How To Ensure Protection

Beyond Stroke Prevention in

High-Risk AF Patients
Dr. dr. Eka Fithra Elfi, Sp.JP (K)​
Department of Cardiology and Vascular Medicine​
Division of Vascular Medicine​
Faculty of Medicine Andalas University - Dr. M. Djamil General Hospital​
Padang-Indonesia​
 Conflict of Interest
• I was appointed by Symposium Committee as Speaker, thus I receive Speaker
Compensation from Committee.
• I have no special attachment to any specific medical company
• My interest is only and only to provide updated information regarding cardiovascular
management to other medical professional
 Case illustration
• A 69 yo female with
hypertension and diabetes was
admitted with hemiplegia and
decrease of consciousness.
• Her ECG shown in the right
• She was consulted to neurology
• How we prevent this event in
the future and for other similar
patients who have not had a
stroke.
 Atrial Fibrillation and stroke
• Atrial Fibrillation (AF) is the most
common cardiac arrhythmias
• Clinical manifestation includes
palpitation, dyspnea, chest pain,
syncope, thromboembolism, and
death
• Stroke is one of major problem of AF
complication and the second acute
cardiovascular condition after
myocardial infarction
 Epidemiology of AF: Prevalence
Figure 2 (1) Epidemiology of AF: prevalence

©ESC
Hindricks
2020 ESC Guidelines for the diagnosis and management G et al,
of atrial Eur Heart J 2020
fibrillation
www.escardio.org/guidelines
Epidemiology of AF: Lifetime Risk and Projected Rise in the
Incidence and Prevalence

Figure 2 (2)
Epidemiology of AF:
lifetime risk and
projected rise in the
incidence and
prevalence

aSmoking, alcohol consumption, body mass index, BP,

diabetes mellitus (type 1 or 2), and history of myocardi
infarction or heart failure. bRisk profile: optimal − all ris
factors are negative or within the normal range; border
no elevated risk factors but >1 borderline risk factor;
elevated − >1 elevated risk factor.

www.escardio.org/guidelines Hindricks
2020 ESC Guidelines for the diagnosis andG et al, Eur Heart
management J 2020
of atrial fibrillati
 AF Increases Risk for Stroke, Heart Failure and Mortality

Independent risk factor for stroke

• Approximately fivefold increased risk1
• 1 in 6 strokes occur in patients with AF2
• AF-related strokes are typically more severe than strokes due to other aetiologies3,4
• Stroke risk is unaltered even in patients with asymptomatic or intermittent AF5

Independent risk factor for mortality

• Approximately twofold increased risk6

Independent risk factor for heart failure

• Heart failure further aggravates AF, worsening overall prognosis7

1. Wolf PA et al. Stroke 1991;22(8):983-988; 2. Fuster V et al. Circulation 2006;114(7):e257-e354;

3. Lin HJ et al. Stroke 1996;27(10):1760-1764; 4. Jørgensen HS et al. Stroke 1996;27(10):1765-1769;
5. Page RL et al. Circulation 2003;107(8):1141-1145; 6. Benjamin EJ et al. Circulation 1998;98(10):946-952; 7. Wang T et al. Circulation 2003;107(23):2920-2925
 Classification of AF

AF Pattern Definition
First diagnosed AF not diagnosed before, irrespective of its duration or the presence/severity of AF-related symptoms
Paroxysmal AF that terminates spontaneously or with intervention within 7 days of onset
Persistent AF that is continuously sustained beyond 7 days, including episodes terminated by cardioversion
(drugs or electrical cardioversion) after ≥7 days
Long-Standing Continuous AF of >12 months’ duration when decided to adopt a rhythm control strategy
Persistent
Permanent AF that is accepted by the patient and physician, and no further attempts to restore/maintain sinus
rhythm will be undertaken. Permanent AF represents a therapeutic attitude of the patient and
physician rather than an inherent pathophysiological attribute of AF, and the term should not be used
in the context of a rhythm control strategy with antiarrhythmic drug therapy or AF ablation. Should a
rhythm control strategy be adopted, the arrhythmia would be reclassified as ‘long-standing persistent
AF’

