Download Therapy of Acute Coronary SyndromeTherapy of Acute Coronary

Treatment of acute coronary
syndrome
MUDr. Denisa Jahnlová
Department of Cardiology
FN Motol and 2nd Medical Faculty of the Charles University
Acute coronary syndromes
• Pathophysiologic mechanism
– vulnerabile plaque disruption with superimposed thrombus and subsequent coronary blood
flow cessation with reduced myocardial supply → acute ischemia → necrosis
• Leading symptom - chest pain
• 2 groups according to ECG
• Patients with acute chest pain and persistent (20 min) ST-segment elevation
– This condition is termed ST-elevation ACS and generally reflects an acute total coronary
occlusion
– Most patients will ultimately develop an ST-elevation myocardial infarction (STEMI)
– Immediate reperfusion by primary angioplasty or fibrinolytic therapy
• Patients with acute chest pain but no persistent ST-segment elevation
– ECG changes may include transient ST-segment elevation, persistent or transient STsegment depression, T-wave inversion, flat T waves or pseudo-normalization of T waves or
the ECG may be normal
– NSTEMI - myocardial necrosis
– NAP - myocardial ischemia without cell loss, lower risk of death
Epidemiology
• Incidence of NSTEMI higher than incidence of STEMI
In-hospital mortality
-
Higher in STEMI patients vs. NSTEMI (7 vs. 5%)
STEMI - mortality 25-30% (1960s) → 10% (nowadays)
6 month mortality
-
Similar in both groups (12 vs. 13%)
Long-term follow-up
- Higher in NSTEMI patients
-
Older patients
Comorbidities (diabetes mellitus, renal insuficiency)
Generalized atherosclerosis including multivessel coronary disease
• Sex differences
– men account for more than 90% of patients with AMI at the age under 40y (a hormonal
profile of woman has a protective effect)
• Age differences
– in patients aged under 40 years only one coronary artery is affected
ACS with ST-segment elevation
Pre-hospital management
• Relief of Breathlessness
– O2 only to breathless, hypoxic (SaO2<95%), heart failure patient
• Relief of pain
– human reasons, sympathetic activation-vasoconstiction, increases workload of the heart
– titrated i.v. opioids (Morphine, Fentanyl) + antiemetics
• Relief of anxiety
• explain the situation to the patient, tranquillizer
• BB
– hypertensive and tachycardic patient
– metoprolol, bisoprolol, esmolol
– CAVE contraindication: acute cardiac failure, bradycardia
ACS with ST-segment elevation
Pre-hospital management
• Nitrate
– pain, hypertesion, heart failure
– sublingual, intravenous (isosorbide dinitrate 1-5 mg
i.v. in hypertensive patients)
– CAVE! Contraindications: hypotense, sildenafil →
resistent hypotension
• Monitoring vital function and ECG
– Cardiac arrest due to ventricular fibrillation!!!
• Terminated by defibrillation
• Theapeutic hypothermia after resuscitation is
indicated
• Immediate angiography in patients with CA
whose ECG shows STEMI/high suspicion on
ongoing infarction
ACS with ST-segment elevation
Reperfusion therapy: time is muscle!!!
• Indication
– within 12 h of symptom onset with persistent STE or new LBBB (later → necrosis)
– in patients with ongoing ischemia → later
– within 120 minutes of first contact with doctor
• Types of RT
– mechanical (PCI)
• preferred reperfusion strategy
• randomized clinical trials → superior to fibrinolysis
– pharmacological (fibrinolysis)
Prehospital and in-hospital management
Reperfusion Strategy in Europe
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
7
1
14
0
12
7
17
2
13
12
20
10
15
25
26
15
26
36
15
5
3
21
30
39
40
31
8
35
44
37
42
48
52
50
50
10
63
40
15
35
15
92
55
35
28
86
81
81
30
26
75
75
72
70
66
64
44
33
25
59
41
49
45
35
33
30
30
28
24
23
19
19
9
CZ
SLO
DE
CH
NO
DK
PL
HR
P-PCI
SE
HU
BE
IL
IT
FIN
Thrombolysis
AT
FR
SK
ES
LAT
UK
BG
No reperfusion
Reperfusion therapy 37-93%
pPCI rate varies between 5 and 92%; Thrombolysis 0-55%
EUROPE IS VERY HETEROGENOUS!!!
