Eliquis in the Management of NVAF and VTE
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The statements, conclusions and opinions contained in the following
presentations are those of the presenter and do not necessarily reflect those
of the sponsor Bristol-Myers Squibb or Pfizer.
Please refer to the appropriate approved Product Information before prescribing
any agents mentioned in this presentation.
The Product Information is available through the BMS Australia and Pfizer
Australia websites, the trade display or from your BMS or Pfizer representative.
Bristol-Myers Squibb Australia Pty Ltd, ABN 33 004 333 322, Level 2, 4 Nexus Court, Mulgrave, VIC, Australia.
Pfizer Australia Pty Ltd, ABN 50 008 422 348 38-42 Wharf Road, West Ryde, NSW, AUSTRALIA. 432AU1700005-02. PP-ELI-AUS-0421
Approximately 90% of AF is non-valvular (NVAF)1,2
Valvular AF mainly refers to AF in the presence of:
•
rheumatic valvular disease (predominantly mitral stenosis) or
• mechanical heart valves3
AF associated with rheumatic heart disease and mechanical valves
require vitamin K antagonists
References: 1. Sansom L. Review of anticoagulation therapies in atrial fibrillation. 2012. 2. Deloitte Access Economics. September 2011. 3.
Kirchhoff P et al. Eur Heart J 2016; 37: 2893–962.
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NVAF in Australia
• Non-valvular atrial fibrillation is prevalent in 1–2% of Australians,
affecting 240,000–450,000 people1,2
• The incidence of AF increases with age – 1 in 20 people aged >70 years
is estimated to have NVAF3
• Up to 3 in 10 Australians with AF are undiagnosed2
• Patients with AF are five times more likely to have a stroke than those without AF3,4
References:
1. The economic costs of atrial fibrillation in Australia. PricewaterhouseCoopers, June 2010. 2. Off beat: Atrial fibrillation and the cost
of preventable strokes. Deloitte Access Economics, September 2011. 3 Wolf PA et al. Stroke 1991; 22: 983-8. 4. Granger CB et al.
Circulation 2012; 125: 159-64; discussion 64.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
AF-related Stroke in Australia
• It was estimated that 62,000 strokes would occur in Australia in 2011,
including 45,000 first-ever strokes1
– It is estimated that nearly one-third of first-ever strokes among the
Australian population (~14,000 strokes) occur in those with AF
– An estimated three-quarters of these (~10,000 strokes) can be specifically
attributed to patients’ AF rather than other clinical factors
AF-related stroke is associated with increased severity, disability
and mortality compared with non-AF-related stroke2-4
References:
1. Off beat: Atrial fibrillation and the cost of preventable strokes. Deloitte Access Economics, September 2011. 2. Gattellari M et al.
Cerebrovasc Dis 2011; 32: 370-82. 3. Lin HJ et al. Stroke 1996; 27: 1760-4. 4. Lamassa M et al. Stroke 2001; 32: 392-8.
Before prescribing, please review full Product Information available with this presentation.
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Appropriate Use of Anticoagulants is a Key Goal
of Stroke Prevention in AF
Risk Factor
C ongestive heart failure/LV dysfunction
H ypertension
A ge ≥ 75 years
D iabetes mellitus
S troke/TIA/TE
Score
1
1
2
1
2
V ascular disease (prior myocardial infarction, peripheral artery
disease, or aortic plaque)
1
A ge 6574 y
1
S ex category (ie female gender)
1
Reference: 1. Kirchhof P et al. Eur Heart J 2016; 37: 2893-962
NOAC: Non-vitamin K oral anticoagulant
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Anticoagulation is
recommended for CHA2DS2VASc score ≥2 (male) or ≥3
(female) (and should be
considered for a score of 1 or
2, respectively*)1
A NOAC is recommended in
preference to a vitamin K
antagonist for patients eligible
for anticoagulation1
Challenges in Managing Stroke Prevention in
AF with Warfarin
Warfarin has been shown to effectively reduce the risk of stroke, with a 64% relative risk
reduction vs placebo1
Despite this, 40–60% of eligible candidates for anticoagulation therapy in AF do not
receive appropriate treatment2,3
• Various reasons account for the underuse of warfarin, including:3,4
–
–
–
–
–
•
the requirement for regular INR monitoring
reluctance or refusal of some patients to take warfarin
physician concern of anticoagulant-induced haemorrhagic stroke
the challenge of managing unstable INR levels in certain patients
difficulties associated with drug interactions, contraindications, risk of falls and dietary restrictions
NOACs such as ELIQUIS offer an alternative treatment to warfarin for stroke prevention
in NVAF5
NOAC: non-vitamin K antagonist oral anticoagulant
References: 1. Hart RG et al. Ann Intern Med 2007; 146: 857-67.2. Off beat: Atrial fibrillation and the cost of preventable strokes.
