What were the main achievements of Augustus


What to do in anticoagulated patients with atrial fibrillation who develop acute coronary syndrome or who require percutaneous coronary intervention (PCI)? A new analysis of the AUGUSTUS study is once again a plea for dual antithrombotic therapy.

The AUGUSTUS study is - after RE-DUAL PCI (dabigatran), ENTRUST-AF PCI (edoxaban) and PIONEER AF-PCI (rivaroxaban) - the fourth study, the direct oral anticoagulants (DOAK), in this case apixaban, in one Has examined a setting in which the patient has both atrial fibrillation and coronary heart disease. The crucial question in these patients is how intensive the antithrombotic therapy should be if an acute coronary syndrome (ACS) or elective PCI would formally require dual platelet inhibition.

In the AUGUSTUS study this was examined in a 4 × 4 factorial design. Because of the atrial fibrillation, the patients were randomized to take either vitamin K antagonists (VKA, target INR 2-3) or apixaban (2 × 5 mg or 2 × 2.5 mg). They all received a P2Y12 inhibitor in the usual dose in connection with the ACS or the elective PCI. After another randomization, either ASA (“triple therapy”) or placebo (“dual therapy”) was given. The duration of therapy for the combined anticoagulation was six months for all patients.

The AUGUSTUS main results had already been published in March, showing that dual therapy is superior to triple therapy in the case of apixaban too.

Dual regimes are ahead in all subgroups

A detailed subgroup analysis has now been carried out in San Francisco by Dr. Stephan Windecker from the University Hospital Bern presented. AUGUSTUS was the first such study in which a large subgroup of patients took part who were only treated with medication after ACS.

A total of 4,614 patients took part in the study, a good 1,000 of them with only drug-treated ACS, a good 1,700 with ACS and PCI and a further 1,700 with elective PCI. The short version is that the patients in all three subgroups benefit similarly from the dual therapy on the one hand and from the DOAC on the other hand with regard to bleeding and with regard to death or hospitalization.

Severe bleeding according to ISTH or clinically relevant, non-severe bleeding were 56% and 32% less frequent in the drug-treated ACS patients and in the ACS patients treated via PCI with dual therapy. That was statistically significant. Bleeding was also 18% less common in elective PCI patients, but the difference was not significant.

Death or hospitalization was a significant 29% less common in ACS patients on drug treatment and dual therapy. With ACS and PCI therapy it was not a significant 12% and with elective PCI it was not a significant 13%.

Apixaban with advantages over VKA

The direct comparison between apixaban and VKA, which is also possible through the factorial design, was similarly consistent across the three subgroups and was mostly in favor of apixaban. Death or hospital admissions occurred in the apixaban groups with an incidence of 17.7% (ACS treated with medication), 26.2% (ACS patients treated with PCI) and 24.5% (elective PCI). For VKA therapy, the corresponding incidence rates were 24.4%, 28.8% and 27.6%.

Serious or clinically relevant bleeding was observed in 5.3%, 10.7% and 13.7% of the patients under apixaban therapy and in 11.5% / 15.0% / 16.3% of the patients under VKA therapy . There was no significant or greater numerical advantage when death and ischemic events were evaluated together. This already applied to the overall analysis, and it also applies to the three subgroups.

Short-term triple therapy might be necessary - just for how long?

Overall, there are clear advantages for the NOAC-based regimes on the one hand, and clear advantages for the dual in comparison to the triple regimes on the other. However, this is not entirely true: With ASA therapy there were numerically fewer stent thromboses than placebo - half as many - and about a fifth fewer myocardial infarctions.

That wasn't significant, but it could be the price to be paid for the higher bleeding safety with the dual regimen. Against this background, it was discussed in San Francisco to what extent PCI patients should be given short-term triple therapy and, if so, what a reasonable period of time could be. There is currently no answer to this question. However, another AUGUSTUS evaluation will follow, which will focus on stent thrombosis.