Anticoagulants and Primary PCI

Jafary, Fahim H.

doi:10.1007/978-981-13-1114-7_9

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…injection of 0.75 mg/kg, followed by a 1.75 mg/kg/h continuous i.v. infusion, with a short half-life of 25 min [ 44 ]. Our study suggests that rFasxiator N17R, L19E is likely to have a slightly longer duration of action (between 60 min and 90 min) when administered i.v., which is consistent with the short half-life of other low-molecular-weight proteins and peptides [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis

Chng

Lim

et al. 2022

Biomedicines

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Activated factor XI (FXIa) is an important antithrombotic drug target. Clinical and pre-clinical data have demonstrated that its inhibition attenuates thrombosis with minimal risk of excessive bleeding. We isolated Fasxiator from the venom of banded krait Bungarus fasciatus and subsequently engineered FasxiatorN17R,L19E, with improved affinity (Ki = 0.9 nM) and selectivity towards FXIa. Here, we assess the in vivo efficacy and bleeding risk of rFasxiatorN17R, L19E in pre-clinical animal models. Rats injected intravenously (i.v.) with bolus rFasxiatorN17R, L19E showed the specific in vivo attenuation of the intrinsic coagulation pathway, lasting for at least 60 min. We performed the in vivo dose-ranging experiments for rFasxiatorN17R, L19E as follows: FeCl3-induced carotid artery occlusion in rats (arterial thrombosis); inferior vena cava ligation in mice (venous thrombosis); tail bleeding time in both rats and mice (bleeding risk). Head-to-head comparisons were made using therapeutic dosages of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for arterial and venous thrombosis, respectively. In the arterial thrombosis model, 2 mg/kg i.v. rFasxiatorN17R,L19E achieved a similar antithrombotic efficacy to that of UFH, with >3-fold lower bleeding time. In the venous thrombosis model, the 10 mg/kg subcutaneous (s.c.) injection of rFasxiatorN17R,L19E achieved similar efficacy and bleeding levels to those of LMWH enoxaparin. Overall, rFasxiatorN17R,L19E represents a promising molecule for the development of FXIa-targeting anticoagulants.

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Section: Discussionmentioning

confidence: 99%

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis

Chng

Lim

et al. 2022

Biomedicines

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“…Reperfusion therapy, preferably by primary percutaneous intervention (PPCI) is recommended therapy for STEMI by the American Heart Association/American College of Cardiology (AHA/ACC) [4] as well as the European Society of Cardiology (ESC) [2] if it can be performed in a timely fashion within 12 h of onset of STEMI. However, PPCI itself increases thrombogenic potential due to the use of thrombogenic catheters and wire, balloon-induced coronary endothelial disruption resulting in activation of platelet and coagulation system, as well as due to the thrombogenic potential of stents [5]. Therefore, anticoagulation during the peri-PCI period for STEMI is vital not only to hinder clot progression in plaque-ruptured vessels but also for the prevention of adverse thrombotic complications of PPCI [5] [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, PPCI itself increases thrombogenic potential due to the use of thrombogenic catheters and wire, balloon-induced coronary endothelial disruption resulting in activation of platelet and coagulation system, as well as due to the thrombogenic potential of stents [5]. Therefore, anticoagulation during the peri-PCI period for STEMI is vital not only to hinder clot progression in plaque-ruptured vessels but also for the prevention of adverse thrombotic complications of PPCI [5] [6]. For antithrombosis during peri-PCI, AHA/ ACC along with Society for Cardiovascular Angiography & Interventions (SCAI) jointly recommended unfractionated heparin (UFH) as a class I recommendation anti-thrombotic agent, mainly to reduce ischemic events with bivalirudin as class I agent in presence of heparin-induced thrombocytopenia or class 2b agent alternate to UFH to reduce bleeding [7] and the same kind recommendations were made by ESC [2].…”

Section: Introductionmentioning

confidence: 99%

Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis

Oli,

Shrestha,

Shtembari

et al. 2023

Coronary Artery Disease

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Background The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population. Methods This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. Results Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61–0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74–0.98), any bleeding (OR 0.61, CI 0.45–0.83), major bleeding (OR 0.54, CI 0.39–0.75), all-cause mortality (OR 0.79, CI 0.67–0.92) and cardiac mortality (OR 0.78, CI 0.65–0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52–1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62–2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69–6.09) significantly at 30 days. Conclusion Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.

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Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis

Mushahid,

Shah,

Farhan

et al. 2024

Am J Cardiovasc Drugs

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Anticoagulants and Primary PCI

Cited by 4 publications

References 17 publications

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis

A Factor XIa Inhibitor Engineered from Banded Krait Venom Toxin: Efficacy and Safety in Rodent Models of Arterial and Venous Thrombosis

Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis

Differential Use of Glycoprotein IIb/IIIa Inhibitors with Bivalirudin in Patients with STEMI Undergoing PCI: A Systematic Review and Meta-Analysis

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