Challenging cases and risk assessment in clinical practice

1
Challenging cases and risk assessment in clinical
practice

• Christian Spaulding MD, PhD, FESC,
  FACCCardiology DepartmentCochin HospitalParis
  Descartes UniversityParis, France

2
Trends in ACS
180 160 140 120 100 80 60 40 20 0
19751978 19811984 19861988
19901991 19931995 1997
Incidence rate (per 100,000)
Q-wave
Non Q-wave
ACS acute coronary syndrome
Reprinted with permission Furman MI, et al. J Am
Coll Cardiol 200137157180
3
STEMI versus NSTEMI in-hospital versus
1-year-mortality
14 12 10 8 6 4 2 0
STEMI NSTEMI
plt0.01
plt0.01
Mortality ()
In-hospital mortality 1-year mortality
STEMI ST segment elevation myocardial
infarctionNSTEMI non-ST segment elevation
myocardial infarction
Adapted from Furman MI, et al. J Am Coll Cardiol
200137157180
4
STEMI versus NSTEMI mortality after discharge
1.0 0.98 0.96 0.94 0.92 0.90
STEMI
Survival (MI patients discharged alive)
NSTEMI
0 1 2 3 4 5 6 7 8 9 10 11 12
Months after discharge
Adapted from Furman MI, et al. J Am Coll
Cardiol 200137157180
MI myocardial infarction
5
OASIS-5 mortality at days 30/180 in patients
with major bleeds
0.2 0.15 0.1 0.05 0
Major bleed 9 days
Cumulative hazard
No major bleed 9 days
0 30 60 90 120 150 180
Days
Adapted from Yusuf S. N Engl J Med
2006354146476
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Treatment of NSTEMI a balancing act

• Clinical benefit of drugintervention

• Bleeding complications

7
The progression of antiplatelet therapy
Single antiplatelet therapy
Aspirin 25
100 80 60 40 20 0
Dual antiplatelettherapy
Aspirin clopidrogrel20
Higher IPA
Relative reduction in ischaemicevents
Aspirin prasugrel19
Relative increase in major bleeding
32
38
60
Placebo
APTC1
CURE2
TRITON-TIMI 383
1Antiplatelet Trialists Collaboration. BMJ
199430881106 2Yusuf S, et al. N Engl J Med
2001345494502 3Wiviott SD, et al. N Engl J Med
2007357200115
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A new concept was born

• Bleeding carries a high risk of death, MI and
  stroke
• Rate of major bleeding is as high as the rate of
  death at the acute phase of NSTE-ACS
• Prevention of bleeding is equally as important as
  prevention of ischaemic events and results in a
  significant risk reduction for death, MI and
  stroke
• Risk stratification for bleeding should be part
  of thedecision-making process

Bassand, JP et al. Eur Heart J 2007281598660
9
Risk factors for bleeding the GRACE registry
OR odds ratio CI confidence interval GP
glycoprotein PCI percutaneous coronary
intervention
Moscussi M, et al.Eur Heart J 200324181523
10
Non-CABG TIMI major bleeding in selected
subgroups of the TRITON TIMI 38 study
p value
p interaction
History of stroke or TIA
Yes
0.06

No
0.08
0.22
At least one of age ?75 years, body weight
lt60kg, or history stroke/TIA
Yes
0.10

No
0.17
0.64
0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6
.5
Hazard ratio (95 CI)
Clopidogrel better
Prasugrel better
Kaplan-Meier event estimates for patients
receiving ?1 dose, within 7 days of
discontinuation, or as determined locally to be
related Tests hazard ratio 1.0 within
subgroups Tests equality of hazard ratio
between subgroups TIA transit ischaemic attack
Adapted from Wiviott S, et al. NEJM
2007357200115
11
Any cause death, non-fatal MI, non-fatal stroke,
non-CABG TIMI major bleeding in selected
subgroups of the TRITON TIMI 38 study
p value
p interaction
History of stroke or TIA
Yes
0.04

No
lt0.001
0.006
Yes
0.43

At least one of age ?75 years, body weight
lt60kg, or history stroke/TIA
No
lt0.001
0.006
0.5 0.8 1.0 1.3 1.5 1.8 2.0 2.3 2.6
Hazard ratio (95 CI)
Clopidogrel better
Prasugrel better
Kaplan-Meier estimates intention-to-treat
cohort Tests hazard ratio 1.0 within
subgroups Tests equality of hazard ratio between
subgroups
Adapted from Wiviott S, et al. NEJM
2007357200115
12
A difficult decision on a rainy Sunday afternoon
in Paris

• Male, 78 years of age
• Past history
• diabetes treated by insulin
• haemorrhagic stroke with no sequellae 2 years ago
  
• medical treatment clopidogrel 75mg, atorvastatin
  10mg
• Chest pain on exertion for 2 weeks and at rest
  for 48 hours, lasting 20 minutes
• last chest pain 2 hours before admission
• Physical examination 1.58m, 48kg (BMI
  19.2kg/m2)
• ECG ST segment depression in leads V1V6
• Troponin 0.5 (normal lt0.004)
• Normal creatinine level

BMI body mass index ECG electrocardiogram
13

Is this patient at low, moderate or high risk for
ischaemic events?
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Is this patient at low, moderate or high risk
for bleeding complications?
15
A difficult decision on a rainy Sunday afternoon
in Paris

• High-risk for ischaemic events
• age
• diabetes
• ST segment depression in anterior leads
• elevated troponin
• High risk for bleeding complications
• age
• past history of haemorrhagic stroke
• BMI 19.2kg/m2

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A difficult decision on a rainy Sunday afternoon
in Paris

• Treatment
• aspirin 160mg followed by 100mg daily
• clopidogrel reloading dose of 600mg, 75mg daily
• LMWH fondaparinux 2.5mg daily
• atenolol 100mg daily
• atorvastatin 80mg

LMWH low molecular weight heparin
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Coronary angiogram
18
Coronary angiogram
19
Bare metal stent (2.75 x 15)
20
Two days later . . .
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Would you initiate a GP IIb/IIIa inhibitor?
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A difficult decision on a rainy Sunday afternoon
in Paris

• Because of the high risk profile for ischaemic
  events and bleeding complications, GP IIb/IIIa
  inhibitors were not administered and a coronary
  angiogram was performed 4 hours after admission
  via the radial artery

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What would you do?
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IVUS
Undersized stent (2.8mm RVD 3.5mm)
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Balloon inflation (3.5 X 12 at 22 atm)
Balloon 3.5 X 12 at 22atm
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Stent thrombosis
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Treatment of NSTEMI a balancing act

• Clinical benefit of a drug
• reduces mortality

• Bleeding complications
• increases mortality

• Careful patient selection
• age, gender, past history of bleeding, low
  weight, renal insufficiency