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ELIQUIS® (apixaban) is indicated for prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (NVAF), with one or more risk factors, such as prior stroke or transient ischaemic attack (TIA), age ≥75 years, hypertension, diabetes mellitus, symptomatic heart failure (NYHA Class ≥II); treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults; and, prevention of venous thromboembolic events (VTE) in patients who have undergone elective hip or knee replacement surgery.

What’s new

AUGUSTUS Clinical Trial

In the AUGUSTUS clinical trial, ELIQUIS® demonstrated superiority over VKA for major or CRNM bleeding in patients with NVAF who had a recent ACS and / or PCI1,2*

There is limited experience of treatment with ELIQUIS at the recommended dose for NVAF patients when used in combination with antiplatelet agents in patients with ACS and / or undergoing PCI after haemostasis is achieved.2

Discover the data on the safety outcomes of ELIQUIS in patients with NVAF after a recent ACS and / or PCI

Watch the video below to learn how the AUGUSTUS trial may support your treatment decisions in patients with NVAF after a recent ACS and / or PCI1

This is a promotional video developed and funded by the BMS / Pfizer Alliance.

To determine in patients with NVAF on antiplatelet therapy with a P2Y12 inhibitor for 6 months, after a recent ACS and / or PCI:1

  • whether ELIQUIS is non-inferior and possibly superior to VKA (INR target range 2.0−3.0) for the combined outcome of ISTH major† and CRNM‡ bleeding
  • whether an OAC plus single antiplatelet therapy (P2Y12 inhibitor) is superior to an OAC plus dual antiplatelet therapy (P2Y12 inhibitor + aspirin) for the combined outcome of ISTH major and CRNM bleeding

Patients with NVAF were randomised within 14 days of ACS and / or PCI and, by using a 2 x 2 factorial study design, investigators were able to test two interventions in one patient population.1

Inclusion criteria:1

  • Age ≥18 years
  • Diagnosis of AF
  • Planned long-term OAC use
  • Recent ACS or PCI
  • Planned P2Y12 inhibitor use for ≥6 months

Exclusion criteria:1

  • Use of an anticoagulant for other conditions
  • Severe renal insufficiency
  • History of intracranial haemorrhage
  • Recent / planned coronary-artery bypass graft surgery
  • Coagulopathy / ongoing bleeding
  • Contraindication to VKA, ELIQUIS, all P2Y12 inhibitors, or aspirin

The 2 x 2 factorial design allowed for the evaluation of two independent study hypotheses:1

  1. Non-inferiority of ELIQUIS and possibly superiority vs. VKA, each in combination with a P2Y12 inhibitor with / without aspirin for the outcome of ISTH major or CRNM bleeding
  2. Superiority of single antiplatelet therapy with a P2Y12 inhibitor vs. dual antiplatelet therapy with a P2Y12 inhibitor and aspirin for the outcome of ISTH major or CRNM bleeding

The recommended dose of ELIQUIS 5 mg BD was used, unless the patient met two or more of the ABC dose-reduction criteria: (age ≥80 years, body weight ≤60 kg, creatinine ≥1.5 mg/dl [133 μmol/l]), in which case the reduced dose, ELIQUIS 2.5 mg BD, was used.1

Patients with severe renal impairment (CrCl 15–29 ml/min) alone should receive the ELIQUIS 2.5 mg BD reduced dose.2

ELIQUIS is not recommended in patients with CrCl <15 ml/min or in patients undergoing dialysis.2

At 6 months

Primary safety endpoint1

  • Major or clinically relevant non-major bleeding, as defined by the ISTH

Secondary efficacy endpoints1

  • Composite of death or hospitalisation
  • Composite of death or ischaemic events (stroke, myocardial infarction, definite / probable stent thrombosis or urgent revascularisation)

ELIQUIS vs. VKA: AUGUSTUS trial primary safety outcome

Event rate per 100 patient-years
24.7 with ELIQUIS (n=241) vs. 35.8 with VKA (n=332), HR=0.69 (95% CI: 0.58–0.81); p<0.001.1

  • For the primary safety endpoint, ELIQUIS showed overall superiority to VKA in the study population. For VKA, additional analyses using subgroups by TTR showed highest bleeding associated with the lowest quartile of TTR and similar bleeding rates in the highest quartile of TTR, vs. ELIQUIS2
  • ELIQUIS should be used with caution when co-administered with aspirin and / or P2Y12 inhibitors because these medicinal products typically increase the bleeding risk2
  • In patients with atrial fibrillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with ELIQUIS2

