DOACs in AF with ACS and/or PCI

There has been debate about the optimal anticoagulation therapy in patients with AF in the setting of ACS or PCI, a population known to have increased risk of bleeding and ischaemic complications.49,50 Current ESC guidelines on myocardial revascularisation recommend either triple therapy with aspirin, antiplatelet medication clopidogrel (a platlet P2Y12 inhibitor) and an oral anticoagulant for at least one month (and up to six months in patients with greater ischaemic vs. bleeding risk) or dual therapy with antiplatelet and oral anticoagulant medications (in patients with greater bleeding vs. ischaemic risk).51 In contrast, guidance from the US recommends a single antiplatelet therapy (clopidogrel) in combination with an oral anticoagulant.49

There is at least agreement that in the absence of contraindications, a DOAC is preferred over a vitamin K antagonist.52 Indeed, the RE-DUAL PCI trial recently showed that in patients with and without ACS, dual therapy with 110 mg and 150 mg dabigatran reduced bleeding risks compared with warfarin therapy in patients with AF after PCI.53 The ENTRUST-AF PCI trial is also ongoing to compare the risk of bleeding complications after PCI treatment with the DOAC edoxaban vs. vitamin K antagonists plus dual antiplatelet therapy.54

While the strategy of dropping aspirin to reduce risk of bleeding complications in the presence of other anticoagulant drugs has recently emerged, it wasn’t known whether this would also be preferable in patients with AF and ACS and/or PCI until the recent AUGUSTUS study.18 AUGUSTUS was an open-label, randomised controlled trial to evaluate the safety of the DOAC apixaban vs. vitamin K antagonist and aspirin vs. aspirin placebo in this patient population.55

AUGUSTUS included 4,614 patients from 33 countries with AF who had a recent ACS and/or underwent PCI, all of them on an antiplatelet medication with a six month follow up. The primary (safety) outcome was major bleeding and secondary outcomes included death or hospitalisation and a composite of ischaemic events. The protocol allowed two hypotheses to be investigated:

  • Whether the DOAC apixaban (5 mg or 2.5 mg twice daily) was non-inferior or superior to vitamin K antagonist at reducing bleeding events
  • Whether aspirin was inferior to placebo for reducing bleeding in patients on DOAC treatment

Primary outcomes:

  • In the anticoagulant-regimen comparison, a bleeding event was observed in 10.5% of patients treated with apixaban, compared with 14.7% of patients receiving a vitamin K antagonist, resulting in an event rate per 100 patient-years significantly lower among patients receiving apixaban (HR 0.69; 95% [CI], 0.58 to 0.81) - this met the criteria for both non inferiority and superiority (p<0.001)
  • In the antiplatelet-regimen comparison, a bleeding event was observed in 16.1% of patients receiving aspirin, compared with 9.0% of patients receiving placebo (HR 1.89; 95% CI, 1.59 to 2.24; p<0.001)

Secondary outcomes:

  • Patients in the apixaban group had a lower incidence of death or hospitalisation than those in the vitamin K antagonist group: 23.5% vs. 27.4% (HR 0.83; 95% CI, 0.74 to 0.93; p=0.002), but no difference in death or hospitalisation at 6 months was noted between patients receiving aspirin and those receiving placebo
  • At 6 months, there were no differences with regards to death or ischaemic events (myocardial infarction, definite or probable stent thrombosis, stroke, or urgent revascularisation) in the apixaban or vitamin K antagonist groups (154 vs. 163 events, respectively) or in the aspirin or placebo groups (149 vs. 168 events, respectively)

The authors concluded that in this patient population, an antithrombotic treatment regime that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalisations.55 Further, a meta-analysis of four trials of antithrombotic treatment in patients with AF, ACS and/or PCI (including AUGUSTUS) confirmed that a regimen of a DOAC plus antiplatelet medication was associated with less bleeding compared with vitamin K antagonists plus dual antiplatelet therapy and that omitting aspirin caused less bleeding.56

If you want to learn more about the pivotal AUGUSTUS trial, then make sure to come back to the Learning Zone after the European Society of Cardiology 2019 Congress. Professor Renato Lopes, the Principal Investigator of the AUGUSTUS study will give his insights on the trial and what it means for future clinical practice.

Review the European and American guidelines for anticoagulation use in atrial fibrillation


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