Deloitte Access Economics, September 2011. 3. Sansom L. Review of anticoagulation therapies in atrial fibrillation, 2012. 4. Abcede
HG et al. Curr Treat Options Cardiovasc Med 2010; 12: 250-60. 5. Camm AJ et al. Europace 2012; 14: 1385-413.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS: a Direct and Highly Selective Inhibitor of Factor Xa1
• Factor Xa is the primary site of amplification in the coagulation cascade – one factor Xa
molecule leads to the formation of ~1000 thrombin molecules2
Adapted from Eriksson BI et al. 2011.3
Warfarin acts by inhibiting the synthesis of
vitamin K dependent coagulation factors VII,
IX, X and II, and prothrombin (not all shown).4
References: 1. ELIQUIS approved Product Information 2. Turpie AG. Arterioscler Thromb Vasc Biol 2007; 27: 1238-47. 3. Eriksson BI et
al. Annu Rev Med 2011; 62: 41-57. 4. Coumadin approved Product Information (19 January 2010).
ELIQUIS for Stroke Prevention in NVAF
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS for Stroke Prevention in NVAF
ELIQUIS is indicated for the prevention of stroke and systemic embolism in
patients with non-valvular atrial fibrillation and at least one additional risk
factor for stroke.1
ELIQUIS is also indicated for the prevention of venous thromboembolic
events (VTE) in adult patients who have undergone elective total hip or
total knee replacement surgery, for the treatment of DVT and PE, and for
the prevention of recurrent DVT and PE.1
Reference: 1. ELIQUIS Approved Product Information.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ARISTOTLE Trial – ELIQUIS vs Warfarin
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ELIQUIS: Superiority vs Warfarin in All of the
Following Important Outcomes1
Adapted from Granger
CB et al. 2011.1
"For every 1000 patients treated for 1.8 years, apixaban, as compared with warfarin,
prevented a stroke in 6 patients, major bleeding in 15 patients, and death in 8 patients."1
Reference: 1. Granger CB et al. N Engl J Med 2011; 365: 981-92.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ARISTOTLE: Additional Stroke Outcomes
Compared with warfarin, ELIQUIS also demonstrated the following:1
• 49% reduction in the risk of haemorrhagic stroke (p<0.001)
– 0.24% vs 0.47% per year
• 29% reduction in the risk of fatal or disabling stroke (HR 0.71; 95% CI, 0.54–0.94)
– 0.50% vs 0.71% per year (p value not reported)
• Similar rate of ischaemic or undetermined stroke (p=0.42, not significant)
– 0.97% vs 1.05% per year (HR 0.92; 95% CI, 0.74–1.13)
Reference: 1. Granger CB et al. N Engl J Med 2011; 365: 981-92.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS: Superior Safety Profile in Reducing Major
Bleeding vs Warfarin1
Primary safety endpoint
Adapted from Granger
CB et al. 2011.1
Major bleeding was defined, according to the ISTH criteria, as clinically overt bleeding accompanied by a decrease in the haemoglobin
level of at least 20 g/L or transfusion of at least 2 units of packed red cells, occurring at a critical site, or resulting in death.
Reference: 1. Granger CB et al. N Engl J Med 2011; 365: 981-92.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ARISTOTLE: Additional Bleeding Outcomes
Compared with warfarin, ELIQUIS also demonstrated a:1
• A 59% reduction in the risk of intracranial haemorrhage (p value not reported)
– 0.33% vs 0.82% per year
• No increase in major GI bleeding
– 0.83% vs 0.93% per year (HR 0.89; 95% CI, 0.70–1.14)
Fatal bleeding (including both fatal and extracranial bleeds and fatal
haemorrhagic stroke) occurred in 10 patients (0.06% per year) in the
ELIQUIS group and 37 patients (0.24% per year) in the warfarin group
(HR 0.27; 95% CI, 0.13–0.53).1
Reference: 1. ELIQUIS Approved Product Information.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS Real-world Data Complements Clinical Trial Data1,2†‡
†
Findings from the ARISTOTLE trial, a non-inferiority, phase III, randomised, double-blind trial in patients with NVAF and at least one additional risk factor for stroke.1
cohort analysis of NVAF patients receiving ELIQUIS, rivaroxaban, dabigatran or warfarin in a large USA insurance database (1 October 2010–30 June
2015).2
‡Retrospective
References: 1. Granger CB et al. N Engl J Med 2011; 365: 981-92. 2. Yao X et al. J Am Heart Assoc 2016; 5.
