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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.
AUGUSTUS Clinical Trial
To determine in patients with NVAF on antiplatelet therapy with a P2Y12 inhibitor for 6 months, after a recent ACS and / or PCI:1
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
Exclusion criteria:1
The 2 x 2 factorial design allowed for the evaluation of two independent study hypotheses:1
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
Secondary efficacy endpoints1
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
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
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