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Jürgen is at significant risk of stroke and major bleeding CHA 2 DS 2 -VASc 1 = 4 Risk Factors 2 Points C Congestive heart failure/ LV dysfunction 1 HHypertension1 A2A2 Age ≥75 years2 DDiabetes mellitus1 S2S2 Stroke/TIA/thromboembolism2 VVascular disease a 1 AAge 65 to 74 years1 ScSex category (female)1 Maximum score9 HAS-BLED 2 = 3 a Vascular disease includes myocardial infarction, complex aortic plaque, and peripheral artery disease b Defined as uncontrolled hypertension (systolic blood pressure >160 mm Hg) LV, left ventricular; TIA, transient ischemic attack; INR, international normalized ratio Clinical CharacteristicsPoints HHypertension b 1 A Abnormal renal or hepatic function (1 point each) 1 or 2 SStroke1 B Bleeding history or predisposition 1 LLabile INRs1 EElderly (age >65 years)1 DDrugs or alcohol (1 point each)1 or 2 1. Lip et al. Chest 2010;137:263–72; 2. Pisters et al. Chest 2010;138:1093–100.
Citation preview
Case study - patient presenting with newly diagnosed NVAF with prior CAD
Full Prescribing Information is provided at the end of this presentation
EUAPI581k; Date of preparation: April 2014
NVAF, non-valvular atrial fibrillation; CAD, coronary artery disease
15.ELI.22.1443NL15PR04188-01
Patient profile – Newly diagnosed NVAF
* Patient is fictitious
MI, myocardial infarction; ECG, electrocardiogram; ASA, acetylsalicylic acid
Personal InformationSex MaleAge 77Weight 85 kg
Blood Pressure 161/92 mmHg
Personal • Retired
Patient: Jürgen*
Patient History
Medical History• MI two years ago• Hypertension• Dyslipidaemia
Medications• ASA• Atorvastatin• Metoprolol
Presentation
• Regular transient mild dyspnoea since a few weeks ago
• Diagnosed with NVAF on ECG during investigation
Jürgen is at significant risk of stroke and major bleeding
CHA2DS2-VASc1 = 4Risk Factors2 Points
C Congestive heart failure/LV dysfunction 1
H Hypertension 1A2 Age ≥75 years 2D Diabetes mellitus 1S2 Stroke/TIA/thromboembolism 2V Vascular diseasea 1A Age 65 to 74 years 1Sc Sex category (female) 1
Maximum score 9
HAS-BLED2 = 3
aVascular disease includes myocardial infarction, complex aortic plaque, and peripheral artery diseasebDefined as uncontrolled hypertension (systolic blood pressure >160 mm Hg)
LV, left ventricular; TIA, transient ischemic attack; INR, international normalized ratio
Clinical Characteristics Points
H Hypertensionb 1
A Abnormal renal or hepatic function (1 point each) 1 or 2
S Stroke 1
B Bleeding history or predisposition 1
L Labile INRs 1
E Elderly (age >65 years) 1
D Drugs or alcohol (1 point each) 1 or 2
1. Lip et al. Chest 2010;137:263–72;2. Pisters et al. Chest 2010;138:1093–100.
Question 1
Jurgen is newly diagnosed with NVAF and has a CHA2DS2-VASc score of 4 and a HAS-BLED score of 3. According to the 2012 ESC guidelines, a NOAC should be considered rather than adjusted-dose VKA (INR 2–3)1
Jurgen has hypertension and prior coronary artery disease
Would ELIQUIS® (apixaban) be a good option for Jürgen’s stroke prevention?
1. Yes
2. No
NOAC(s), novel oral anticoagulant(s); VKA, vitamin K antagonist
1. Camm et al. Eur Heart J 2012;33:2719–47.
Jürgen has a high risk of stroke as well as a high risk of bleeding and may benefit most from a therapy that protects against stroke and limits major bleeding
In ARISTOTLE, ELIQUIS® (apixaban) significantly reduced the rates of stroke/SE and major bleeding as compared to warfarin1
– In addition all-cause mortality was reduced significantly for ELIQUIS® (apixaban) vs warfarin1
Primary safety endpoint 0.00.51.01.52.02.53.03.54.0
2.13%
3.09%
ApixabanWarfarin (Target INR 2.0−3.0)
What about ELIQUIS® (apixban)
1. Granger et al. N Engl J Med 2011;365:981–92.
n=269
Stroke/ systemic embolism1 Major bleeding1
Primary efficacy endpoint 0.0
0.5
1.0
1.5
2.0
1.27%1.6%
n=212/9120
n=265/9081
n=327/9088
n=462/9052
21% RRR p=0.01 31% RRR p<0.001
SE, systemic embolism Adapted from Granger et al. N Engl J Med 2011;365:981–92
Even
t rat
e (%
/yea
r)
Even
t rat
e (%
/yea
r)
B. Major Bleeding1
Subgroup No. of patients Apixaban Warfarin Hazard Ratio (95% CI) P value for
interactionNo. of events (%/yr)
Age 0.63* < 65 yr 5,455 56 (1.17) 72 (1.51) 65 to < 75 yr 7,030 120 (1.99) 166 (2.82) ≥ 75 yr 5,655 151 (3.33) 224 (5.19)