Hindricks G et al, Eur Heart J 2020

 Risk Factors of AF
Coronary Artery Vascular Disease
Valve Heart Failure Disease (subclinical Physical
Disease atherosclerosis) Inactivity/intense activity

(Borderline) Ageing
Hypertension Lipid profile

(Pre-) Diabetes Genetics

AF Ethnicity
(Non-Caucasian) Alcohol
Consumption

Chronic Kidney
Disease Male Sex
Smoking

Inflammatory Obesity
Disease Acute Illness,
Purple: Cannot be modified COPD Obstructive Sleep
Blue: Can be modified Surgery
Pink: Correlation with heart Apnea
Yellow: Can occur anytime

Hindricks G et al, Eur Heart J 2020

 2021 APHRS Guideline: Key Recommendations for AF Screening

*ECG confirmation is required for a pulse-based screening method

**Hindricks et al. Eur Heart J. 2021;42(5):373-498

~Aged >50 years; left atrium dimension >4.0 cm on echocardiogram; mitral valve area <0.1 cm2 ; mitral valve calcification; mitral valve gradient >10 mmHg; New York Heart Association Class II or more
ECG, electrocardiogram; PPG, photoplethysmography; OAC, oral anticoagulant; RHD, rheumatic heart diseases

Chan et al. Journal of Arrhythmia. 2022;38:31–49.

AF Screening Tools

Sensitivity and specificity of various AF screening tools considering the 12-lead ECG as the gold
standard Sensitivity Specificity
Pulse taking 87 - 97% 70 - 81%
Automated BP
93 - 100% 86 – 92%
monitors
Single lead ECG 94 - 98% 76 - 95%
Smartphone apps 91.5 - 98.5% 91.4 - 100%
Watches 97 - 99% 83 - 94% Hindricks G et al, Eur Heart J 2020
 2021 APHRS Guideline: Recommendations on
Primary Stroke Prevention by AF Screening
Consensus Statement / Recommendation Level

Opportunistic screening for AF is recommended for people aged ≥ 65 years by pulse palpation followed by an
ECG confirmation. Alternatively, a 30 second rhythm strip could be used as the primary method of screening.
1

Systematic screening may be considered to detect AF in people aged ≥ 75 years or those with at high stroke
risk. 2

Consideration of healthcare and social economic issues, patients’ concerns and proper management of
screen-detected AF is important.
1

An ECG (12-lead or single-lead ≥ 30s) showing AF analyzed by a physician with expertise in ECG rhythm
interpretation is required to establish a definitive diagnosis of AF.
1

Chan et al. Journal of Arrhythmia. 2022;38:31–49.

 CHA2DS2-VASc-Score and HAS-BLED Risk Score

Risk factor Points Clinical characteristic1 Points

Hypertension 1
(systolic BP >160 mm Hg)
Congestive heart failure* 1
Abnormal renal or liver function
Hypertension 1 (Dialysis, transplant, serum creatinine >200 mmol/L, 1+1
cirrhosis, bilirubin > x 2 upper limit of normal,
AST/ALT/ALP >3 x upper limit of normal)
Age ≥75 years 2
Stroke
Age 65–74 years 1 1
(Previous ischemic or hemorrhagic stroke)

Diabetes mellitus 1 Bleeding

(Previous major hemorrhage or anemia or severe 1
thrombocytopenia)
Prior Stroke/ 2 Labile INRs
TIA or systemic embolism 1
(TTR <60% in patient receiving VKA)

Elderly 1
Female gender (Sex) (age >65 years)
1
Drugs or alcohol
(Concomitant use of antiplatelet or NSAID; and/or 1+1
Vascular disease 1 excessive alcohol per week)
Cumulative score Range 0−9
*Or moderate-to-severe left ventricular systolic dysfunction (left ventricular ejection fraction ≤40%).