Before prescribing, please review full Product Information available with this presentation.
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AVERROES Trial – ELIQUIS vs Aspirin
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ELIQUIS: Superior Reduction in Risk of Stroke/Systemic Embolism
Without Increased Risk of Major Bleeding vs Aspirin1
►
The mortality rate
was 3.5% per year
with ELIQUIS and
4.4% per year with
aspirin (HR 0.79; 95%
CI 0.62–1.02; p=0.07,
not significant)1
Adapted from Connolly
SJ et al. 2011.1
This superiority study was terminated early due to a clear
benefit in favour of ELIQUIS for the primary endpoint1
Note: AVERROES population were warfarin-unsuitable; aspirin is not recommended for stroke prevention in AF
Reference: 1. Connolly SJ et al. N Engl J Med 2011; 364: 806-17.
Before prescribing, please review full Product Information available with this presentation.
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ELIQUIS: Superior Stroke/Systemic Embolism
Prevention vs Aspirin1
Primary efficacy endpoint
Adapted from Connolly
SJ et al. 2011.1
This superiority study was terminated early due to a clear
benefit in favour of ELIQUIS for the primary endpoint1
Reference: 1. Connolly SJ et al. N Engl J Med 2011; 364: 806-17.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS: No Significant Increase in Major Bleeding
vs Aspirin1
Primary safety endpoint
Adapted from Connolly
SJ et al. 2011.1
Reference: 1. Connolly SJ et al. N Engl J Med 2011; 364: 806-17.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
Antithrombotic Treatment Patterns for Patients with Newly
Diagnosed AF 1,2
“Antiplatelet monotherapy is not recommended for stroke prevention in AF patients,
regardless of stroke risk” – ESC Guidelines2
AP, antiplatelet; DTI, direct thrombin inhibitor; FXaI, factor Xa inhibitor; VKA, vitamin K antagonist
Reference: 1. Camm AJ et al. Heart 2016. 2. Kirchhoff P et al. Eur Heart J 2016; 37: 2893–962.
Before prescribing, please review full Product Information available with this presentation.
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Attributes of NOACs and Warfarin
Therapeutic class
Dosage for SPAF
Routine monitoring
Half-life
Renal elimination
ELIQUIS
apixaban1
Factor Xa inhibitor
5 mg BD
2.5 mg BDa
No
12 h
27% unchanged
XARELTO
rivaroxaban2
Factor Xa inhibitor
20 mg OD
15 mg Odb
No
5-9 hd
11-12 hc
33% unchanged
PRADAXA
dabigatran3
Direct thrombin inhibitor
150 mg BD
110 mg BDc
No
12-14 h
85% unchanged
Coumadin
warfarin4
Vitamin K antagonist
Variable
(to INR 2.0-3.0)
Yes
1 week
(terminal half-life)
40 h
(effective half-life)
None
a2.5mg
BD: patients with two or more of: age ≥80 years, weight ≤60kg, Serum creatinine ≥133 μmol/L.
OD: patients with moderate renal impairment (CrCl 30–49 mL/min).
c110mg BD: patients aged ≥75 years; also consider in patients with moderate renal impairment (CrCl 30–50 mL/min), high bleeding risk.
dIn young, healthy subjects.
eIn the elderly.
b15mg
References: 1. ELIQUIS approved Product Information 2. Xarelto approved Product Information (3 April 2012). 3. Pradaxa approved Product Information (15 April 2013). 4. Coumadin
approved Product Information.
ELIQUIS: Tolerability Profile
ELIQUIS – the #1 NOAC agent prescribed by cardiologists in Australia*4
NOAC: non-vitamin K antagonist oral anticoagulant. * For new NVAF patients
References: 1. Granger CB et al. N Engl J Med 2011; 365: 981-92. 2. Connolly SJ et al. N Engl J Med 2011; 364: 806-17.
