1. trong phòng ngừa đột quỵ thứ phát
Bs Mã Lệ Quân
11/04/2023

2. Nội dung
• Tổng quan
• Thuốc kháng đông đường uống trong phòng ngừa đột quỵ tái phát
• Warfarin, Acenocoumarol
• Kháng đông đường uống tác động trực tiếp – DOACs
• Nghiên cứu DOACs-Warfarin
• Chú ý khi sử dụng OACs
• Guideline AHA 2021
• Kháng đông trong phòng ngừa một số bệnh khác
• Kết luận

3. Case lâm sàng Nam 40t, nhập viện vì liệt nửa người trái.
NIHSS 12 (vận nhãn 1; tay T 4; chân T 4; mặt
2; nói khó 1) giờ thứ 4
TC: BTTMCB, RLLM, ĐTĐ, THA đang điều trị.

5. Giờ thứ 36
Giờ thứ 6

6. Transformation HI1
TSH 0.002 uIU/ml
T4 66.47pmol/L
Siêu âm tim
Dãn nhĩ trái (RV/LV #48mm)
EF 54%
Giảm động thành dưới vách, thành dưới
Hở 2 lá 2.5/4; type IIA2-IIIAP
Hở ba lá ¾
Tăng áp ĐMP PAP 47mmHg
Giờ thứ 50

7. 90% bệnh nhân đột quỵ thiếu máu do
huyết khối là từ tiểu nhĩ trái  huyết khối
đỏ  dùng kháng đông.
Trong nhóm bệnh tim gây lấp mạch, RN
chiếm 50% các trường hợp.
Fareed Moses S. Collado ET COL, JAHA, November 2, 2021, Vol 10, Issue 21
W. Dudley Johnson ET COL, European Journal of Cardio-Thoracic Surgery, Volume 17, Issue 6, June 2000, Pages 718–722
TS Nguyễn Bá Thắng, Giáo trinh Thần kinh học, 2020, trang 121

8. NGUY CƠ CỦA RUNG NHĨ
• Nguy cơ đột quỵ gấp 4-5 lần.
• Nguy cơ suy tim gấp 3-4 lần.
• Tăng nguy cơ tử vong và tàn phế.

9. Journal of Arrhythmia, Volume: 37, Issue: 6, Pages: 1389-1426

10. Atrial fibrillation as an independent risk
factor for stroke: the Framingham Study.
Abstract
The impact of nonrheumatic atrial fibrillation, hypertension, coronary heart disease, and cardiac
failure on stroke incidence was examined in 5,070 participants in the Framingham Study after 34
years of follow-up. There was a more thanCompared with subjects free of these conditions, the
age-adjusted incidence of stroke was more than doubled in the presence of coronary heart disease
(p less than 0.001) and more than trebled in the presence of hypertension (p less than 0.001).
fourfold excess of stroke in subjects with cardiac failure (p less than 0.001) and a near fivefold
excess when atrial fibrillation was present (p less than 0.001). In persons with coronary heart
disease or cardiac failure, atrial fibrillation doubled the stroke risk in men and trebled the risk in
women. With increasing age the effects of hypertension, coronary heart disease, and cardiac failure
on the risk of stroke became progressively weaker (p less than 0.05). Advancing age, however, did
not reduce the significant impact of atrial fibrillation. For persons aged 80-89 years, atrial fibrillation
was the sole cardiovascular condition to exert an independent effect on stroke incidence (p less
than 0.001). The attributable risk of stroke for all cardiovascular contributors decreased with age
except for atrial fibrillation, for which the attributable risk increased significantly (p less than 0.01),
rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years. While these
findings highlight the impact of each cardiovascular condition on the risk of stroke, the data suggest
that the elderly are particularly vulnerable to stroke when atrial fibrillation is present
P A Wolf et al, Stroke. 1991;22:983–988

