Anticoagulation Anticoagulation Management in ACS Management in ACS

Patient with Bleeding RiskPatient with Bleeding Risk

Shanghai No.6th People’s Hospital

Department of Cardiology

Lu Zhigang

Case report

At admission

***, female, 86-years-old, WT 60kg 。 Admitted to hospital on Jun 9th 2010

because of persistent chest pain for 2 hours.

Prior history

Hypertension

OMI twice Cigarette smoking

At admission

BP 129/81mmHg at admission EKG ： atrial fibrillation, ST segment

depressed in I 、 II 、 V3-6 Cardiac enzyme: cTnI 1.61ug/L,

CKMB 7.9ug/L Blood routine: Hb 100g/L,Hct 28.3%,

plt 108*10^9/L renal function: Scr 116umol/L Diagnosis: ACS

Treatment

Aspirin 0.1 qd po Clopidogrel 75mg qd po Nadroparin 4100u iH q12hr until Jun 17 NS 250mL+ Salvianolate 0.2 / ivgtt qd Refused to coronary intervention

Course in hospital Before draw on Jun 17th complaint of tenderness in the right chest On Jun 17th morning a Φ6cm mass was palpated in the right lateral breast,

which was hard, tenderness and no flare On the afternoon of Jun 17th

ecchymosis was seen in the right lateral breast and right armpit with tenderness and no fluctuation

soft tissues in the right chest was swelling On Jun 18th morning hematoma was seen in the same area

Spontaneous subcutaneous hemorrhageSpontaneous subcutaneous hemorrhage

Changes of blood routine

Time Hb (g/L) Hct (%) WBC (*10^9/L)

Plt (*10^9/L)

Jun 9th 100 28.3 5.6 108

Jun 17th 9:00 89 25.6 3.9 124

Jun 17th 20:30 75 22.4 6.3 131

Jun 18th 6:00 63 18 7.8 136

Jun 21st 9:00 55 15.7 6.3 153

Risk

bleeding

Benefit

Thrombosis

Net profits

of anticoagulation ????

Relation between bleeding and mortality in ACS patients

Changes in recent 20 years about ACS Changes in recent 20 years about ACS anticoagulationanticoagulation

16-20% 12-15% 8-12% 6-10% 4-8%De

ath

/ M

I

1988ASA

1992ASA+

Heparin

1998 ASA+

Heparin+Anti-

GPIIB/IIIA

2003ASA+

LMWH +Clopidogrel +Intervention

With permission from Christopher Cannon

< 1988

bleedingbleeding

Major bleeding rates in studysP

ati

en

ts p

erc

enta

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Pa

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Rao SV, et al. European Heart Journal 2007;28:1193-1204

GRACE ：major bleeding increased death rates in ACS patients

Moscucci M et, et al.et al. Eur Heart J 2003;24:1815-1823

In-h

os

pital d

ea

th

In-h

os

pital d

ea

th

(%)

(%)

****

********

******p<0.001

overalloverall UAUA NSTEMINSTEMI STEMISTEMI

30 day death according to bleeding (OASIS Registry , OASIS-2, CURE)

John W. Eikelboom, et al.John W. Eikelboom, et al. Circulation 2006;114: 774 - 782Circulation 2006;114: 774 - 782

5 fold 5 fold risk risk

P<0.0001P<0.0001

bleedingbleeding

No bleedingNo bleeding30

da

y d

eat

h (

% )

30

da

y d

eat

h (

% )

3367633676 3341933419 3315733157 3299032990 3287932879 3276932769 3271032710

470470 459459 440440 430430 420420 410410 408408

(days) (days) No.No.

No bleedingNo bleeding

bleedingbleeding

N=34146 N=34146

Increased mortality at Days 180 in patients with bleeding

Rao et al. Am J Cardiol 2005;96:1200-1206

26,452 ACS patients from GUSTO IIb, PURSUIT and PARAGON A&B study

mortality adjusted HR (95% CI)

No bleeding 5.2% (983/18,886) 1.0

Minor bleeding 6.3% (273/4358) 1.4 (1.2-1.6)

Moderate bleeding 9.9% (253/2566) 2.1 (1.8-2.4)

Severe bleeding 35.1% (107/305) 7.5 (6.1-9.3)

Hazard Ratio

GUSTO bleeding

-5 1 5 1510

The Risk Factors of Bleeding

MMultivariate model for bleeding in patients with ACSultivariate model for bleeding in patients with ACS

MMultivariate model for bleeding in patients with ACSultivariate model for bleeding in patients with ACS

variablevariable Adjusted ORAdjusted OR P valueP value

Age (per 10y Age (per 10y

increase)increase)