3. ELIQUIS Approved Product Information. 4. NostraData Pty Ltd Hawthorn, Vic. Data on file
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS (apixaban): for the Treatment of Deep Vein
Thrombosis (DVT) and Pulmonary Embolism (PE)
and the Prevention of DVT/PE Recurrence
Before prescribing, please review full Product Information available with this presentation.
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ELIQUIS has a Demonstrated Efficacy and
Safety Profile Across Multiple Indications1,2
ELIQUIS is indicated for the following, in adult patients:
• Prevention of stroke and systemic embolism in patients with NVAF
and at least one additional risk factor for stroke
• Treatment of DVT
• Treatment of PE
• Prevention of recurrent DVT and PE
• Prevention of DVT/PE after elective total knee replacement surgery
• Prevention of DVT/PE after elective total hip replacement surgery
NVAF=nonvalvular atrial fibrillation.
Reference: 1. ELIQUIS Approved Product Information.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
Initial and long-term DVT/PE treatment
ELIQUIS, Compared with Enoxaparin/Warfarin, Demonstrated Comparable
Efficacy, with a Significant 69% Relative Risk Reduction in Major Bleeding1,2
RRR=relative risk reduction.
References: 1. ELIQUIS Approved Product Information. 2. Agnelli
G et al. N Engl J Med 2013; 369: 799-808.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
28
Initial and long-term DVT/PE treatment
ELIQUIS Demonstrated Relative Risk Reductions vs Enoxaparin/Warfarin
Across All Protocol-defined Bleeding Endpoints1,2
►
Fewer patients taking ELIQUIS (7/2676; 0.3%) experienced major GI bleeding†
vs those taking enoxaparin/warfarin (18/2689; 0.7%)2
* Prespecified secondary safety endpoint.
† Not a protocol-defined endpoint.
CRNM=clinically relevant non-major; GI=gastrointestinal; RRR=relative risk reduction.
References: 1. ELIQUIS Approved Product Information. 2. Agnelli
G et al. N Engl J Med 2013; 369: 799-808
Before prescribing, please review full Product Information available with this presentation.
Before
prescribing,
please review full Product Information available with this
For further information
please
go to www.eliquis.com.au
presentation. For further information please go to www.eliquis.com.au
29
12-Month Extension Trial
ELIQUIS 2.5 mg BD was Superior to Placebo in Reducing Risk of VTE
Recurrence, With a Major Bleeding Incidence Similar to Placebo*1,2
*The recommended dose for of ELIQUIS for prevention of recurrent DVT/PE is 2.5 mg BD after at least 6 months of treatment for DVT/PE1
ELIQUIS 5 mg BD data not shown; BD=twice daily.
References: 1. ELIQUIS Approved Product Information. 2. Agnelli
G et al. N Engl J Med 2013; 369: 799-808.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS: Dosing for your NVAF Patients
ELIQUIS is available in two doses – 5 mg and 2.5 mg, taken twice daily1
The recommended dose is 5 mg BD, with or without food.1
Criteria for dose reduction to 2.5 mg BD1
►
Prior to initiating ELIQUIS, liver function testing should be performed1
Reference: 1. ELIQUIS Approved Product Information.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS: Dosing for DVT/PE Patients
Only ELIQUIS offers a short, 7-day treatment initiation period for DVT/PE
treatment and a lower dose for extended therapy1,2
Initiation
10 mg BD
Long-term therapy
5 mg BD
Extended therapy
2.5 mg BD
AMPLIFY
7 days
►
►
AMPLIFY-EXT
≥6 months
ELIQUIS has a rapid onset of action, eliminating the need for injectable LMWH therapy
during initiation2
ELIQUIS has no known dietary restrictions and can be taken with or without food1
BD=twice daily; LMWH=low-molecular-weight heparin.
References: 1. ELIQUIS Approved Product Information. 2. Yamahira N et al. Int J Clin Pharmacol Ther 2014; 52: 564-73..
Before prescribing, please review full Product Information available with this presentation.
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32
Switching To and From ELIQUIS
VKA: Vitamin K antagonist. INR: International Normalised Ratio
References: 1.
ELIQUIS Approved Product Information. 2. Heidbuchel H et al. Europace 2015; 17: 1467-507.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
Management of Major Bleeding
Update in line with the new PI refer to PCC information
There is no clinical experience with the use of 4-factor PCC products to reverse bleeding in
individuals who have received ELIQUIS5
INR: International Normalised Ratio. aPTT: activated partial thromboplastin time. NOAC: non-vitamin K antagonist oral anticoagulant.
