Challenging cases and risk assessment in clinical practice

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

Trends in ACS

Inci

den

ce r

ate

(per

100

,000

)

Q-wave Non Q-wave

1975–1978

1981–1984

1986–1988

1990–1991

1993–1995

1997

ACS = acute coronary syndrome Reprinted with permission: Furman MI, et al. J Am Coll Cardiol 2001;37:1571–80

180

160

140

120

100

80

60

40

20

0

STEMI versus NSTEMI in-hospital versus 1-year-mortality

Mo

rtal

ity

(%)

9.3

7.1

5.7

10.8p<0.01

p<0.01

STEMI = ST segment elevation myocardial infarctionNSTEMI = non-ST segment elevation myocardial infarction

Adapted from: Furman MI, et al. J Am Coll Cardiol 2001;37:1571–80

STEMI

NSTEMI

14

12

10

8

6

4

2

0In-hospital mortality 1-year mortality

Months after discharge

Su

rviv

al (

MI

pat

ien

ts

dis

char

ged

ali

ve)

STEMI versus NSTEMI mortality after discharge

0 1 2 3 4 5 6 7 8 9 10 11 12

1.0

0.98

0.96

0.94

0.92

0.90

STEMI

NSTEMI

Adapted from: Furman MI, et al. J Am Coll Cardiol 2001;37:1571–80MI = myocardial infarction

OASIS-5: mortality at days 30/180 in patients with major bleeds

Adapted from: Yusuf S. N Engl J Med 2006;354:1464–76

Major bleed 9 days

No major bleed 9 days

Days

Cu

mu

lati

ve h

azar

d

0.2

0.15

0.1

0.05

0 0 30 60 90 120 150 180

Treatment of NSTEMI: a balancing act

Clinical benefit of drugintervention

Bleeding complications

Single antiplatelet therapy

Dual antiplatelettherapy

Higher IPA

+ 60% + 38% + 32%

Relative reduction in

ischaemicevents

Relative increase

in major bleeding

The progression of antiplatelet therapy

100

80

60

40

20

0Placebo APTC1 CURE2 TRITON-TIMI 383

Aspirin–25%

Aspirin +clopidrogrel

–20% Aspirin +prasugrel

–19%

1Antiplatelet Trialists’ Collaboration. BMJ 1994;308:81–1062Yusuf S, et al. N Engl J Med 2001;345:494–502

3Wiviott SD, et al. N Engl J Med 2007;357:2001–15

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 2007;28:1598–660

Risk factors for bleeding: the GRACE registry

Adjusted OR 95% CI P-value

Age (per 10-year increase) 1.28 1.21–1.37 <0.0001

Female 1.43 1.23–1.66 <0.0001

History of renal insufficiency 1.48 1.19–1.84 0.0004

History of bleeding 2.83 1.94–4.13 <0.0001

Mean arterial pressure 1.11 1.04–1.19 0.0016

Thrombolytics only 1.43 1.14–1.78 0.0017

GP IIb/IIIa blockers only 1.93 1.59–2.35 <0.0001

Thrombolytics and GP IIb/IIIa blockers 2.38 1.69–3.35 <0.0001

PCI 1.63 1.36–1.94 <0.0001

Right heart catheterisation 2.48 1.98–3.11 <0.0001

OR = odds ratio; CI = confidence interval GP = glycoprotein; PCI = percutaneous coronary intervention

Moscussi M, et al.Eur Heart J 2003;24:1815–23

Non-CABG TIMI major bleeding: in selected subgroups of the TRITON TIMI 38 study

Prasugrel better Clopidogrel 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

History of stroke or TIA Yes

No

At least one of: age 75 years, body weight <60kg, or history stroke/TIA

Yes

No

p† value

p‡

interaction

0.06 –

0.08 0.22

0.10 –

0.17 0.64

Adapted from: Wiviott S, et al. NEJM 2007;357:2001–15

Hazard ratio (95% CI)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

Any cause death, non-fatal MI, non-fatal stroke, non-CABG TIMI major bleeding in selected subgroups of the TRITON TIMI 38 study

Prasugrel better Clopidogrel better

History of stroke or TIA Yes

No

Yes

No

0.04 –

<0.001 0.006

0.43 –

<0.001 0.006

Hazard ratio (95% CI)0.5 0.8 1.0 1.3 1.5 1.8 2.0 2.3 2.6

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 2007;357:2001–15

p† value

p‡

interaction

At least one of: age 75 years, body weight <60kg, or history stroke/TIA

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 V1–V6

Troponin: 0.5 (normal <0.004)

Normal creatinine levelBMI = body mass index; ECG = electrocardiogram

Is this patient at low, moderate or high risk for ischaemic events?

Is this patient at low, moderate or high risk for bleeding complications?

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

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

Coronary angiogram

Coronary angiogram

Bare metal stent (2.75 x 15)

Two days later . . .

Would you initiate a GP IIb/IIIa inhibitor?

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

What would you do?

IVUS

Undersized stent (2.8mm; RVD 3.5mm)

Balloon inflation (3.5 X 12 at 22 atm)

Balloon 3.5 X 12 at 22atm

Stent thrombosis

Technical issues

Undersized stentUncovered dissection

Patient selection

Heavily calcified lesionsSmall vesselsLong lesions

Platelet aggregation

New therapeutic approaches

Treatment of NSTEMI: a balancing act

Careful patient selection– age, gender, past history of

bleeding, low weight, renal insufficiency

Clinical benefit of a drug– reduces mortality

Bleeding complications– increases mortality