nstemi acute coronary syndromes patrick hildbrand
TRANSCRIPT
Trends and Prognosis in NSTEMI
Furman MI, JACC 2001, 37:1571-1580Hospital 1 year
Trends and Prognosis
Diagnosis and Risk assessment
Initial ManagementTreatment <
Long-Term Management
Summary of Treatment Approaches
NSTEMI Acute Coronary Syndromes
Chest Pain
ECG
Kaul P, JACC 2001, 38:64-71
Biochemistry
Risk Stratification
Summary Diagnosis and Risk assessment
Diagnosis and short-term risk stratification should be based on a combination of
Clinical history Symptoms ECG and (10 minutes, 6h, 24h and before hospital discharge) Biomarkers (admission and after 6-12 h) Risk score results
Echocardiography is recommended to rule out differential diagnosis
Patient without recurrence of pain, normal ECG findings and negative troponins tests > non invasive stress testing
Trends and Prognosis
Diagnosis and Risk assessment
Initial ManagementTreatment <
Long-Term Management
Summary of Treatment Approaches
NSTEMI Acute Coronary Syndromes
Therapeutic Options
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors
Revascularization
NSTEMI
Anti-Ischemic Agents
Aim: Decrease myocardial oxygen consumption and/or induce vasodilatation
Betablockers are recommended in absence of contraindications (hypertension and tachycardia; cave inferior MI, acute LV
dysfunction) (IB)
Nitrates are effective in symptom relief in the acute management of angina episodes (IC)
(Cave: Phospodiesterase-5-inhibitors, RV MI)
Calcium channel blockers provide symptom relief in patients already receiving betablockers and nitrates; patient with contraindication to betablockers; vasospastic angina (Ic)
Nifedipine or other dihydropyridine should not be used (IIIC) unless combined with betalockers (IIa-B)
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agentsASAClopidrogelGP IIb/IIIa Inhibitors
Revascularization
NSTEMI
UFH
LMWH
UFH33% RR
Enoxaparin (©Clexane) vs UFH
NON REVASC.
GP IIb/IIIa Inhibitors
GP IIb/IIIa Inhibitors
Enoxaparin was non-inferior to UFH in Reducing death or MI in the Synergy Trial
Synergy 14% versus 14.5% p=n.s.
Factor-Xa inhibitors (Fondaparinux, © Arixtra)
Oasis 5 TrialDeath, MI or refractory ischemia through day 9
Oasisi 5: Major bleeding through d9
Relation between bleeding and mortality in OASIS 5
Bleeding carries a high risk of death
Prevention of bleeding is as important as prevention of ischemic events and results in a significant rate reduction of death
> Risk stratification of bleeding should be part of the decision making process
Direct thrombin inhibitors (Bivalirudin, ©Angiox) UFH/LMWH
Acuity Trial
Primary Endpoint Measures Net clinical outcome
Cave: hematoma > 5cm never used in any other definition
Summary Anti-coagulants
Anticoagulation is recommended for all Patient in addition to anti-platelet therapy
Anticoagulation should be selected to the risk of both ischemic and bleeding events
Choice of the anticoagulants (UFH, LMWH, fondaparinux and bivalirudin should depend on the strategy.
Urgent invasiv
UFH (I-C), Enoxaparin (IIa-B) or bivalirudin (I-B)
Non-urgent situation
Fondaparinux efficacy/safety profile (I-A)
Enoxaparin only if bleeding risk is low (IIa-B)
>> not LMWH (other then Enoxaparin) / UFH
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors
Revascularization
NSTEMI
Anti-platelet agents
ASA
GI intolerance 5-40%, bleeding >0.9% in CAPRIE
Primary End Point—MI/Stroke/CV Death
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Cum
ulat
ive
Haz
ard
Rat
e
Clopidogrel + ASA*
3 6 9
Placebo + ASA*
Months of Follow-Up
P = 0.00009†
N = 12,562
0 12
20%Relative Risk
Reduction
CURE Study
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
PCI-CURE Study: CV Death or MI
.00
.05
.10
.15
0 10 100 300 400200
Cu
mu
lati
ve H
aza
rd R
ate
Clopidogrel + Aspirin*(n=1313)
31% RelativeRisk Reduction
Placebo + Aspirin*(n=1345)Median
time to PCI
Days of Follow-Up
12.6%
8.8%
P=0.002
*In combination with standard therapy.Mehta SR, et al. Lancet. 2001;358:527-533.