Olesen JB et al. BMJ 2011;342:d124; Camm AJ et al. Eur Heart J. 2010;31(19):2369-2429

Pisters R et al. Chest 2010;138(5):1093-1100
 AF Management Strategies
• Three objectives: rate control, rhythm control, and prevention of thromboembolism1
• Rate control
• Control of the abnormally fast heart rate
• Rhythm control
• Correction of sinus rhythm disturbance
• Rate or rhythm control?
• Guidelines take factors like AF type, age, comorbidities, symptoms, and patient preferences into
account1,2
• AFFIRM, RACE: no difference in the two strategies regarding mortality or morbidity outcomes3,4

Regardless of whether rate or rhythm control is used to manage AF,

prevention of thromboembolism remains key1,5

1. Fuster et al. Circulation 2006; 2. National Collaborating Centre for Chronic Conditions. 2006;
3. Wyse et al. N Engl J Med 2002; 4. Van Gelder et al. N Engl J Med 2002; 5. Lip & Tse. Lancet 2007
 DOACs are the Standard of Care for Stroke Prevention in Eligible Patients
with AF*
Recommendations Class Level

For stroke prevention in AF patients who are eligible for OAC, NOACs are recommended in
preference to VKAs (excluding patients with mechanical heart valves or moderate-to-severe I A
mitral stenosis)

In patients on VKAs with low time in INR therapeutic range (e.g. TTR<70%), recommended
options are: I B
• Switching to a NOAC but ensuring good adherence and persistence with therapy; or

• Efforts to improve TTR (e.g. education/counselling and more frequent INR checks) IIa B

Antiplatelet therapy alone (monotherapy or aspirin in combination with clopidogrel) is not III
recommended for stroke prevention in AF (harm) A

*Those without mechanical heart valves or moderate or severe mitral stenosis

Hindricks G et al, Eur Heart J 2020

 Determining Eligible AF Patients for OAC
Mechanical heart valves or moderate or severe mitral stenosis VKA†
Yes
No
Step 1: Low stroke risk? Yes
No antithrombotic
CHA2DS2-VASc: 0 (males) or 1 (females) treatment
No
Step 2
Consider stroke prevention if CHA2DS2-VASc:
≥1 (males) or ≥2 (females)
Address modifiable bleeding risk factors
Calculate HAS-BLED score‡

CHA2DS2-VASc CHA2DS2-VASc
1 (males) or 2 (females) ≥2 (males) or ≥3 (females)
Oral anticoagulation should be considered (IIa) Oral anticoagulation is recommended (IA)

Step 3: Begin NOAC (or VKA†). NOACs are recommended as first line
With high time in therapeutic range; ‡If HAS-BLED is ≥3, address modifiable bleeding risk factors and flag patient for review and follow up. High bleeding risk score should not be a reason to
†

withhold OAC.

Hindricks G et al. Eur Heart J 2020; doi: 10.1093/eurheartj/ehaa612.

 There Are Many Limitations of VKA
Therapy
• Significant inter- and intra-patient variability in Risk of Risk of
ischaemic events bleeding events
dose–response,1 due to:
• Co-morbid conditions
• Genetic polymorphisms
• Numerous interactions with food and concomitant
drugs
• Unpredictable pharmacology
• Narrow therapeutic window1
• Regular coagulation monitoring and dose
adjustments required
Target
• Failure to stay within the therapeutic range increases INR 2–3
the risk of stroke or adverse bleeding events2
• Underuse2–4
• Fear of haemorrhage; intracranial haemorrhage is
the most devastating bleeding event5
• Particularly in elderly patients because of high
perceived risk of bleeding versus possible benefits5
INR < 2 INR > 3
1. Ansell J et al. Chest 2008;133(6 Suppl):160S-198S; 2. Nieuwlaat R et al. Am Heart J. 2007;153(6):1006-1012;
3. Ogilvie IM et al. Am J Med. 2010;123(7):638-645; 4. Nieuwlaat R et al. Eur Heart J. 2005;26(22):2422-2434; 5. Waldo A et al. J
Am Coll Cardiol 2005;46(9):1729-1736 ; 6. Ferreiro JL et al. Thromb Haemost. 2010;103(6):1128-1135
 Protection Is Both Efficacy and Safety: DOACs Showed a
Favourable Benefit–Risk Profile Versus Warfarin
Meta-analysis of phase III trials for stroke/SE prevention in
patients with AF demonstrated:

14% reduction 25% increase

19% reduction in major in GI bleeding
in stroke/SE bleeding
52% reduction
in ICH

The relative efficacy and safety of DOACs was consistent

across a wide spectrum of patients with AF

Ruff CT et al. Lancet 2014;383:955–962.

