Challenging cases and risk assessment in clinical practice Christian Spaulding MD, PhD, FESC, FACC Cardiology Department Cochin Hospital Paris Descartes University Paris, France
Jun 02, 2015
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