Abstract

Background
Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding.
Objective
We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis.
Methods
In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level.
Results
There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance.
Conclusion
Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis.
Condensed abstract
Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.
Original languageEnglish
Pages (from-to)144–154
Number of pages11
JournalThrombosis Research: Vascular Obstruction, Hemorrhage and Hemostasis
Volume236
Early online date3 Mar 2024
DOIs
Publication statusPublished - Apr 2024

Keywords

  • Humans
  • Platelet Aggregation Inhibitors/pharmacology
  • Rivaroxaban/pharmacology
  • Clopidogrel/therapeutic use
  • Fibrinolysis
  • Ticagrelor/therapeutic use
  • Acute Coronary Syndrome/drug therapy
  • Prospective Studies
  • Aspirin/pharmacology
  • Thrombosis

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