1. Halvorsen et al. Eur Heart J 2014;Feb 20 [epub ahead of print];2. Connolly et al. N Engl J Med 2011;364:806–17.
Jürgen is 77 years old. What do we know about the ELIQUIS® (apixaban) data (ARISTOTLE) in elderly patients?1
0.25 0.50 1.00 2.00
Apixaban better Warfarin better
A. Primary Efficacy Outcome: Stroke and Systemic Embolism1
Subgroup No. of patients Apixaban Warfarin Hazard Ratio (95% CI) P value for
interactionNo. of events (%/yr)
Age 0.11* < 65 yr 5,471 51 (1.00) 44 (0.86) 65 to < 75 yr 7,052 82 (1.25) 112 (1.73) ≥ 75 yr 5,678 79 (1.56) 109 (2.19)
0.25 0.50 1.00 2.00
Apixaban better Warfarin better
*Interaction P-values based on continuous ageAdapted from Halvorsen et al. Eur Hear J 2014;Feb 20 [epub ahead of print]
In addition, in the AVERROES trial the effects of apixaban compared with ASA in the older patient subgroups (age ≤ 75 years) were consistent with the overall study population2
Prevalence in the REACH Registry1
Jürgen is put on ELIQUIS® (apixaban) 5 mg twice-dailyHow does his CAD influence his treatment?
1. Goto et al. Am Heart J 2008;156:855–63.
37,724 stable outpatients with CAD
87.5%
12.5%
Without AFWith AF
The REACH study was a large-scale international, prospective cohort study of 68,236 stable outpatients with established atherothrombosis or >= 3 atherothrombotic risk factors.
Adapted from Goto et al. Am Heart J 2008;156:855–63
Atrial Fibrillation and CAD frequently coincide
CAD patients with AF have a higher rate of major clinical events than CAD patients without AF1
Death / MI / stroke CV death Bleeding0
1
2
3
4
5
6
7
8
6.92%
3.42%
1.49%
4.3%
1.69%
0.81%
With AFWithout AF
Patie
nts (
%)
p<0.0001
p<0.0001
p<0.0001
CV, cardiovascular
1. Goto et al. Am Heart J 2008;156:855–63.
Adapted from Goto et al. Am Heart J 2008;156:855–63
37,724 patients with CAD: 12.5% prevalence of atrial fibrillation1
What data for ELIQUIS® (apixaban) in for stroke preventionin NVAF exist in patients with prior CAD?1
Of the study population in ARISTOTLE, 6,639 (36.5%) of patients had prior CAD
Patients with prior CAD were more often male and were more likely to have prior stroke, diabetes and hypertension as compared with patients without prior CAD
Patients with prior CAD were more likely to be on aspirin at baseline (42.2% vs 24.5%; p<0.001) when compared with patients without prior CAD
1. Bahit et al. Int J Cardiol 2013;170:215–20
Apixaban Warfarin HR (95% CI) No CAD CAD Interaction p value
Efficacy endpointsStroke or systemic embolism
1.15 (121)1.47 (91)
1.63 (171)1.55 (94)
0.704 (0.558, 0.889)0.950 (0.712,1,267) 0.11
Stroke 1.06 (112)1.40 (87)
1.52 (159)1.50 (91)
0.701 (0.550, 0.892)0.937 (0.699, 1.258) 0.14
Death (any cause) 3.11 (335)4.21 (267)
3.68 (395)4.40 (274)
0.847 (0.732, 0.979)0.958 (0.809, 1.133) 0.28
MI 0.29 (31)0.95 (59)
0.39 (41)1.00 (61)
0.755 (0.473, 1.203)0.947 (0.662, 1.354) 0.45
Revascularisation (PCI/CABG)
0.70 (74)1.69 (104)
0.67 (71)1.89 (114)
1.040 (0.751, 1.441)0.890 (0.682, 1.161) 0.47
Safety endpoints
ISTH major bleeding 1.99 (194)2.39 (123)
3.12 (297)3.05 (165)
0.640 (0.534, 0.766)0.784 (0.624, 0.985) 0.17
Intracranial bleeding 0.37 (37)0.27 (15)
0.85 (82)0.73 (40)
0.443 (0.301, 0.654)0.364 (0.201, 0.659) 0.59
Patients with or without prior CAD in ARISTOTLE1
1. Bahit et al. Int J Cardiol 2013;170:215–20
Adapted from Bahit et al. Int J Cardiol 2013;170:215–20
0.1 1 10
Favour apixaban Favour warfarin
MI, myocardial infarction; ISTH, International Society on Thrombosis and Haemostasis
Conclusion of the subanalysis of patients with prior CAD in ARISTOTLE
In patients with NVAF, ELIQUIS® (apixaban) prevents stroke or systemic embolism and causes less major bleeding and death compared with warfarin
These treatment effects were consistent in patients with and without a history of CAD
As the combination of NVAF and CAD commonly occurs and as there are higher rates of CV events and death in these patients, ELIQUIS® (apixaban) may be a better option than warfarin in this high-risk group
1. Bahit et al. Int J Cardiol 2013;170:215–20
Question 2
Jürgen is now on ELIQUIS® (apixaban) for stroke prevention in NVAF and is also still taking aspirin given his prior CAD. His CAD has been stable ever since he has had the MI 2 years ago
Can Jürgen discontinue taking ASA?