11. Carmine Marini et al, Stroke, June 2005 Vol 36, Issue 6
Ước tính đột quỵ
tái phát ở BN
có/không có RN
Dân số Ý

12. Đánh giá nguy cơ đột quỵ ở BN RN
2001

13. Craig T. January et al, December 2, 2014 Vol 130, Issue 23

14. 2014 AHA
Guideline for the
Management of Patients
With Atrial Fibrillation
Craig T. January et al, December 2, 2014 Vol 130, Issue 23
- CHA2DS2-VASc score
recommended to assess stroke risk
- Warfarin recommended for
mechanical heart valves and target
INR intensity based on type and
location of prosthesis
- With prior stroke, TIA or CHA2DS2-
VASc score 2, OACs
recommended. Option include:
Warfarin, Dabi, Riva, Api

15. Eur Heart J, Volume 37, Issue 38, 7 October 2016, Pages 2893–2962,
2016
Stroke prevention in
atrial fibrillation.

16. Eur Heart J, Volume 42, Issue 5, 1 February 2021, Pages 373–498
2020 ESC Guidelines for the
diagnosis and management of
atrial fibrillation

17. Kháng đông đường uống Warfarin, Acenocoumarol
Cơ chế:
• Ức chế sự tổng hợp yếu tố đông máu lệ thuộc Vitamin K: II, VII, IX, X
• Điều hoà Protein C và Protein S.
Chỉ định:
• NMCT cấp kèm rung nhĩ, suy tim nặng, huyết khối trong buồng tim.
• DVT, PE
• Rung nhĩ do van hoặc không do van tim
• Tăng áp động mạch phổi nguyên phát
• Sau thay van tim nhân tạo (giữ mức INR 2.5-3.5)
• Phòng ngừa đột quỵ tái phát cho BN RN

18. Chống chỉ định
• Xuất huyết đang hoạt động, có ý nghĩa trên lâm sàng
• Giảm tiểu cầu < 50k
• Chấn thương nặng
• Xuất huyết nội sọ
• Thủ thuật xâm lấn hoặc chuyển dạ
• U nội sọ, u tuỷ sống
• Gây tê tuỷ sống
• Tăng huyết áp cấp cứu

19. Hạn chế
1. Cửa sổ điều trị hẹp
2. Đặc tính dược động học khó kiểm soát
3. Tương tác nhiều thuốc và thực phẩm
4. Khởi phát và chấm dứt tác dụng chậm

20. AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation, Volume: 123, Issue: 10, Pages: e269-e367,
VKA và xuất huyết nội sọ

21. Quá liều Warfarin và hướng xử trí
Tăng INR, không xuất huyết
• INR<5: ngưng hoặc giảm liều, điều chỉnh lại liều thấp hơn để đạt 2-3
• 5-9 Ngưng Warfarin và Vitamin K1 uống
• >9 Ngưng VKA, cho 5-10mg Vitamin K uống, theo dõi sát INR
Tăng INR kèm xuất huyết
• Truyền 10mg Vitamin K trong 30 phút và truyền huyết tương tươi đông lạnh với liều 15ml/kg.
• Đánh giá hiệu quả của Warfarin dựa trên INR.
• DVT gây PE, RN có nguy cơ thuyên tắc, giữ INR 2-3. Người Châu Á nên giữ ở mức thấp.
Tương tác thuốc:
• Agonist: Allopurinol, Amiodarone, Cephalosporin, Metronidazole và Bactrim.
• Antagonist: Barbiturate, Phenytoin (qua cơ chế làm thoái giáng và chuyển hoá ở gan)
• Tăng nguy cơ xuất huyết khi kết hợp với các thuốc chống kết tập tiểu cầu, kháng viêm, NSAIDs.

