:cth)peterg
(författare)
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Nylander, S.AstraZeneca AB
(författare)
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AstraZeneca ABChalmers tekniska högskola
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Thrombosis and Haemostasis: Elsevier BV15:6, s. 1213-12221538-78361538-7933
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Pehrsson, S.
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Johansson, K. J.
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Janefeldt, A.
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Sandinge, A. S.
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Maqbool, S.
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Goodman, J.
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visa fler...
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Sanchez, J.
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Almqvist, Joachi ...
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Gennemark, Peter ...
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Nylander, S.
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