GP IIb/IIIa Inhibitors
Tirofiban
Eptifibatide
Abciximab
Lamifibane
Lamifibane
Acuity timing
Summary GP IIb/IIIa Inhibitors
Intermediate to high risk (DM, ST segment depression and Troponin pos.) patients, either eptifibatide or tirofibane for initial early treatment is recommended in addition to oral antiplatelet agents (IIa-A)
Patient not pre-treated with GP IIb/IIIa inhibitors and proceeding to PCI; abciximab is recommended (IA)
GpIIb/IIIa inhibitors must be combined with anticoagulation I-A
Bivaluridin may be used as an alternative to GPIIb/IIIa inhibitors plus UFH/LMWH (IIa-B)
GPIIb/IIIa inhibitors only for invasive strategy
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors
Revascularization
NSTEMI
Coronary revascularization
Randomized trials comparing early invasive (dark bars)
vs. conservative strategy (open bars)
Summary Invasive vs. Conservative Strategies
New data coming from long-term follow up of RITA-3 and FRISC-2 and Mehta meta-analysis show significant risk reduction for death
and „death & MI“ at long-term follow up
Early hazard shown in ICTUS Trial
Early hazard shown in Mehta meta-analysis
ICTUS, Lancet 2007FRISC 2, Lancet 2000
RITA 3 Lancet 2005Metha JAMA 2005
Summary Therapeutic Options
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors
Revascularization
NSTEMI
Trends and Prognosis
Diagnosis and Risk assessment
Initial ManagementTreatment <
Long-Term Management
Summary of Treatment Approaches
NSTEMI Acute Coronary Syndromes
ATC 2002: Indirect Comparisons ASA Doses on Vascular Events in High Risk Patients
0 0.5 1.0 1.5 2.0
500-1500 mg 34 19%
160-325 mg 19 26%
75-150 mg 12 32%
<75 mg 3 13%
Overall 65 23%
Antiplatelet Better
Antiplatelet Worse
ASA Dose # Trials OR
Antithrombotic Trialists’ Collaboration BMJ 2002; 324:71-86
Primary End Point—MI/Stroke/CV Death
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Cum
ulat
ive
Haz
ard
Rat
e
Clopidogrel + ASA*
3 6 9
Placebo + ASA*
Months of Follow-Up
P = 0.00009†
N = 12,562
0 12
20%Relative Risk
Reduction
CURE Study
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
ACE-Inhibitors
HOPEHOPE
HOPE: N Engl J Med. 2000;342:145-153.
P<.001RRR=22%
0
5
10
15
20
0 500 1000 1500
Follow-Up (days)Pat
ien
ts R
each
ing
Co
mp
osi
te E
nd
Po
int
[MI,
Str
oke
, CV
Dea
th]
(%)
Ramipril
Placebo
CV
Dea
th, M
I, o
r C
ard
iac
Arr
est
(%)
Placebo annual event rate: 2.4%
Perindopril
Placebo
P=.0003RRR=20%
Years
0 1 2 3 4 5
N = 12,218
14
12
10
8
6
4
2
EUROPA:. Lancet. 2003;362:782-788.
PEACE:N Engl J Med. 2004;351:2058-2068. 0 1 2 3 4 5 6
30
25
20
15
10
5
0
Placebo
Trandolapril
Inci
den
ce o
f P
rim
ary
En
d P
oin
t (%
)
Years After Randomization
EUROPA
PEACE
Disease Modifying Drugs in Atherothrombosis
Statins
Prevent CV events
Prevent progression of CAD
Prevents development of DM
ACE-Inhibitors/ARB’s
Prevent CV events
Prevent renal dysfunction in DM
Clopidogrel
Prevents CV events
Non-ST-segment Elevation Acute Coronary Syndromes
Anti-ischemic agents
Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin)
Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors
Revascularization
NSTEMI
?
Timing of Intervention Few studies have shown superiority of very early intervention vs. deferred intervention
ISAR-COOL (small sample size) JAMA 2003
Many trials have shown early hazard with early intervention vs. deferred intervention
ICTUS trial NEJM 2005
Mehta meta-analysis JAMA 2005
Grace and Crusade registries Heart 2007, Arch Intern Med 2006
> Timing of intervention recommended on the basis of risk stratification
Risk Stratification
Summary Management Strategy
Summary Long-Term Management
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