22. Vấn đề lựa chọn thuốc
1. Requirements of new antithrombotic agents
2. At least as effective as warfarin
3. Predictable response
4. Wide therapeutic window
5. Low incidence and severity of adverse effects
6. Oral fixed dose
7. No need for routine anticoagulation monitoring
8. Low potential for food or drud interactions
9. Fast onset and offset of action
10. Cost-effective
Gregory Y.H. Lip, European Heart Journal Supplements, Volume 7, Issue suppl_E, June 2005, Pages E21-E25

23. James C. Fredenburgh et al, J of thrombosis and haemostasis, Vol19, Issue1 January 2021 p20-29
 tổn thương Gan nặng
Tđ trên Thrombin
KT đơn dòng
ƯC YT Xa
ƯC YT XI
Dwight D. Eisenhower

25. NOACs
DOACs

26. Gregory Y.H. Lip et al, Stroke, December 2018
Vol 49, Issue 12

27. Drug Increase Anticoagulant Effects Decrease Anticoagulant Effects
Warfarin
Amiodarone, fluconazole,
tigecycline, voriconazole,
fluoroquinolones, verapamil,
diltiazem, other anticoagulants,
antiplatelet drugs, NSAIDs, and
SSRIs
Rifampin, phenobarbital,
carbamazepine, cigarette smoking
Dabigatran
Amiodarone, verapamil,
ketoconazole, dronaderone,
clopidogrel, enoxaparin, other
anticoagulants, antiplatelet drugs
Rifampin
Apixaban
Ketoconazole, other
anticoagulants, antiplatelet drugs
Rifampin
Rivaroxaban
Other anticoagulants, antiplatelet
drugs, fluconazole, ketoconazole,
erythromycin, and clarithromycin
Rifampin, phenytoin,
carbamazepine, St. John’s Wort
Edoxaban
Other anticoagulants, antiplatelet
drugs,
Rifampin
Common drug-drug interactions of oral anticoagulants
Nishank Jain et al, Clin J Am Soc Nephrol. 2019 Feb 7; 14(2): 278–287.

29. A. John Camm et col,
Europace (2018) 20, 1–11

30. A.
John
Camm
et
col,
Europace
(2018)
20,
1–11

31. Background
Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases
the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.
Methods
In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to
receive, in a blinded fashion, fixed doses of dabigatran — 110 mg or 150 mg twice daily — or, in an unblinded
fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary
outcome was stroke or systemic embolism.
N Engl J Med 2009; 361 1139-1151

32. Inclusion criteria Exclusion criteria
1. Previous stroke or transient ischemic
attack
2. Left ventricular ejection fraction of less
than 40%, NYHA class II or higher heart-
failure symptoms within 6 months before
screening
3.  75 years old
4. 65 - 74 years plus diabetes mellitus,
hypertension, or coronary artery disease.
1. Severe heart-valve disorder
2. Stroke within 14 days or severe stroke
within 6 months before screening,
3. Increased the risk of hemorrhage,
4. GFR <30 ml/min
5. Active liver disease
6. Pregnancy

33. Results
• Rates of the primary outcome were 1.69% per year in the warfarin group, as
compared with 1.53% per year in the group that received 110 mg of dabigatran
(relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11;
P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg
of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority).
• The rate of major bleeding was 3.36% per year in the warfarin group, as
compared with 2.71% per year in the group receiving 110 mg of dabigatran
(P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran
(P=0.31).
• The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as
compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10%
per year with 150 mg of dabigatran (P<0.001).
• The mortality rate was 4.13% per year in the warfarin group, as compared with
3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150
mg of dabigatran (P=0.051).
N Engl J Med 2009; 361 1139-1151

34. Conclusions
In patients with atrial fibrillation, dabigatran given at a dose of 110 mg
was associated with rates of stroke and systemic embolism that were
similar to those associated with warfarin, as well as lower rates of
major hemorrhage.
Dabigatran administered at a dose of 150 mg, as compared with
warfarin, was associated with lower rates of stroke and systemic
embolism but similar rates of major hemorrhage.
N Engl J Med 2009; 361 1139-1151

35. Rankin scale (on which scores
can range from 0 [no neurologic
disability] to 5 [severe disability],
with 6 indicating a fatal stroke)
was used to categorize stroke:
nondisabling stroke was defined
by a score of 0 to 2, and disabling
or fatal stroke, a score of 3 to 6.
N Engl J Med 2009; 361 1139-1151

36. N Engl J Med 2009; 361 1139-1151

37. Engl J Med 2011; 365 883-891
Background
The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent
monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and
predictable anticoagulation than warfarin.
Methods
In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were
at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted
warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was
noninferior to warfarin for the primary end point of stroke or systemic embolism.