1. Yes, ASA can be discontinued
2. No, he still needs ASA
ELIQUIS® (apixaban) and antiplatelet therapy in NVAF patients
In ARISTOTLE, concomitant use of ASA increased the major bleeding risk:1
1. Apixaban SmPC. Available at http://www.ema.europa.eu
OAC alone OAC + ASA0
0.51
1.52
2.53
3.54
4.55
1.8%
3.4%
2.7%
4.6%
Major bleeding in ARISTOTLE1
Apixaban VKA
(%) o
f eve
nts
There was limited (2.1%) use of concomitant dual antiplatelet therapy1
Created from Apixaban SmPC
Concomitant use of ELIQUIS® (apixaban) with antiplatelet agents increases the risk of bleeding1
Care is to be taken if patients are treated concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid
In patients with NVAF 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 apixaban
1. Apixaban SmPC. Available at http://www.ema.europa.eu
In ARISTOTLE, concomitant ASA use was left to the discretion of the treating physician1
On Day 1, 4434 (24%) of patients were taking ASA1
Event rates for apixaban vs warfarin in patients on ASA vs no ASA:
Apixaban benefits vs warfarin were consistent for patients taking or not taking ASA1
What do we know about the use of concomitant ASA in patients using apixaban?
1. Alexander et al. Eur Heart J 2014;35:224–32
Apixabanevent rate (%/year)
Warfarinevent rate(%/year)
HR (95% CI) ASA No ASA Interaction p value
Stroke or systemic embolism
41 (1.12)127 (1.11)
67 (1.91)149 (1.32)
0.58 (0.39–0.85)0.84 (0.66–1.07) 0.10
Ischaemic stroke 29 (0.79)95 (0.83)
40 (1.14)94 (0.83)
0.69 (0.43–1.11)1.00 (0.75–1.33) 0.19
Myocardial infarction 33 (0.90)46 (0.40)
26 (0.74)58 (0.51)
1.20 (0.71–2.00)0.78 (0.53–1.14) 0.19
Death 71 (1.93)188 (1.64)
64 (1.82)223 (1.97)
1.05 (0.75–1.47)0.83 (0.68–1.00) 0.23
Major bleeding 114 (3.10)211 (1.82)
138 (3.92)317 (2.78)
0.77 (0.60–0.99)0.65 (0.55–0.78) 0.29
Haemorrhagenic stroke 10 (0.27)25 (0.22)
24 (0.68)47 (0.42)
0.40 (0.19–0.83)0.53 (0.33–0.86) 0.52
Major or CRNM bleeding 199 (5.54)410 (3.59)
246 (7.18)620 (5.58)
0.76 (0.63–0.92)0.65 (0.57–0.73) 0.15
Any bleeding 682 (22.64)1657 (16.61)
859 (32.84)2180 (23.72)
0.70 (0.62–0.77)0.71 (0.67–0.76) 0.70
0.1 1 10Favour apixaban Favour warfarin
EHRA guidance on concomitant ASA1
Stable CAD patients developing AF should receive anticoagulation, depending on their CHA2DS2-VASc score
Anticoagulation without additional antiplatelet agents is considered sufficient for most AF patients with stable CAD (acute coronary syndrome ≥1 year ago; elective bare-metal stent ≥1 month; drug-eluting stent ≥6 months)
The advantages of NOACs over VKA are likely to be preserved in stable CAD patients. NOACs may be an appropriate and effective alternative to VKAs
1. Heidbüchel et al. Europace 2013;15:625–51.
Question 2
Jürgen is now on ELIQUIS® (apixaban) for stroke prevention in NVAF and is also still taking aspirin given his prior CAD. His CAD has been stable ever since he has had the MI 2 years ago
Can Jürgen discontinue taking ASA?
1. Yes, ASA can be discontinued
2. No, he still needs ASA
Patient case: Key learnings
1. Bahit et al. Int J Cardiol 2013;170:215–220; 2. Alexander et al. Eur Heart J 2014;35:224–232; 3. Heidbüchel et al. Europace 2013;15:625–651.
This high-risk patient may benefit most from a therapy that protects against stroke while limiting major bleeding
– In ARISTOTLE, ELIQUIS® (apixaban) significantly reduced the risk of stroke/SE and major bleeding as compared to warfarin
The results of the ARISTOTLE trial were consistent in predefined subgroups according to:
– Prior coronary artery disease1
– Use of ASA2
According to the EHRA practical guide on the use of NOACs in NVAF, anticoagulation without additional antiplatelet agents is considered
sufficient for most patients with stable CAD3
ELIQUIS® (apixaban) 2.5 mg & 5 mg FILM-COATED TABLETS PRESCRIBING INFORMATION
SMPC link, click here