45
29
45
PO
SRB GR
8
5
TR
RO
Annual Incidence of Primary PCIs
≥600 p-PCI / million / year
400-599 p-PCI / million / year
200-399 p-PCI / million / year
<200 p-PCI / million / year
Data not known
The distribution of the 22 interventional centers
working (24/7) in the Czech Republic
Population of the Czech Republic is 10 million people
ACS with ST-segment elevation
Mechanical reperfusion therapy - PCI
• Primary PCI (pPCI) is reccomended over fibrinolysis within 120 minutes of
FMC
• In unstable patients (acute heart failure/cadiogenic shock) unless related
delay
• Stenting (new generation of DES) + tromboaspiration is recommended
balloon angiopasty alone
• Radial access should be prefered over femoral access
– reduces incidence of acute bleeding events (RIVAL trial)
• pPCI should be limited to the culprit vessel
– except of patients in cardiogenic shock and persistent ischemia after PCI
Process of the implantation of stent
Aspiration trombectomy
ACS with ST-segment elevation
In-hospital care – periprocedural pharmacotheraphy
• DAPT -combination of aspirin + ATP inhibitors
– Aspirin
• For all patients without contraindications
• Initial oral loading dose 150-300 mg, 75-100 mg daily
– ATP inhibitors
• In addition to Aspirin for 12 months unless contraindications
• 3-6 months afted DES implantation in case of high bleeding risk
• Ticagrelor
– 180 mg loading dose, 90 mg twice daily in all patients with high or intermmidiate ischemic risk
• Prasugrel
– 60 mg loaging dose, 10 mg daily dose
– contraindicated in patients with prior stroke and older > 75y. and body weight <60 kg
• Clopidogrel
– 300-600 mg loaging dose,75 mg daly dose
– Only in patients who cannot recieve ticagrelor or prasugrel or who require oral antikoagulation
• PPI inhibitors in patients in risk of gastrointestinal bleeding
ACS with ST-segment elevation
In-hospital care – periprocedural
pharmacotheraphy
• Unfractionated heparin (UFH)
– in patients undergoing PCI
– 70-100 IU/Kg i.v. (max.5000 IU bolus before PCI)
– APTT 1,5-2,5x
• LMWH (low molecular weight heparin)
– 0,5 mg/kg i.v. followed by 1 mg/kg s.c.
• Fondaparinux is not recommended!
• Glykoprotein IIb/IIIa inhibitors
– Bailout therapy - only in no-reflow, massive trombus,
trombotic complications
– Only periprocedural!!!
ACS with ST-segment elevation
Pharmacological reperfusion therapy:
Fibrinolysis
• Fibrinolysis is an important in those settings where primary PCI cannot be
offered to STEMI patients within the recommended timelines
– Higher risk of bleeding, sucesfull only in 70-80%
• Within 12 h of symptom onset if primary PCI cannot be performed within
120 min
• Prehospital start
– A fibrin-specific agent (tenecteplase, alteplase, reteplase) is recommended
– Anticoagulation (UFH/enoxaparin) is recommended until revascularization and for the
duration of hospital stay
– DAPT (aspirin + clopidogrel)
• Transfer to a PCI-capable centre is indicated for all patients following
fibrinolysis
– Unstable patients - rescue/emergency PCI
– Stable patients – PCI in 3-24 hod
Fibrinolysis x PCI
Meta-analysis of 23 trials (n=7739 pts.)