38. Inclusion criteria Exclusion criteria
1. Nonvalvular atrial fibrillation, as documented on
electrocardiography, who were at moderate-to-
high risk for stroke.
2. Elevated risk was indicated by a history of stroke,
transient ischemic attack, 2 CHADS2 score
1. No previous ischemic stroke,
transient ischemic attack, or systemic embolism
2. <2 risk factors, CHADS2 score

39. Results
The primary end point occurred in 188 patients in the rivaroxaban group
(1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard
ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to
0.96; P<0.001 for noninferiority).
In the intention-to-treat analysis, the primary end point occurred in 269
patients in the rivaroxaban group (2.1% per year) and in 306 patients in the
warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03;
P<0.001 for noninferiority; P=0.12 for superiority).
Major and nonmajor clinically relevant bleeding occurred in 1475 patients in
the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group
(14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with
significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02)
and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
Engl J Med 2011; 365 883-891

40. Conclusions
In patients with atrial fibrillation, rivaroxaban was noninferior to
warfarin for the prevention of stroke or systemic embolism.
There was no significant between-group difference in the risk of major
bleeding, although intracranial and fatal bleeding occurred less
frequently in the rivaroxaban group.
Engl J Med 2011; 365 883-891

41. Engl J Med 2011; 365 883-891

42. Engl J Med 2011; 365 883-891
Cumulative Rates of the Primary End Point (Stroke or SystemicEmbolism) in the Per-
Protocol Population and in the Intention-to-Treat population.

43. Cumulative Rates of the Primary End Point during Treatment and after Discontinuation in
the Intention-to-Treat Population.
Engl J Med 2011; 365 883-891

44. Engl J Med 2011; 365 883-891

45. Background
Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations.
Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in
comparison with aspirin.
Methods
In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target
international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk
factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was
designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary
outcome and to the rates of major bleeding and death from any cause.
Engl J Med 2011; 365 981-992

46. Inclusion criteria Exclusion criteria
1. atrial fibrillation or flutter at
enrollment or two or more episodes of atrial
fibrillation or flutter, as documented by
electrocardiography, at least 2 weeks apart in the
12 months before enrollment.
2. In addition, at least one of the following risk
factors for stroke was required: an age of at least
75 years; previous stroke, transient ischemic
attack, or systemic embolism; symptomatic heart
failure within the previous 3 months or left
ventricular ejection fraction of no more than 40%;
diabetes mellitus; or hypertension requiring
pharmacologic treatment.
1. AF due to a reversible cause, moderate or severe
mitral stenosis, conditions other than atrial
fibrillation that required anticoagulation (e.g., a
prosthetic heart valve),
2. Stroke within the previous 7 days, a need for
aspirin at a dose of >165 mg a day or for both
aspirin and clopidogrel
3. severe renal insufficiency (serum creatinine level
of >2.5 mg per deciliter [221 µmol per liter] or
GFR <25 ml per minute).
4. 7 Patients were classified as not having received
warfarin previously if they had used warfarin or
another vitamin K antagonist for no more than 30
consecutive days.

47. Results
The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per
year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio
with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01
for superiority).
The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per
year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death
from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99;
P=0.047).
The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47%
per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001),
and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and
1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42).
Conclusions
In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke
or systemic embolism, caused less bleeding, and resulted in lower mortality.
Engl J Med 2011; 365 981-992

48. Engl J Med 2011; 365 981-992

49. Engl J Med 2011; 365 981-992
Kaplan–Meier Curves for the Primary Efficacy and Safety Outcomes
The primary efficacy outcome (Panel A) was stroke or systemic embolism.The primary safety outcome (Panel B) was
major bleeding, as defined accord-ing to the criteria of the International Society on Thrombosis and Haemo-stasis. The
inset in each panel shows the same data on an enlarged segmentof the y axis.