 Protection Is Both Efficacy and Safety: DOACs Deliver Greater Overall
Benefit than VKAs
DOACs are associated with a significant reduction in:
 Haemorrhagic stroke (with a strong trend towards lower rates of ischaemic stroke)
 All-cause mortality (with a trend towards lower rates of myocardial infarction)
 Intracranial haemorrhage

Whereas the risk of gastrointestinal bleeding is increased

Pooled NOAC Pooled warfarin RR

(events) (events) (95% CI) p-value

Efficacy
Ischaemic stroke 665/29,292 724/29,221 0.92 (0.83–1.02) 0.10
Haemorrhagic stroke 130/29,292 263/29,221 0.49 (0.38–0.64) <0.0001
Myocardial infarction 413/29,292 432/29,221 0.97 (0.78–1.20) 0.77
All-cause mortality 2022/29,292 2245/29,221 0.90 (0.85–0.95) 0.0003
Safety
Intracranial haemorrhage 204/29,287 425/29,211 0.48 (0.39–0.59) <0.0001

Gastrointestinal bleeding 751/29,287 591/29,211 1.25 (1.01–1.55) 0.043

0.2 0.5 1 2
Favours
Favours DOAC
warfarin

Ruff CT et al. Lancet 2014;383:955–962.

 We Are Anticoagulating Patients with AF to Prevent Strokes, But Can We
Do More?

Every 2 seconds, someone has a stroke 1

Every 5 seconds, someone dies from a stroke 1

1 in 4 of us will suffer a stroke 2

…but up to 80% of strokes can be avoided1

1. The Economist Intelligence Unit. 2017. Preventing Stroke: Uneven Progress. 2. The GBD 2016 Lifetime Risk of Stroke Collaborators. N Engl J Med 2018;379:2429–2437.
 Protection Doesn’t Start with a Prescription;
Modification of Known Risk Factors Helps to Prevent Stroke

Hypertension control
Smoking cessation

Stroke
Anticoagulation
treatment of AF Diabetes prevention

Eliminate excessive Cholesterol management

alcohol consumption

AHA, ASA. Your risk for stroke and how to be prepared. 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/ (accessed Feb 2020).
 Pharmacological Characteristics of DOAC1–10
Xabans DTI
Rivaroxaban Apixaban Edoxaban Dabigatran
Target Factor Xa Factor Xa Factor Xa Thrombin
Prodrug No No No Yes
Oral bioavailability 80–100%* 50% 62% 6.5%
Renal clearance of
absorbed active drug 33% 27% ~55-60% >80%

Tmax (h) 2–4 1–3 1–2 2–6#

Half-life (h) 5–13 8–13 10–14 12–14
Fixed Dosing
OD BID OD BID
(SPAF indication)
Renal impairment dosing
15mg 2.5mg 30mg 110mg
(30-49 ml/min)
*15–20 mg to be taken with food; #Postoperative period;

1. Eriksson BI et al. Annu Rev Med. 2011;62:41-57; 2. Frost et al. J Thromb Haemost. 2007;5(Suppl 2):P-M-664;
3. Kubitza D et al. Clin Pharmacol Ther. 2005;78(4):412-421; 4. Ogata K et al. J Clin Pharmacol. 2010;50(7):743-753;
5. Stangier J et al. J Clin Pharmacol 2005;45(5):555-563; 6. Dabigatran SmPC; 7. Apixaban SmPC; 8. Rivaroxaban SmPC; 9. Edoxaban SmPC; 10. Heidbuchel et al. Europace 2013;15(5):625-651
 ROCKET AF: Effective Stroke Prevention in Patients with Significant Reduction of
Critical Organ, ICH and Fatal Bleeding vs. Warfarin
Primary efficacy endpoint: Stroke/SE
HR 0.69
5 1.5 Warfarin Rivaroxaban
(95% CI 0.53–0.91)
Rivaroxaban
Cumulative event rate

p=0.007 HR 0.67
4 Warfarin
(95% CI 0.47–0.93)