1.281.28 <0.0001<0.0001

Female sexFemale sex 1.431.43 <0.0001<0.0001

History of renal History of renal

insufficiencyinsufficiency

1.481.48 0.00040.0004

History of bleedingHistory of bleeding 2.832.83 <0.0001<0.0001

GP IIb/IIIa blockersGP IIb/IIIa blockers 1.931.93 <0.0001<0.0001

PCIPCI 1.631.63 <0.0001<0.0001

Moscucci M , et al. Eur Heart J 2003;24:1815-23Moscucci M , et al. Eur Heart J 2003;24:1815-23

8.57.9

0.8

7.3

3.8

5.9

0.9

4

0.9

6

0.4

1.8

0

5

10

15

severe moderate normal/minimally impaired

Death Death MIMI strokestroke Major bleedingMajor bleeding

* ** ** ** *

**

Pa

tien

t perc

en

tage

Pa

tien

t perc

en

tage

GRACE GRACE (n=11774)(n=11774) ：： bleeding rates and mortality increased in ACS patientsbleeding rates and mortality increased in ACS patients

with renal insufficientwith renal insufficient

*p<0.05, **p<0.0001

J J Santopinto, et al. Heart 2003;89:1003-1008

CrCl and/or GFR should be calculated for every patient CrCl and/or GFR should be calculated for every patient

hospitalised for NSTE-ACS (I-B)hospitalised for NSTE-ACS (I-B) 。。 Elderly people, women Elderly people, women

and low body weight patients merit special attention as and low body weight patients merit special attention as

near normal serum creatinine level maybe associated with near normal serum creatinine level maybe associated with

lower than expected lower than expected CrCl and GFR level (I-B).CrCl and GFR level (I-B).

In patients with CrCl<30 ml/min or GFR <30 ml/min/1.73m²In patients with CrCl<30 ml/min or GFR <30 ml/min/1.73m², ,

a careful approach to the use of anticoagulants is a careful approach to the use of anticoagulants is

recommended recommended (I-C)(I-C)

… … … …

Recommendations for patients Recommendations for patients with CKDwith CKD

ESC Guidelines for the Mangement of NSTE-ACSESC Guidelines for the Mangement of NSTE-ACS

Assessment of bleeding risk is an important Assessment of bleeding risk is an important

component of the decision making component of the decision making

process…(I-B)process…(I-B)

Recommendations for bleeding Recommendations for bleeding complicationscomplications

ESC Guidelines for the Mangement of NSTE-ACSESC Guidelines for the Mangement of NSTE-ACS

Risk factors of ischemic Risk factors of ischemic eventsevents

ACS recently happenedACS recently happened PCI recently performedPCI recently performed reoccurred ACS after

stopping OAT LVEF<30% Diabetes Diabetes Multi coronary disease Stent length >25mmStent length >25mm Vessels diameter <2.5mmVessels diameter <2.5mm Incomplete

revascularizationevascularization Arterial sclerosis lesions >2Arterial sclerosis lesions >2

Risk factors of Risk factors of hemorrhage eventshemorrhage events

Past history of Past history of hemorrhagehemorrhage

Recurrent hemorrhagic Recurrent hemorrhagic ulcerulcer

Intracranial operationIntracranial operation Transurethral Transurethral

prostatectomyprostatectomy Extensive dissociated Extensive dissociated

operationoperation

Essential risk Essential risk factorsfactors

Elders Female Fat Heart failure Renal

insufficient Comorbidities

AntiAnti

coagulationcoagulation

In our case

Ccr = [(140-age) * weight (kg)] / [0.818×Scr (umol/L)] *0.85 (female)

= [(140-86) * 60 (kg)] / [0.818×116 (umol/L)] *0.85 (female)

= 29.1mL/min

CRUSADE bleeding score

Predictor Scores

Baseline Hct ， % 　

<31 9

31-33.9 7

34-36.9 3

37-39.9 2

≥40 0

CrCl: mL/min 　

≤15 39

>15-30 35

>30-60 28

>60-90 17

>90-120 7

>120 0

Heart rate ， bpm 　

≤70 0

71-80 1

81-90 3

91-100 6

101-110 8

111-120 10

≥121 11

Predictor Scores

sex 　

Male 0

Female 8

Signs of CHF on admission

　

No 0

Yes 7

Prior vascular disease 　

No 0

Yes 6

DM 　

No 0

Yes 6

SBP on admission, mmHg

　

≤90 10

91-100 8

101-120 5

121-180 1

181-200 3

≥201 5

Subherwal S,et al. Circulation. 2009;119:1873-82

Hamorrhage risk CRUSADE scores

High-low risk ≤20

Low risk 21-30

Moderate risk 31-40

High risk 41-50

Extremely high risk

≥50

Hct: 28.3 9

CrCl: 29.1 35

HR: 60 0

Sex: F 8

CHF: N 0

Prior history: Y 6

DM: N 0

SBP: 129 1

Score: 59

SummarySummary　　

Prevention of bleeding events is equally as

important as prevention of ischemic events

Risk of bleeding is associated with age, sex,

weight and CrCl etc

Bleeding carries a high risk of death, MI and

stroke

Risk stratification for bleeding should be part of

the decision making process

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