51. Engl J Med 2011; 365 981-992

52. N Engl J Med 2013; 369 2093-2104
The Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in
Myocardial Infarction 48 (ENGAGE AF-TIMI 48)
BACKGROUND
Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy
and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known.
METHODS
We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of
edoxaban with warfarin in 21,105 patients with moderateto-high-risk atrial fibrillation (median follow-
up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban
regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end
point was major bleeding.

53. Inclusion criteria Exclusion criteria
1. 21 years old + AF documented by means of
an electrical tracing within the 12 months
preceding randomization,
2. CHADS score  2
3. and anticoagulation therapy planned for the
duration of the trial.
1. AF due to a reversible disorder;
2. GFR < 30 ml/min;
3. High risk of bleeding;
4. Dual antiplatelet therapy;
5. Moderate-severe mitral stenosis; other
indications for anticoagulation therapy;
6. Acute coronary syndromes, coronary
revascularization, or stroke within 30
days before randomization;
7. Inability to adhere to study procedures

54. RESULTS
The annualized rate of the primary end point during treatment was 1.50% with warfarin (median
time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard
ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with
low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority).
In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin
(hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose
edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10).
The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with highdose
edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban
(hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001).
The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74%
(hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96;
P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke,
systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio,
0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32).
N Engl J Med 2013; 369 2093-2104

55. CONCLUSIONS
Both once-daily regimens of edoxaban were noninferior to warfarin
with respect to the prevention of stroke or systemic embolism
and were associated with significantly lower rates of bleeding and
death from cardiovascular causes.
N Engl J Med 2013; 369 2093-2104

56. N Engl J Med 2013; 369 2093-2104

57. N Engl J Med 2013; 369 2093-2104
Kaplan–Meier Curves for the Primary Efficacy and Principal SafetyEnd Points.
Panel A shows the cumulative event rates for stroke or systemic embolismin the intention-to-treat population (all patients who underwent
random-ization) during the overall study period (i.e., beginning from the time ofrandomization to the end of the double-blind treatment
period); data fromthe overall study period, rather than the treatment period only, were usedin the superiority analyses of efficacy. Panel B
shows the principal safetyoutcome of major bleeding, defined according to the criteria of the Inter-national Society on Thrombosis and
Haemostasis,10in the safety popula-tion during the treatment period. The Kaplan–Meier curve was drawn with-out interval censoring for
treatment interruptions. The inset in each panelshows the same data on an enlarged segment of the y axis.

58. N Engl J Med 2013;
369 2093-2104

59. Một số lưu ý khi sử dụng OACs
1. Đánh giá nguy cơ xuất huyết
2. Thời điểm sử dụng kháng đông
3. Chuyển đổi VKA  DOACs

60. Thang đánh giá nguy cơ xuất huyết
ORBIT
ATRIA
HAS‐BLED

61. ORBIT BLEEDING SCORE
Variable Score
Hemoglobin <13g/dL or Hct <40% for males
Hemoglobin <12g/dL or Hct <36% for females
2
>74 years 1
Bleeding history (any history of GI, ICH or hemorrhage
stroke)
2
eGFR <60ml/min/1.73m2 1
Treatment with antiplatelet agents 1
Total ORBIT score 7
0 - 2  LOW
3  MEDIUM
4-7  HIGH