Event rate (%/year)

RRR
1.2 p=0.02
3 1 31%
(%)

RRR RRR HR 0.50

2 21% 33% 95% CI 0.31 – 0.79

0.8 p=0.003

1 HR 0.79 (95% CI 0.66–0.96) 0.5 0.7 RRR

p<0.001 (non-inferiority) 0.5 0.5 50%

0
0 120 240 360 480 600 720 840 0.2
0
Days since Critical organ ICH Fatal bleeding
randomization bleeding
Rivaroxaban showed 21% reduction risk of stroke and significant reduction in terms
of Critical Organ, ICH and Fatal Bleeding compared to warfarin
PPP=Per-protocol population on-treatment=all ITT patients without major predefined protocol violations.

Patel MR et al. N Engl J Med. 2011;365(10):883891

 Patients with AF at Moderate or High Risk of Stroke Often Have Co‑morbid
Diabetes and/or CKD and Are Elderly

Age Hypertension Stroke

Mean 70.2 years ~4 in 5 patients 1 in 10 patients

CKD
BMI CAD
(GFR <60 ml/min)
Mean 27.5 kg/m2 1 in 5 patients
1 in 10 patients

Smoking Peripheral vascular

Diabetes
(current/previous) disease
1 in 5 patients
1 in 3 patients ~1 in 10 patients

GARFIELD-AF, cohort 1 (n=10,641)

Kakkar AK et al. PLoS One 2013;8:e63479.

Old Age Was Associated with Higher Risk of ICH, Major Bleeding, and
Ischemic Stroke

Chao, et al.Chest. 2020 May;157(5):1266-1277

 NOACs compared to Warfarin in the very elderly (≥90 years) AF Patients

+Adjusted for congestive heart failure, malignancy, and major bleeding. #Adjusted for congestive heart
failure, malignancy, and major bleeding, with mortality being the competing risk.

Chao TF, Gregory Y.H. Lip, Chen SA. Circulation 2018;138:37-47

The Risk Difference of ICH Between Warfarin and NOACs is Even More
Evident in the Elderly

Chao, et al.Chest. 2020 May;157(5):1266-1277

 Rivaroxaban Effective in Elderly AF Patients (≥75 Years
Background Primary endpoint: Stroke/SE
6 Warf. ≥75 years
 Prevalence of AF increases with age Riva. ≥75 years
2.85%/yr

probability of stroke/SE (%)

 Age alone is an important risk factor for stroke 1,2 5 2.29%/yr

Estimated cumulative
 After the age of 55 years, the stroke risk doubles for each 10 4 RRR
years of life3
3 20%
 Anticoagulation with warfarin reduces the risk of stroke
by ~60% in patients with AF4 2 HR (95% CI) riva. vs. warf.:
 Warfarin use in elderly patients is associated with a 1 ≥75 years: 0.80 (0.63–1.02);
higher risk of bleeding than in younger patients 5
0
0 6 12 18 24
Months from randomization
Results
Age ≥75 years (%/year) HR
 6,229 patients (44%) were aged ≥75 years at enrolment (95% CI)
Riva. Warf.
 Means CHADS2 Score in elderly group 3.7
 Elderly patients had similar rates of efficacy and safety Major bleeding 4.86 4.40 1.11 (0.92 – 1.34)
outcomes, whether they were receiving Xarelto® or ICH 0.66 0.83 0.80 (0.50 – 1.28)
warfarin
Critical Organ 1.07 1.42 0.75 (0.52 – 1.08)
Fatal Bleeding 0.28 0.61 0.45 (0.23 – 0.87)
Halperin JL et al. Circulation 2014;130(2):138-146
 The 2020 ESC Guidelines for the Management of AF Highlight the Importance of
Managing Co-morbidities Such as T2D
The Atrial Fibrillation Better Care (ABC) is a holistic approach with the patient at the centre

