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• A role for universal use of low-dose edoxaban in triple antithrombotic therapy
  oscar,m Jolobe
  Published on: 6 December 2018

• Published on: 6 December 2018

  A role for universal use of low-dose edoxaban in triple antithrombotic therapy

  • oscar,m Jolobe, retired geriatrician manchester medical society

  The recommendation that combined antiplatelet and new oral anticoagulant(NOAC) therapy should rely on the lowest approved NOAC dose effective for stroke prevention(1) is one which favours low-dose edoxaban instead of either dabigatran, rivaroxaban, or apixaban, when reduction of risk of gastrointestinal(GIT) bleeding is taken into account. In a review of clinical experience of bleeding associated with NOACs(dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in nonvalvular atrial fibrillation(NVAF), edoxaban 30 mg/day was the only antithrombotic agent associated with significantly(p < 0.001) lower risk of GIT bleeding than warfarin(Hazard Ratio: 0.67;95% Confidence Interval 0.53 to 0.83). For apixaban and for dabigatran 110 mg BID, the risk of GIT bleeding was comparable with the risk associated with warfarin use. For rivaroxaban and for dabigatran 150 mg BID the risk of GIT haemorrhage was significantly higher(P < 0.0001, and p < 0.001, respectively) than the GIT bleeding risk associated with warfarin(2).
  In a study where 92.2% of 5301 NVAF users of antiplatelet agents were prescribed a NOAC in combination with only one antiplatelet agent vs 86.3% of 9106 NVAF users of antiplatelet agents who were prescribed warfarin with only one antiplatelet agent , concomitant antiplatelet and NOAC use was associated with significantly lower risk of intracranial bleeding than concomitant antiplatelet and warfarin use(HR 0.68, 95% CI, 0.51 to 0.91). Ne...

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  The recommendation that combined antiplatelet and new oral anticoagulant(NOAC) therapy should rely on the lowest approved NOAC dose effective for stroke prevention(1) is one which favours low-dose edoxaban instead of either dabigatran, rivaroxaban, or apixaban, when reduction of risk of gastrointestinal(GIT) bleeding is taken into account. In a review of clinical experience of bleeding associated with NOACs(dabigatran, rivaroxaban, apixaban, and edoxaban) versus warfarin in nonvalvular atrial fibrillation(NVAF), edoxaban 30 mg/day was the only antithrombotic agent associated with significantly(p < 0.001) lower risk of GIT bleeding than warfarin(Hazard Ratio: 0.67;95% Confidence Interval 0.53 to 0.83). For apixaban and for dabigatran 110 mg BID, the risk of GIT bleeding was comparable with the risk associated with warfarin use. For rivaroxaban and for dabigatran 150 mg BID the risk of GIT haemorrhage was significantly higher(P < 0.0001, and p < 0.001, respectively) than the GIT bleeding risk associated with warfarin(2).
  In a study where 92.2% of 5301 NVAF users of antiplatelet agents were prescribed a NOAC in combination with only one antiplatelet agent vs 86.3% of 9106 NVAF users of antiplatelet agents who were prescribed warfarin with only one antiplatelet agent , concomitant antiplatelet and NOAC use was associated with significantly lower risk of intracranial bleeding than concomitant antiplatelet and warfarin use(HR 0.68, 95% CI, 0.51 to 0.91). Nevertheless, risk of GIT bleeding was comparable(HR 1,08, 95% CI, 0.81 to 1.45)(3).
  Given the fact that VKA therapy is associated with greater risk of intracranial bleeding than NOAC therapy, not only in the absence of concomitant antiplatelet drug use(2), but also in the context of combined anticoagulant and only one antiplatelet agent (3), the safest use of triple antithrombotic therapy(TAT) appears to be one which involves either low-dose edoxaban, low-dose dabigatran or apixaban so as to optimise mitigation of the risk of gastrointestinal bleeding..
  Although PIONEER AF-PCI was a TAT study which documented significantly(p < 0.001) lower rates of clinically significant bleeding in recipients of TAT involving low dose rivaroxaban than in recipients of TA involving warfarin that study was not powered to evaluate non inferiority of the low-dose rivaroxaban regime to the warfarin regime for thromboprophylaxis against NVAF-related stroke(4). Future trials should now optimise the advantage that the sole use of low-dose edoxaban enjoys over sole use of other NOACs in mitigating the risk of both intracranial and GIT bleeding, by exploring the possibility that the universal inclusion of the 30 mg/day edoxaban dose (irrespective of renal function and body weight), in a TAT regime might be non inferior to a TAT regime that involves warfarin, with regard to thromboprophylaxis against NVAF-related stroke. .
  I have no funding and no conflict of interest
  References
  (1) Capodano D
  Triple antithrombotic therapy after ACS and PCI in patients on chronic oral anticoagulation Update
  Heart 2018;104:1976-1983
  (2) Eikelboom J., Meril G
  Bleeding with direct oral anticoagulants vs warfarin: Clinical experience
  Am J Med 2016;129:S33-S40
  (3)Douros A., Renoux X., Yin H et al
  Concomitant use of direct oral anticoagulants with antiplatelet agents and the risk of major bleeding in patients with nonvalvular atrial fibrillation
  Am J Med 2018;DOI.org/10.1016/amjmed 2018.10.008
  (4) Gibson CM., Mehran R., Bode C et al
  Prevention of bleeding in patients with atrial fibrillation undergoing PCI
  N Engl J Med 2016;375:2423-2434

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  Conflict of Interest:
  None declared.

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