62. ATRIA SCORE

63. 0 – LOW RISK
1 – 2 – MODERATE
3 – HIGH RISK
HAS-BLED SCORE

64. Performance of the HAS‐BLED, ORBIT, and ATRIA Bleeding Risk Scores
on a Cohort of 399344 Hospitalized Patients With Atrial Fibrillation
and Cancer: Data From the French National Hospital Discharge
Database
Background
• The association between cancer types and specific bleeding events in patients with atrial fibrillation has been scarcely
investigated. Also, the performance of bleeding risk scores in this high‐risk subgroup of patients is unclear. We investigated the
rate of any bleeding, intracranial hemorrhage, major bleeding, and gastrointestinal bleeding according to cancer types in patients
with atrial fibrillation. We also tested the predictive value of HAS‐BLED, ATRIA, and ORBIT bleeding risk scores.
Methods and Results
• Observational retrospective cohort study including hospitalized patients with atrial fibrillation and cancer from the French National
Hospital Discharge Database (Programme de Medicalisation des Systemes d'Information) from January 2010 to December
2019. Major bleeding was defined according to Bleeding Academic Research Consortium definitions. Patients with HAS‐BLED
≥3, ATRIA ≥5, or ORBIT ≥4 were classified as at high bleeding risk. Receiver operating characteristic analysis for each score
against any bleeding, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage was performed. Areas under the
curve (AUCs) were then compared. We included 399 344 patients. Mean age was 77.9±10.2 years, and 63.2% were men. The
highest intracranial hemorrhage rates were found in leukemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver
(1.45%/year), and pancreas cancer (1.41%/year). Receiver operating characteristic analysis showed that ORBIT score predicted
best for any bleeding. In addition, ORBIT score ≥4 had the highest predictivity for major bleeding (AUC, 0.805), followed by
HAS‐BLED ≥3 and ATRIA ≥5 (AUCs, 0.716 and 0.700, respectively). HAS‐BLED and ORBIT performed best for intracranial
hemorrhage (AUCs, 0.744 and 0.742 for continuous scores, respectively), better than ATRIA (AUC, 0.635). For
gastrointestinal bleeding, ORBIT ≥4 had the highest predictivity (AUC, 0.756), followed by the HAS‐BLED ≥3 (AUC, 0.702)
and ATRIA ≥5 (AUC, 0.662).
Daniele Pastori et al, JAHA, December 6, 2022 Vol 11, Issue 23

65. European Heart Journal, Volume 37, Issue 38, 7
October 2016, Pages 2893–2962,
2016
ESC
Thời điểm sử dụng
kháng đông

66. Shunsuke Kimura. Stroke. Practical “1-2-3-4-
Day” Rule for Starting Direct Oral Anticoagulants
After Ischemic Stroke With Atrial Fibrillation:,
2022, Volume: 53, Issue: 5, Pages: 1540-1549
2022

67. Transformation HI1
TSH 0.002 uIU/ml
T4 66.47pmol/L
Siêu âm tim
Dãn nhĩ trái (RV/LV #48mm)
EF 54%
Giảm động thành dưới vách, thành dưới
Hở 2 lá 2.5/4; type IIA2-IIIAP
Hở ba lá ¾
Tăng áp ĐMP PAP 47mmHg
Giờ thứ 50

68. Thời điểm dùng OACs
lại sau biến cố xuất
huyết não?
European Heart Journal, Volume 37, Issue 38, 7
October 2016, Pages 2893–2962

69. Twitching
2021 European
Heart Rhythm
Association
Practical Guide on
the Use of Non-
Vitamin K
Antagonist Oral
Anticoagulants in
Patients with
Atrial Fibrillation
Hein Heidbuchel et al, EP Europace, Volume 23, Issue 10, October 2021, Pages 1612–1676

71. Một số đặc điểm xem xét khi dùng DOACs
1. Suy thận
2. Suy gan
3. Lớn tuổi
4. Nhẹ cân

72. Suy thận

73. Europace, Volume 23, Issue 10, October 2021, Pages 1612–1676
Use of NOACs according to renal function
(Summary of product characteristics)