A C
Co-morbidities/
Anticoagulation/
CV risk factor
Avoid stroke
management

B
Better symptom The “C” component
control highlights the
importance of
management of diabetes
and/or CKD in patients
with AF
Treat AF: The ABC pathway
Hindricks G et al. Eur Heart J 2021;42:373–498.
 Why do we need to care for renal impairment in AF patients receiving
anticoagulant therapy?
 Patients with Atrial Fibrillation and Renal Impairment Are at High Risk of Bleeding and Stroke

~40% ~60% ~60%

increase increase increase

Stroke Mortality Bleeding

events

64% of patients with NVAF have renal Renal impairment increases the risk of
impairment1,2 stroke, bleeding events and mortality in
patients with NVAF2,3

Furthermore, in some warfarin-treated patients with AF, accelerated chronic kidney disease progression and acute
kidney injury can occur in association with excessive anticoagulation 4,5

1. Olesen JB et al, N Engl J Med 2012;36:625–635; 2. Fanikos J et al, Am J Med 2017;130:10151023; 3. Boriani G et al, Sci Rep 2016;6:30271;
4. Brodsjy SV et al, Nephron Clin Prac 2011;80:181–189; 5. Brodsky SV et al, Nephron Clin Prac 2011;115:c142–146
 Overlapping Comorbidities Increase the Complexity of Stroke Prevention
Particularly in AF Patients
• Up to 40% of AF patients have
DM1–3 • 65% of patients with AF have
• DM is an independent risk renal impairment6
factor for stroke in patients with • CKD is associated with an
AF (RR: 1.7)4
AF increased risk of developing AF
• Risk of death following a stroke and vice versa7, as well as
is greater for patients with vs bleeding8,9
without DM5

Diabetes Renal
mellitus Impairment

• Microvascular complications in DM can damage the kidneys 10

• Diabetic kidney disease occurs in around one-third of patients with type 2 DM11

1. Patel MR et al. N Engl J Med 2011;365:883–891; 2. Giugliano RP et al. N Engl J Med 2013;369:2093–2104; 3. Granger CB et al. N Engl J Med 2011;365:981–992; 4. The Stroke Risk in Atrial Fibrillation Working Group. Neurology 2007;69:546–554; 5.
Bansilal S et al. Am Heart J 2015;170:675–682.e8; 6. Boriani G et al. Sci Rep 2016;6:30271; 7. Boriani G et al. Europace 2015;17:1169–1196; 8. Kirchhof P et al. Eur Heart J 2016;37;2893–2962; 9. Olesen JB et al. N Engl J Med 2012;367:625–635;
10. Beckman JA et al. JAMA 2002;287:2570–2581; 11. Pecoits-Filho P et al. Diabetol Metab Syndr 2016;8:50.
 In AF Patients, VKA Use May Exacerbate Renal Decline,
Which May be Due to Increased Vascular Calcification
55 No VKA exposure (n=7023) 50 Warfarin
VKA exposure (n=7409) 45 Control† p=0.001

Arterial calcification (%)*

40
eGFR (mL/min/1.73 m2)

35
50
30
25
20
45 15
10
p=0.009
at 5 yrs exposure 5
40 0
0 1 2 3 4 5 <1 year 1–5 years >5 years
(n=123) (n=124) (n=141)
Follow-up (years)
Duration of warfarin therapy

 In patients with AF and CKD, renal function declines faster in  Arterial calcification is increased in warfarin-treated patients vs
those with VKA exposure vs no VKA exposure1 control patients2
*Calcification analysis in X-rays of lower extremity arteries at knee level and below. †Control: subject without a history of warfarin use.

