Ischemic outcomes with antithrombotic regimes in AF patients with ACS or undergoing PCI
Revisiting the effects of omitting aspirin in combined antithrombotic therapies for atrial fibrillation and acute coronary syndromes or percutaneous coronary interventions: meta-analysis of pooled data from the PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS trials.
Introduction and methods
Guidelines recommend triple antithrombotic therapy (TAT), consisting of an oral anticoagulant (OAC) and two antiplatelet agents (aspirin and a P2Y12 inhibitor) in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). TAT has been associated with increased risk of major bleeding , and an alternative therapy with reduced risk of bleeding is dual antithrombotic therapy (DAT), including an OAC and P2Y12 inhibitor.
RE-DUAL PCI  and PIONEER AF-PCI  demonstrated that a regimen of a NOAC (dabigatran and rivaroxaban, respectively) combined with a P2Y12 inhibitor (mostly clopidogrel) without aspirin resulted in reduced bleeding than TAT regimens with a VKA. In patients on a P2Y12 inhibitor, therapy regimens without aspirin and with apixaban showed less bleeding than regimens including aspirin, a VKA or both, as demonstrated in the AUGTUSTUS trial .
These three recent trials were not powered to detect differences of DAT or NOAC-based regimens in ischemic endpoints in comparison with TAT or VKA-based regiments and it is therefore questionable whether these regimens give optimal reduction of ischemic events in AF patients with ACS or PCI.
A meta-analysis of PIONEER AF-PCI, RE-DUAL PCI and AUGUSTUS including 9463 patients was conducted to compare DAT with TAT regimens and NOAC-based regimens with VKA-based therapies in AF patients with ACS or undergoing PCI.
DAT (no aspirin) vs TAT (with aspirin)
- Bleeding risk was lower with DAT regimens compared to TAT regimens
- There was no difference in the risk of ischemic stroke between DAT and TAT regimens (OR: 1.010, 95% CI 0.675–1.512; P=0.962).
- There was no increased risk of MI with DAT regimens compared to TAT (OR: 1.211, 95% CI:0.955–1.535; P=0.115).
- Analysis of risk of stent thrombosis leaving out AUGUSTUS patients who were medically managed showed that DAT regimens resulted in a higher risk compared to TAT (OR 1.672, 95%CI: 1.022–2.733, P=0.041).
- There was no increased risk of pooled ischemic events with DAT compared to TAT regimens.
- No difference was observed for all-cause mortality between DAT and TAT regimens (data available from RE-DUAL PCI and AUGUSTUS trial), nor for CV mortality (PIONEER AF-PCI and AUGUSTUS).
NOAC vs VKA
- NOAC-based regimens were associated with lower bleeding risk compared to VKA-based therapies.
- Risk of ischemic stroke was not different for NOAC and VKA regimens (OR 0.844, 95% CI 0.557–1.281; P = 0.426).
- Risk of MI was similar with NOAC-based therapies and VKA-based regimens (OR 0.984, 95% CI: 0.777–1.246; P=0.895).
- There was no difference in risk of stent thrombosis between NOAC-based treatments and VKA-based regimens (OR: 1.095, 95% CI:0.676–1.773, P=0.713).
- There was no significant difference in the risk of pooled ischemic events between the NOAC and VKA regimens.
- No differences were observed for all-cause mortality and CV mortality between NOAC-based and VKA-based regimens.
This meta-analysis of three trials including AF patients with ACS or undergoing PCI showed that 1) NOAC-based treatments were associated with less bleeding and similar risk for ischemic events and all-cause and CV mortality compared to VKA-based therapies and 2) DAT regimes compared to TAT were associated with reduced bleeding, similar risk of ischemic stroke, MI, pooled ischemic events, all-cause and CV mortality, but increased risk of stent thrombosis.
Future studies may provide answers on the timing of aspirin withdrawal and use of other P2Y12 inhibitors in combination with OAC.