74. Eur Heart J, Volume 33, Issue 22, November 2012, Pages 2821–2830

75. Lai‐Chu See. Journal of the American Heart Association.
Effectiveness and Safety of Non–Vitamin K Antagonist Oral
Anticoagulant and Warfarin in Cirrhotic Patients With Nonvalvular
Atrial Fibrillation, Volume: 8, Issue: 5, DOI:
(10.1161/JAHA.118.011112) Copyright © 2019 The Authors. Published on behalf of the
American Heart Association, Inc., by Wiley Blackwell
Cirrhosis

76. Lai‐Chu See. Journal of the American Heart Association.
Effectiveness and Safety of Non–Vitamin K Antagonist Oral
Anticoagulant and Warfarin in Cirrhotic Patients With
Nonvalvular Atrial Fibrillation, Volume: 8, Issue: 5, DOI:
(10.1161/JAHA.118.011112)
Copyright © 2019 The Authors. Published on behalf of the
American Heart Association, Inc., by Wiley Blackwell

77. J. Steffel et al, The 2018 European Heart Rhythm Association Practical Guide on the use of NOACs in patients with AF., European heart journal, 2018
Calculation of the Child-Turcotte-Pugh score and use of NOACs in hepatic insufficiency

78. Direct OACs in Patients With
Nonvalvular AF
and Low Body Weight
<50kg #30%
So-Ryoung Lee et col, Journal of the American College of Cardiology Volume 73, Issue 8, 5 March 2019, Pages 919-931

79. So-Ryoung Lee et col, Journal of the
American College of Cardiology Volume
73, Issue 8, 5 March 2019, Pages 919-931

80. So-Ryoung
Lee
et
col,
Journal
of
the
American
College
of
Cardiology
Volume
73,
Issue
8,
5
March
2019,
Pages
919-931

82. European Heart Journal (2020) 00, 1125

83. Choosing the right drug to
fit the patient when
selecting oral
anticoagulation for stroke
prevention in AF
A. M. Shields et al, Journal of Internal Medicine, 2015, Volume: 278, Issue: 1, Pages: 1-18
The SAMeTT2R2 Score
Sex – female 1
Age <60 1
Medical
history (>2
comorbidities)
1
Treatment
(interacting
drugs)
1 e.g.
amiodarone
Tobacco use 2 Any current
smoking
Race (ethnic
minority)
2
Total 8

84. RELY
2009
ROCKET
AF
2010
ARISTOTLE
2011
ENGAGE
AF-TIMI
48
2013
NOW ?

86. Stroke.2021;52:e364–e467.

88. Recommended antithrombotic
regimen in patients with
history of ischemic stroke or
TIA
and different valvular heart
disease conditions
Stroke.2021;52:e364–e467.
AF, atrial fibrillation; AV, aortic valve; AVD, aortic valve disease; DOAC, direct oral anticoagulant; MAC, mitral annular calcification; MS, mitral stenosis; MV,
mitral valve; MVD, mitral valve disease; MVP, mitral valve prolapse; and VHD, valvular heart disease. *Definition of valvular AF. †Includes MAC and MVP.
‡Rheumatic and nonrheumatic AVD. §Increase the target international normalized ratio by 0.5, depending on bleeding risk

89. Anticoagulant therapy for patients with cardiomyopathy,
ischemic stroke, or transient ischemic attack (TIA) in sinus
rhythm.
LVAD, left ventricular assist device

91. - Embolic Stroke of Undetermined
Source

92. Các chỉ định khác
Huyết khối tĩnh mạch nội sọ
• Dùng Kháng đông tiêm Heparin LMWH, sau đó là VKA.
• Ít nhất 6 tháng.
• Nếu BL tăng đông tiến triển thì dài hơn.
Phòng ngừa huyết khối tĩnh mạch sau ĐQ