Keeley EC. Lancet 2003
ACS with ST-segment elevation
Management during hospitalization
• The Coronary Care Unit
– Management of arrhythmias, heart failure, mechanical circulatory support and complex
(non)invasive and haemodynamic monitoring
– Patients should stay on coronary care unit for 2-3 days (at least 24 hours)
• Standard cardiology department
– Even after leaving the CCU patients are able to move around the room and in the
following days rehabilitate and before discharge they are able to walk up the stairs
• The total length of hospitalization is around 1 week
• Return to job possible approximately one month after the onset of the
symptoms
ACS with ST-segment elevation
Management at discharge
• Low-risk patients with successful pPCI could safely be discharged
from hospital at day 3
–
–
–
–
–
age <70 years
LVEF > 45%
1 or 2 VD
successful PCI
no persistent arrhythmias
ACS with ST-segment elevation
Long-term therapies
• CAD is a chronic condition and patients who have recovered
from a STEMI are at high risk for new events and premature
death !!!
• Most patients with STEMI who die do so after discharge from
the index event!
ACS with ST-segment elevation
Long-term therapies- lifestyle interventions and
risk factor control
-
cessation of smoking
tight blood pressure control
diet and weight control
the encouragement of physical activity
ACS with ST-segment elevation
Long-term therapies- pharmacotherapy
-
Antithrombotic therapy
-
-
Beta-blockers
-
-
In all patients without contraindications, especially in patients with heart failure and systolic
dysfunction
Metoprolol up to 200 mg daily, Carvediol up to 25 mg daily, Bisoprolol up to 10 mg daily
Contraindication: in patients in acute phase and heart failure, cardiogenic shock,
bradycardia
Statins
-
-
DAPT (combination of aspirin + ADP-receptor blocker) for up to 12 months
Aspirin indefinitely (75-100mg)
Tigagrelor/prasugrel is reccomended over clopidogrel for 12 months
Lipid-lowering therapy
Atorvastatin 40-80 daily, Rosuvastatin 20-40 mg daily
ACE inhibitors
-
In all patients without contraindications, especially in heart failure, left ventricular systolic
dysfunction, diabetes mellitus
Ramipril 1,25 mg, Lisinopril 2,5 mg, Enalapril 2,5 mg
In case of intolerance : Valsartan 20 mg twice daily, Losartan, Candesartan is an alternative
ACS without ST-segment elevation
• Patients with acute chest pain but no persistent ST-segment elevation
• ECG changes may include
–
–
–
–
–
–
transient ST-segment elevation
persistent or transient ST-segment depression
T-wave inversion
flat T waves
pseudo-normalization of T waves
ECG may be normal
• The clinical spectrum of non-ST-elevation ACS (NSTE-ACS) may range from
patients
–
–
–
–
free of symptoms at presentation
individuals with ongoing ischaemia
electrical or haemodynamic instability
cardiac arrest
• The pathological correlate at the myocardial level is
– NSTE-myocardial infarction (NSTEMI)- positive hsTnI, cardiomyocyte necrosis
– unstable angina –myocardial ischaemia without cell loss, negative hsTnI
ACS without ST-segment elevation
Ongoing ischemia
• Patients may present with ongoing myocardial ischaemia, characterized by
one or more of the following:
–
–
–
–
recurrent or ongoing chest pain
marked ST depression on 12-lead ECG
heart failure
haemodynamic or electrical instability
• Immediate PCI is indicated
– due to the amount of myocardium in danger and the risk of malignant
ventricular arrhythmias
ACS without ST-segment elevation- Risk score and bleeding
risk assesment
Grace risk score
Crusade bleeding risk
Estimenate the in-hospital mortality,
mortality at 6 months, at 1 year and at
3 years
The combined risk of death or MI at 1 year
Estimate the patient’s likelihood
of an in-hospital major bleeding
event
baseline patient characteristics
Variables :
age
Systolic blood pressure
pulse rate
serum creatinine
Killip class at presentation
cardiac arrest at admission
elevated cardiac biomarkers and ST deviation
female gender
history of diabetes
history of peripheral vascular disease
or stroke
admission clinical variables
heart rate
systolic blood pressure
signs of heart failure
admission laboratory values
haematocrit
calculated creatinine clearance
ACS without ST-segment elevation
Pharmacological treatment of ischaemia
•
Decrease myocardial oxygen demand or increase myocardial oxygen supply
•
O2
– only in patients with saturtion less than 90%/in respiratory distress
•
Beta-blockers
– in patients with ongoing ischaemic symptoms and without contraindications
•
Nitrates
– i.v. or sublingual
– to relieve angina, uncontrolled hypertension or signs of heart failure
– CAVE! Avoid in patients with recent intake of sildenafil
•
Opiates
– only in patients with symtoms despite the theraphy with BB and Nitrates
•
If the patient is not free of signs and symptoms after this treament, immediate
PCI is recommended!!!
