Selective inhibition of factor Xa is more efficient than factor VIIa-tissue factor complex blockade at facilitating coronary thrombolysis in the canine model

Journal of the American College of Cardiology
J LefkovitsF A Nicolini

Abstract

We determined the effect of adjunctive inhibition of the extrinsic coagulation pathway by factor VIIa-tissue factor complex inhibitors, DEGR VIIa and tissue factor pathway inhibitor (TFPI), and the selective factor Xa inhibitor, tick anticoagulant peptide (TAP), after thrombolytic therapy with tissue-type plasminogen activator (t-PA) in a canine model of electrically induced coronary thrombosis. Ongoing thrombin generation is considered an important component of the heightened thrombin activity associated with thrombolytic therapy and may be responsible for reperfusion failure and reocclusion. Forty-two dogs with electrically induced coronary thrombus undergoing thrombolysis with t-PA (1 mg/kg over 20 min) were randomly assigned to one of the following adjunctive regimens: TAP (30 micrograms/kg body weight per min for 90 min, n = 10); TFPI (100 to 150 micrograms/kg per min for 90 min, n = 10); DEGR VIIa (1- to 2-mg/kg bolus, n = 10) and saline control (n = 12). The dogs were observed for 120 min after thrombolysis for reocclusion. All three active study agents accelerated the time to reperfusion by an average of 12 min (all p < 0.05). Duration of reflow was greatest with TAP (117 +/- 8 min, p < 0.05 compared with saline control...Continue Reading

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Citations

Dec 18, 2010·Nature Reviews. Drug Discovery·Elisabeth PerzbornFrank Misselwitz
Jun 12, 2010·Thrombosis and Haemostasis·A Phillip Owens, Nigel Mackman
Jan 11, 2001·Journal of Pharmacological and Toxicological Methods·R J LeadleyA Gagnon
Mar 26, 2011·Annals of the New York Academy of Sciences·Frank MisselwitzElisabeth Perzborn
Jul 5, 2005·Expert Opinion on Investigational Drugs·B KaiserJ Fareed
Jul 2, 2005·Expert Opinion on Investigational Drugs·L ChiK P Gallagher
Oct 2, 2012·Circulation Research·Calvin H YehJeffrey I Weitz
Dec 22, 1999·Journal of Cardiovascular Pharmacology·R J LeadleyC T Dunwiddie

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