Key result
Unfractionated heparin inhibited thrombin-inducible cleavage of PAR-1 more effectively than bivalirudin in blood samples from patients undergoing elective PCI.
Why the study?
Does unfractionated heparin compared to bivalirudin affect thrombin-inducible platelet PAR-1 cleavage and internalization in patients undergoing elective PCI?
RCT (n=89)
randomly assigned
Does unfractionated heparin compared to bivalirudin affect thrombin-inducible platelet PAR-1 cleavage and internalization in patients undergoing elective PCI?
Heparin has stronger inhibitory effects on thrombin-dependent PAR-1 cleavage and internalization than bivalirudin, providing a mechanistic explanation for the lower bleeding rates observed with bivalirudin in PCI.
Answers are grounded in this paper and cite their sources.
Bivalirudin may reduce bleeding versus heparin in elective PCI via weaker PAR-1 inhibition; extends mechanistic understanding of anticoagulant effects.
Aims We examined the specific effects of unfractionated heparin and bivalirudin on thrombin-inducible platelet PAR-1 in patients undergoing percutaneous coronary intervention (PCI). Methods and results To simulate in vivo conditions that may precipitate a bleeding event, we added thrombin in vitro to blood samples from 89 patients who had been randomly assigned to receive heparin or bivalirudin for elective PCI and examined thrombin-inducible PAR-1 expression. Thrombin-inducible cleavage of PAR-1 was inhibited by heparin, but not affected by bivalirudin (P = 0.0001). Further, PAR-1 internalization was more effectively inhibited by heparin than bivalirudin (P = 0.002). Conclusion Heparin has stronger inhibitory effects on thrombin-dependent PAR-1 cleavage and internalization, thus providing a biological explanation for lower clinical bleeding rates with bivalirudin.
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Eslam et al. (2009) conducted an RCT in percutaneous coronary intervention (PCI) (n=89). Unfractionated heparin vs. Bivalirudin was evaluated on Thrombin-inducible cleavage of PAR-1 (p=0.0001). Unfractionated heparin inhibited thrombin-inducible cleavage of PAR-1 more effectively than bivalirudin in blood samples from patients undergoing elective PCI.
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