ACS without ST-segment elevation
Platelet inhibition
• DAPT -combination of aspirin + ATP inhibitors
– Aspirin
• For all patients without contraindications
• Initial oral loading dose 150-300 mg, 75-100 mg daily
– ATP inhibitors
• In addition to Aspirin for 12 months unless contraindications
• 3-6 months afted DES implantation in case of high bleeding risk
• Ticagrelor
– 180 mg loading dose, 90 mg twice daily in all patients with high or intermmidiate ischemic risk
• Prasugrel
– 60 mg loaging dose, 10 mg daily dose
– contraindicated in patients with prior stroke and older > 75y. and body weight <60 kg
• Clopidogrel
– 300-600 mg loaging dose,75 mg daly dose
– Only in patients who cannot recieve ticagrelor or prasugrel or who require oral antikoagulation
• PPI inhibitors in patients in risk of gastrointestinal bleeding
ACS without ST-segment elevation
Anticoagulation
• Unfractionated heparin (UFH)
– in patients undergoing PCI
– 70-100 IU/kg i.v. (max. 5000 IU bolus berore PCI), APTT
1,5-2,5x
• Fondaparinux
–
–
–
–
–
The most favourable efficacy – safety profile in NSTEMI
Inhibition of Xa
2.5 mg s.c. daily (CAVE renal insufficiency)
OASIS-5 study – less bleeding events
Bolus UFH 70-85 IU/kg during the procedure (to avoid
formation of trombus on cathether)
• Low molecular weight heparin (LMWH)
– In patients pretreated with LMWH
– 1 mg/kg twice daly (CAVE renal insufficiency)
• Continuation
– after sucesfull PCI for 24 h
– in conservative treatment during hospital stay
ACS without ST-segment elevation
Reperfusion strategy
• PCI + implantation of stent (2nd generation DES) is the method of
choise
– Timing of PCI according to the risk stratification
• Fibrinolysis is not reccomended at NSTEMI
• CABG (surgical revascularization)
– More frequently multivessel disease with no culprit lesion
– Diabetic patients
– Higher proportion of surgical high risk charakteristics (x elective CABG)
•
•
•
•
Older age
Female gender
Left main coronary disease
LV dysfunction
– Higher bleeding and ischemic risk (timing of surgery x DAPT)
ACS without
ST-segment
elevation
Timing of
reperfusion
strategy
ACS without ST-segment elevation
Long-term therapies- pharmacotherapy
-
Antithrombotic therapy
-
-
Beta-blockers
-
-
In patients wih heart failure and systolic dysfunction
Metoprolol up to 200 mg daily, carvediol up to 25 mg daily, bisoprolol up to 10 mg daily
Contraindication: in patients in acute phase and heart failure
Statins
-
-
DAPT (combination of aspirin + ADP-receptor blocker) for up to 12 months
Aspirin indefinitely (75-100mg)
Tigagrelor/prasugrel is reccomended over clopidogrel for 12 months
Lipid-lowering therapy
Atorvastatin 40-80 daily, Rosuvastatin 20-40 mg daily
ACE inhibitors
-
Heart failure, left ventricular systolic dysfunction, diabetes mellitus
Ramipril 1,25 mg, Lisinopril 2,5 mg, Enalapril 2,5 mg,
Valsartan 20 mg twice daily, Losartan, Candesartan is an alternative when intolerance of
ACEi is present