93. Khuyến
cáo
về
chẩn
đoán,
điều
trị
và
dự
phòng
thuyên
tắc
huyết
khối
tĩnh
mạch
2016
Hội
Tim
mạch
Việt
Nam
20 33

94. Một số trường hợp đặc biệt:
- BN điều trị tại khoa Hồi sức tích cực: do có nhiều YTNC
thuyên tắc HKTM phối hợp nên được dự phòng một cách
hệ thống bằng Heparin TLPT thấp hoặc Heparin không
phân đoạn, trừ trường hợp nguy cơ chảy máu cao: dự
phòng bằng máy bơm hơi áp lực ngắt quãng (IIC).
- BN đột quỵ cấp do tắc mạch: Khuyến cáo dự phòng bằng
máy bơm hơi áp lực từng lúc với BN nhập viện trong
vòng 72 giờ kể từ khi bắt đầu triệu chứng, và có liệt vận
động. Xem xét dự phòng bằng thuốc chống đông có thể
bắt đầu sớm nhất là 48 giờ sau khi bị đột quỵ, và kéo dài
trong vòng 2 tuần, hoặc tới khi BN có thể vận động
(nhưng không quá 6 tuần).
- BN đột quỵ cấp do chảy máu não: Khuyến cáo dự phòng
bằng máy bơm hơi áp lực ngắt quãng ngay khi nhập
viện. Xem xét dự phòng bằng chống đông sớm nhất sau
3 ngày, sau khi đã cân nhắc kỹ nguy cơ chảy máu (dựa
vào lâm sàng, huyết áp, kích thước vùng chảy máu) và
nguy cơ tắc mạch (tình trạng bất động) đối với từng trường
hợp cụ thể.
Khuyến
cáo
về
chẩn
đoán,
điều
trị
và
dự
phòng
thuyên
tắc
huyết
khối
tĩnh
mạch
2016
Hội
Tim
mạch
Việt
Nam

95. Kết luận

96. Background and Purpose—Guideline adherent oral anticoagulant (OAC) management of patients with
nonvalvular atrial fibrillation has been associated with improved outcomes, but limited data are available from
Asia. We aimed to investigate outcomes in patients who received guideline compliant management compared
with those who were OAC undertreated or overtreated, in a large nationwide multicenter cohort of patients with
nonvalvular atrial fibrillation in Thailand.
Methods—Patients with nonvalvular atrial fibrillation were prospectively enrolled from 27 hospitals—all of which
are data
contributors to the COOL-AF Registry (Cohort of Antithrombotic Use and Optimal INR Level in Patients With
NonValvular Atrial Fibrillation in Thailand). Patients were categorized as follows: (1) guideline adherence group
when OAC was given in high-risk or intermediate-risk, but not in low-risk patients; (2) undertreatment group when
OAC was not given in the high-risk or intermediate-risk groups; and (3) overtreatment group when OAC was
given in the low-risk group or when OAC was given in combination with antiplatelets without indication.

97. Results
A total of 3327 patients who had follow-up clinical outcome data were
included. The mean age of patients was 67.4 years and 58.1% were
male. The numbers of patients in the guideline adherence group,
undertreatment group, and overtreatment group were 2267 (68.1%),
624 (18.8%), and 436 (13.1%) patients, respectively. The overall rate of
ischemic stroke, major bleeding, all bleeding, and death was 3.0%,
4.4%, 15.1%, and 7.8%, respectively. Undertreated patients had a
higher risk of ischemic stroke and death compared with guideline
adherent patients, and overtreated patients had a higher risk of
bleeding and death compared with OAC guideline-managed patients.
Rungroj Krittayaphong. Stroke, Volume: 51, Issue: 6, Pages: 1772-1780

98. Rungroj Krittayaphong. Stroke, Volume: 51, Issue: 6, Pages: 1772-1780

99. Conclusions
Adherence to OAC management guidelines is associated with
improved clinical outcomes in Asian nonvalvular atrial
fibrillation patients.
Undertreatment or overtreatment was found to be associated
with increased risk of adverse outcomes compared with
guideline-adherent management
Rungroj Krittayaphong. Stroke, Volume: 51, Issue: 6, Pages: 1772-1780