Direct oral anticoagulants in addition to antiplatelet therapy for secondary prevention after acute coronary syndromes

Selected in JAMA Cardiology by D. Milasinovic



Chiarito M., Cao D., Cannata F., Godino C., Lodigiani C., Ferrante G., Lopes RD., Alexander JH., Reimers B., Condorelli G., Stefanini GG.


JAMA Cardiol. 2018 Feb 7 [Epub ahead of print]


February 2018


Read the abstract

My Comment

Why this study – the rationale/objective?

Although antiplatelets are the current mainstay of secondary prevention after acute coronary syndromes (ACS), the addition of direct oral anticoagulants (DOACs) to antiplatelet therapy (APT) has shown potential to improve outcomes. This study aimed at investigating a possible differential effect of DOACs in patients with vs. without ST-elevation ACS (STEMI vs. NSTE-ACS).

How was it executed – the methodology?

  • Pooled analysis of 6 randomized trials including 29 667 patients with ACS (14 580 STEMI and 15 036 NSTE-ACS), who were randomized to either a DOAC or placebo, in addition to APT.
  • Primary efficacy endpoint was cardiovascular death, myocardial infarction (MI) or stroke, and primary safety endpoint was major bleeding, during 6-13 months of follow-up.

What is the main result?

  • In the overall population, DOACs reduced the risk of ischemic events (OR 0.85, p<0.001), but increased major bleeding (OR 3.17, p<0.001).
  • Importantly, DOACs reduced ischemic events in patients with STEMI (OR 0.76, p<0.001), but not in those with NSTE-ACS (OR 0.92, p=0.36), whereas bleeding was consistently increased in both subgroups.
  • Regarding individual endpoints, DOACs were associated with a tendency to reduce cardiovascular death and a significantly lower MI rate, in the overall population and in the STEMI subgroup, but not in the NSTE-ACS subgroup. Stroke occurred at a similar rate in all patient groups.

Critical reading and the relevance for clinical practice

This meta-analysis has at least two important messages. First, it reiterates previous findings of a reduction in ischemic events, when DOAC is added to an antiplatelet agent, albeit at a cost of more bleeding. Second, DOACs in STEMI are associated with a more favorable risk-benefit ratio (bleeding vs. ischemic complications), as compared with NSTE-ACS.

However, these conclusions and their clinical applicability need to be taken with caution, due to known limitations of a study-level meta-analysis. More specifically, the pooled trials here differed in two crucial respects. First, different DOACs were used (apixaban, rivaroxaban, dabigatran) and in varying doses. Second, the definition of major bleeding was not uniform among the included trials, which makes the interpretation of data pooling for this event difficult. These limitations notwithstanding and pending a detailed analysis of the type of bleeding and their impact on mortality, the present pooled-analysis seems to be aligned with the recently published COMPASS trial, which showed that adding low-dose rivaroxaban (2.5mg twice daily) to aspirin may improve prognosis in patients with stable coronary artery disease.

As noted in a recent EuroIntervention editorial (Oral antithrombotic therapy after acute coronary syndromes: "dual antiplatelet" or "dual pathway"? EuroIntervention. 2017 Sep 20;13(7):773-775), the use of DOACs in addition to an antiplatelet agent may provide incremental benefit by allowing for a “dual pathway” effect, i.e. targeting both platelets and the coagulation cascade.

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