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BLEEDING AND ACUTE CORONARY SYNDROMES
Cardiac Catherization Conference
Syed Raza MD
Cardiology Fellow
VCU Medical Center
06/02/2011
Outline:
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Introduction- Classification of bleeding scales
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Risk factors

Prognostic implications
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Strategies to reduce bleeding
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Conclusion
Bleeding and ACS
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In patients with acute coronary syndromes, early treatment
with anti-thrombotic medications and catheter based
interventions reduced ischemic events but at an increased
risk of bleeding.
The reported incidence of bleeding after treatment for ACS
ranges from 1% to 10% and depends on a number of factors.
Bleeding is strongly associated with adverse outcomes in
patients with ACS. 2/3rd of patients bleed at access site.
Bleeding has been classified by different investigators using
different scales.
Bleeding Scales- Why?

Bleeding scale = Common language

Consistent reporting of bleeding events across different
populations, regions and trials.

Facilitate comparisons across different regions and
populations, treatment strategies and different data sets.
Popular Bleeding Scales

GUSTO

TIMI

ACUITY

REPLACE-2
GUSTO
Severe or life-threatening:
Intracranial or bleeding that causes hemodynamic compromise
and requires intervention.
Moderate:
Bleeding that requires blood transfusion but does not result in
hemodynamic compromise.
Mild:
Bleeding that does not meet criteria for either severe or
moderate bleeding.
TIMI
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Major:
Intracranial or ≥ 5 g/dl decrease in the hemoglobin
concentration or ≥ 15% decrease in HCT.
Minor:
Observed blood loss with ≥ 3 g/dl decrease in the Hgb
concentration or ≥ 10% decrease in HCT
Minimal:
All other bleeding
ACUITY
Major:
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Intracranial or intraocular bleeding
Access site bleeding requiring intervention
Hematoma ≥ 5 cm in diameter
Drop in Hgb ≥ 4 g/dl without overt source of bleeding or ≥ 3
g/dl with an overt source
Bleeding requiring reoperation or transfusion
Minor:

All other bleeding
Case 1

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70 y o F with CAD s/p PCI
with DES to LAD 6 months
ago
On aspirin 81 mg po daily
and plavix 75 mg po daily
Fell and brought to ED
Head CT shows a 2 x 3 cm
frontal intraparenchymal
hemorrhage

How do you classify her
bleeding?

GUSTO = Major

TIMI = Major

ACUITY = Major
Case 2
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58 y o male with NSTEMI
received DES to LAD
On ASA 325 mg po daily
and plavix 75 mg po daily
Bivalirudin given during PCI
Had hemetemesis with
Hgb drop from 13 g/dl to
10.5 g/dl (2.5 g/dl drop).
Vitals remained stable.
Received 1 unit of PRBCs
EGD- non-bleeding ulcer=
PPI Rx

How do you classify his
bleeding?

GUSTO = Moderate

TIMI = Minimal

ACUITY = Major
Bleeding Classifications

Clinical elements

Laboratory values

Response to bleeding

Optimal scale should probably have all the above
elements
Risk Factors Associated with Bleeding
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Older age
Female sex
Renal failure
History of bleeding
Use of GP IIb/IIIa use
Risk Factors For Bleeding- Evidence
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GRACE