    • Refer to the ELIQUIS SmPC for further information.2

ELIQUIS vs. VKA: AUGUSTUS trial secondary efficacy outcomes

Event rate per 100 patient-years
57.2 with ELIQUIS (n=541) vs. 69.2 with VKA (n=632), HR=0.83 (95% CI: 0.74–0.93); p=0.002.1

Secondary efficacy outcome: composite of death or ischaemic events

There was no significant difference in the incidence of death or ischaemic events between ELIQUIS and VKA.1

Event rate per 100 patient-years
14.3 with ELIQUIS (n=154) vs. 15.3 with VKA (n=163), HR=0.93 (95% CI: 0.75–1.16); p=NS.1

Aspirin vs. placebo: AUGUSTUS trial primary safety outcome

Event rate per 100 patient-years
40.5 with aspirin (n=367) vs. 21.0 with placebo (n=204), HR=1.89 (95% CI: 1.59–2.24); p<0.001.1

Aspirin vs. placebo: AUGUSTUS trial secondary efficacy outcomes

Event rate per 100 patient-years
65.7 with aspirin (n=604) vs. 60.6 with placebo (n=569), HR=1.08 (95% CI: 0.96–1.21); p=NS.1

Secondary efficacy outcome: composite of death or ischaemic events

There was no significant difference in the incidence of death or ischaemic events between aspirin and placebo1

Event rate per 100 patient-years

13.9 with aspirin (n=149) vs. 15.7 with placebo (n=168), HR=0.89 (0.71–1.11); p=NT.1

The AUGUSTUS trial has two limitations:1,2

  • TTR for patients on VKA was modestly lower than in some RCTs for stroke prevention in patients with NVAF. For patients randomised to VKA, the proportion of TTR (INR 2–3) was 56%
  • This trial was not designed to be large enough to detect potentially clinically important differences in less common but important individual ischaemic outcomes

AUGUSTUS provides further data on the safety outcomes of ELIQUIS in patients with NVAF after a recent ACS and / or PCI1

FOOTNOTES

* The AUGUSTUS clinical trial was a two-by-two factorial, randomised, controlled clinical trial in 4,614 patients who had an ACS or had undergone PCI. Patients were randomly assigned to receive open-label ELIQUIS 5 mg BD (or 2.5 mg BD in selected patients [4.2%]) or a VKA and to receive double-blind aspirin (81 mg) or matching placebo OD.2 The primary safety endpoint for both factorial comparisons was major or CRNM bleeding as defined by the ISTH. Secondary endpoints included the composite of death or hospitalisation and the composite of death or ischaemic events (stroke, myocardial infarction, definite or probable stent thrombosis, or urgent revascularisation).1

† ISTH defined major bleeding as bleeding that resulted in death, occurred in a critical organ (intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, intramuscular with compartment syndrome, or pericardial), or was associated with either a decrease in the haemoglobin level of at least 2 g/dl or a transfusion of at least 2 units of packed red cells.1

‡ CRNM was defined as bleeding that resulted in hospitalisation, medical or surgical intervention for bleeding, an unscheduled clinic visit, or a change in physician-directed antithrombotic therapy.1

§ Aspirin was administered at a dose of 81 mg OD.1

ACS = Acute Coronary Syndrome   AF = Atrial Fibrillation   ARI = Absolute Risk Increase   ARR = Absolute Risk Reduction   BD = Twice Daily   
CI = Confidence Interval   
CRNM = Clinically Relevant Non-Major   HR = Hazard Ratio   INR = International Normalised Ratio   
ISTH = International Society on Thrombosis and Haemostasis   
NNH = Number Needed to Harm  NNT = Number Needed to Treat   NS = Not Significant   NSAID = Non-Steroidal Anti-Inflammatory Drug   NT = Not Tested   
NVAF = Non-Valvular Atrial Fibrillation   OAC = Oral Anticoagulant   OD = Once Daily   PCI = Percutaneous Coronary Intervention   P2Y12 = Purinergic signalling receptor Y12   SmPC = Summary of Product Characteristics   TTR = Time in Therapeutic Range   
VKA = Vitamin K Antagonist

REFERENCES

  1. Lopes RD et al. N Engl J Med 2019; 380: 1509–1524.
  2. ELIQUIS® (apixaban) Summary of Product Characteristics. Available at www.medicines.org.uk.