PCC: 3-factor prothrombin complex concentrate. PT: prothrombin time. rFVIIa: activated recombinant factor VII.
References: 1. Tran HA et al. Med J Aust 2013; 198: 198-9. 2. Coumadin approved Product Information. 3. Steiner T et al. Stroke
2006; 37: 256-62. 4. Camm AJ et al. Heart 2016. 5. ELIQUIS Approved Product Information.
Before prescribing, please review full Product Information available with this presentation.
For further information please go to www.eliquis.com.au
ELIQUIS® (Apixaban)
Indications
For use in adult patients for:
• DVT/PE prevention after elective total hip or total knee replacement surgery
• Stroke and systemic embolism prevention with non-valvular atrial fibrillation
(NVAF) with at least one additional factor for stroke
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
and prevention of recurrent DVT and PE.
PBS Information: Authority required (STREAMLINED)
Refer to PBS Schedule for full authority information.
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ELIQUIS® (Apixaban)
PBS Information: Authority required (STREAMLINED)
Refer to PBS Schedule for full authority information.
Before prescribing, please review full Product Information available from Bristol-Myers Squibb Australia Pty Ltd by calling 1800 067 567.
•
•
•
•
•
•
•
•
ELIQUIS® (apixaban) 2.5 mg and 5 mg tablets. Indications: For use in adult patients for DVT/PE prevention after elective total hip or total knee replacement surgery; stroke and
systemic embolism prevention with non-valvular atrial fibrillation (NVAF) with at least one additional factor for stroke; treatment of deep vein thrombosis (DVT) and pulmonary
embolism (PE) and prevention of recurrent DVT and PE.
Contraindications: Hypersensitivity to apixaban or tablet excipients; clinically significant active bleeding (intracranial, GI); impairment of haemostasis; hepatic disease associated with
coagulopathy and clinically relevant bleeding risk, severe hepatic impairment (Child-Pugh C); severe renal impairment CrCl < 25 mL/min; organ lesion or conditions at risk of clinically
significant major bleeding; strong inhibitors of both CYP3A4 and P-gp, concomitant anticoagulant treatments. See PI for details.
Precautions: Haemorrhage risk: existing conditions with increased bleeding risk; fall in haemoglobin or blood pressure – search for bleeding site; discontinue if severe haemorrhage or
complications; consider treatment. Increased risk of thrombotic events after premature discontinuation when transitioning to warfarin (consider coverage with another anticoagulant);
valvular heart disease; active cancer; acute pulmonary embolism in haemodynamically unstable patients or patients who require thrombolysis or pulmonary embolectomy; patients
with provoked DVT/PE; ischaemic stroke; renal or hepatic impairment; elevated liver enzymes or bilirubin; strong inducers of both CYP3A4 and P-gp; concomitant NSAIDs; other antiplatelets or antithrombotic agents not recommended; spinal/epidural anaesthesia or puncture; indwelling catheters; neuraxial blockade; hip fracture surgery; pregnancy; lactation;
children; elderly patients on concomitant acetylsalicylic acid; effects on clotting tests. See PI for details.
Interactions with other Medicines: inducers and inhibitors of both CYP3A4 and P-gp. See PI for details.
Adverse Effects: Most common: anaemia, haemorrhage (including eye, GI, rectal, gingival), haematoma, haematuria, epistaxis, contusion, nausea, menorrhagia. Others include:
thrombocytopenia, hypotension, haemorrhage: intra-abdominal, haemorrhoidal, mouth, vaginal, urogenital, operative, vessel/catheter/incision site, post-procedural bleeding,
haematochezia, liver enzymes increased or abnormal, bilirubin increased, wound secretion, haemoptysis, hypersensitivity. See PI for details.
Dosage and Administration: DVT/PE prevention: 2.5 mg twice daily. Start 12 to 24 hours after surgery. Take for 32-38 days in hip replacement and 10 -14 days for knee replacement.
NVAF: 5 mg twice daily; 2.5 mg twice daily in patients with at least two of the following characteristics: ≥ 80 yrs;
≤ 60 kg; serum creatinine ≥ 133 µmol/L. DVT/PE treatment: 10 mg twice daily for 7 days, followed by 5 mg twice daily. Prevention of recurrent DVT/PE: 2.5 mg twice daily after at least
6 months of treatment for DVT/PE. See PI for details.
Before prescribing, please review Product Information (Therapeutic Goods Administration, https://www.ebs.tga.gov.au/ ) 432AU1700005-02
Presentation End