ACUITY

CRUSADE
Risk Factors For Bleeding
GRACE
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24000 patients with ACS were studied.
Risk factors for bleeding were identified using logistic
regression analysis.
Major bleeding was defined as life-threatening bleeding
requiring transfusion of ≥ 2 units of PRBCs, or HCT decrease
of 10% or hemorrhagic/subdural hematoma.
Major bleeding occurred in 3.9% overall patients and:
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4.8 % with STEMI
4.7% with NSTEMI
2.3% with unstable angina
GRACE
Bleeding = Mortality
GRACE Registry Data
ACUITY
ACUITY
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> 13000 patients with ACS were randomized to:
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Heparin plus GPI
Bivalirudin plus GPI
Bivalirudin alone
3 primary outcomes (30 days):
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Composite ischemia
Major bleeding
Net clinical outcome
ACUITY
Independent Predictors of Major Bleeding
ACUITY
ACUITY
Independent predictors of mortality
ACUITY
CRUSADE
(Circulation. 2009;119:1873-1882.)
CRUSADE
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> 89000 patients with NSTEMI were studied.
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Developed and validated a model that identified 8
independent predictors of in-hospital mortality.
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Bleeding score (1-100) was created by assigning weighted
integers that corresponded to the coefficient of each variable.
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Rate of major bleeding increased by bleeding risk quintiles.
Circulation. 2009;119:1873-1882
CRUSADE
CRUSADE
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Very low 20 or less
Low 21-30
Moderate 31-40
High 41-50
Very high > 50
CRUSADE
CRUSADE
CRUSADE
Euro Heart Survey-ACS Data (STEMI)
Gitt et al. JACC 2010;55;A101.E945
Euro Heart Survey-ACS Data (NSTEMI)
Gitt et al. JACC 2010;55;A115.E1073
Bleeding
Mortality
BLEEDING = MORTALITY
BLEEDING = HIGH RISK PATIENTS = MORTALITY
BLEEDING=MORTALITY
Eikelboom et al Circulation. 2006;114:774-782
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Pooled analysis of > 34000 patients from OASIS, OASIS-2 and
CURE trial.
Major bleeding defined as that requiring > 2 units of PRBCs or
life-threatening >intracranial, Hgb drop of atleast 5 g/dl,
requiring surgical intervention. All other was minor.
Primary outcome was death during the first 30 days.
Also examined were the association between bleeding and
outcomes in subgroups and dose relation between bleeding
and death.
30 day mortality
Eikelboom et al Circulation. 2006;114:774-782
6 month mortality
Eikelboom et al Circulation. 2006;114:774-782
Dose relation
Eikelboom et al Circulation. 2006;114:774-782
Conclusions:
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Increase in mortality among patients who develop
major bleeding remains evident after adjustment
for baseline characteristics.
Mortality is greatest in first 30 days and is
markedly reduced if patients survive at least 30
days after a major bleed.
There appears to be a strong, consistent, temporal
and dose related association between major
bleeding and death.
Eikelboom et al Circulation. 2006;114:774-782
If bleeding kills…..
Can blood transfusion save lives?
Transfusion > Mortality
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24000 pts with ACS
analyzed from GUSTO IIb,
PURSUIT and PRAGON.
10% underwent
transfusion.
Transfusion was associated
with HR of 3.94 [CI 3.264.75] for death.
Predicted probability of 30
day death was higher with
transfusion at nadir HCT >
25%.
Rao et al. JAMA. 2004;292:1555-1562
Transfusion > Mortality
Doyle et al J Am Coll Cardiol 2009;53:2019–27
Older blood > higher mortality
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Red cell transfusion in
post-CABG and valve pts
was studied.
3000 pts were given old
blood (> 2 weeks) and
3000 pts were given new
blood (< 2 weeks).
At 1 year, mortality was
significantly less in pts
given new blood (7.4% vs
11%, p < 0.001).
Koch et al. N Engl J Med 2008;358:1229-39.
Possible mechanisms linking bleeding with increased mortality
Strategies to reduce bleeding

Assess bleeding risk
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Lower risk drugs
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Use of radial site for catherization
`
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About 17000 patients in ACUITY and HORIZON-AMI trial were
studied
Independent predictors of non-CABG related bleeding within
30 days were evaluated
Integer risk score for major bleeding within 30 days was
developed
Predictors of major bleeding
Integer risk score
Integer risk score
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< 10 = Low risk
10-14= Moderate
15-19= High
20 or more= Very
high
CRUSADE BLEEDING SCORE
www.crusadebleedingscore.org
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Very low 20 or less
Low 21-30
Moderate 31-40
High 41-50
Very high > 50
Drugs with lower bleeding risk
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Fondaparinux – OASIS-5
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Bivalirudin – HORIZON-AMI
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20, 000 patients randomized to enaxaparin or fondaparinux.
Thienopyridines and GP IIa/IIIb use at discretion of physician.
Outcomes measured: Efficacy, safety and net clinical outcome
of fondaparinux versus enoxaparin in patients with NSTE-ACS
treated with 1) GP IIb/IIIa 2) Thienopyridines
Jolly et al. JACC 2009;54;468-476
OASIS-5
OASIS-5
Jolly et al. JACC 2009;54;468-476
OASIS-5
Jolly et al. JACC 2009;54;468-476
OASIS-5 : Conclusions
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Ischemic events were similar between the groups.
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Major bleeding was reduced by 40% in
fondaparinux group compared with enoxaparin.
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Fondaparinux improved net clinical outcome.
Jolly et al. JACC 2009;54;468-476
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STEMI patients were randomized to receive either bivalirudin
or heparin plus a GP IIa/IIIb.
Patients were followed for 1 year.
2 primary endpoints:
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Major Bleeding
NACE (Major bleeding + MACE- death, re-infarction, TVR or CVA)
Mehran et al. Lancet 2009; 374: 1149–59
HORIZON-AMI
Mehran et al. Lancet 2009; 374: 1149–59
HORIZON-AMI
HORIZON-AMI : Conclusions
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In STEMI patients undergoing primary PCI,
anticoagulation with bivalirudin reduced net
adverse clinical events and major bleeding at 1
year compared with heparin plus GP IIb/IIIa.
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The rate of MACE was similar.
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Cardiac mortality and all-cause mortality at 1 year
was lower in bivalirudin group.
Jolly et al. Am Heart J 2009;157:132-40
Conclusions:

A strong association exists between bleeding and
higher mortality in patients with acute coronary
syndromes.

Key to improved patient outcomes:
 Identify
patients at high risk of bleeding.
 Institute strategies to lower bleeding while still
yielding a net clinical benefit for patients.
Thank you.
QUESTIONS AND ANSWERS