1. Posch F et al. Presented at ÖGIM 2017, poster 07; 2. Han KH, O’Neill WC. J Am Heart Assoc 2016;5:e002665.
 Safety also means safeguarding ageing kidneys against the effects of treatment
AF patients1 Events (n) HR (95% CI)
Rivaroxaban (N=2485)

≥30% decline in eGFR 208 0.73 (0.62–0.87)

Doubling of creatinine 21 0.46 (0.28–0.75)

Acute kidney injury* 145 0.69 (0.57–0.84)

Kidney failure† 14 0.63 (0.35–1.15)

0.1 1 10
Favours Favours
Cited in 2019 rivaroxaban warfarin
guideline update2

“Over time, DOACs (particularly dabigatran and rivaroxaban) may be associated with lower risks
of adverse renal outcomes than warfarin in patients with AF”
*Defined as a hospitalisation or emergency department visit with a diagnosis code of AKI at the primary or secondary position; †Defined as eGFR <15 mL/min/1.73 m2, having kidney transplant, or
undergoing long-term dialysis.
1. Yao X et al. J Am Coll Cardiol 2017;70:2621–2632; 2. January CT et al. Circulation 2019; doi.org/10.1016/j.jacc.2019.01.011.
 How Can Patients with NVAF and T2D Be Protected from Vascular Death and Clinically
Relevant Bleeding?
Vascular death and clinically relevant bleeding were significantly lower with Rivaroxaban versus warfarin in
patients with NVAF and T2D
Rivaroxaban Warfarin
HR (95% CI) HR (95% CI)‡
(n=32,078)* (n=83,971)#

Stroke/SE or vascular death 1.79 1.79 0.91 (0.88–0.95)

Vascular death 2.81 3.18 0.90 (0.86–0.95)

Stroke/SE 1.31 1.34 0.97 (0.90–1.04)

Hospitalization for
major/CRNM bleeding 2.17 2.31 0.94 (0.89–0.99)

Critical organ bleeding 0.35 0.54 0.63 (0.55–0.72)

Intracranial
haemorrhage 0.29 0.40 0.72 (0.62–0.84)
0.5 1 2

*31% of patients initiated reduced 15 mg od dose. Favours Favours

#
Time in therapeutic range 47±28%. ‡Significant values are highlighted in magenta Rivaroxaban warfarin

Coleman CI et al. Cardiovasc Diabetol 2021;20:52.

 The Importance of Treatment Choice in Preserving Kidney Health in Patients with
AF and Diabetes is Increasingly Evident
RELOADED: Patients with AF and diabetes

HR (95% CI) vs VKA*

End-stage renal disease/dialysis Acute kidney injury

Rivaroxaban (n=6997) 0.32 (0.19–0.53) 0.72 (0.53–0.97)

Apixaban (n=5438) 0.60 (0.40–0.89) 1.07 (0.82–1.41)

Edoxaban (n=865) N<5 0.56 (0.23–1.37)

For the risk of acute kidney injury, only Xarelto® showed a risk reduction (28%)

On-treatment analysis.
*Phenprocoumon (n=8545).
Bonnemeier H et al. ESOC. Milan, Italy, 22–24 May 2019, AS25-069.
How do we give DOAC to prevent stroke?
How do we manage Bleeding?

European Cardiology Review 2021;16:e23.

 Summary
 The prevalence of AF is increasing in Asia pacific which followed by consequent rise in AF-
related hospitalization and burden to the healthcare system. Chronic rheumatic heart disease, an
important underlying cause for AF, remains a common condition in some Asia Pacific countries
 AF Patients and renal impairment are at higher risk of bleeding and stroke and lower eGFR is associated
with cardiovascular events and death
 Increasing CHA2DS2-VASc Score is associated with increasing renal decline, VKA may exacerbate renal
decline, which may be due to increased vascular calcification
 CHA2DS2-VASc and HAS-BLED are useful scores to predict risk of stroke, identify patients in need of
anticoagulant and provide bleeding risk of patients with AF.
 DOACs has demonstrated non-inferiority to warfarin in the prevention of stroke or systemic embolism,
with similar and sometimes less overall bleeding
 Several direct oral anticoagulants have been recommended in multiple guidelines. The use of DOACs
should based on multiple factors including the renal function.
 Bleeding is a common side effect of anticoagulants which can be treated and prevented .