Transcript UA/NSTEMI Guidelines

UA/NSTEMI Guidelines
Dr. Sajeer K.T
Senior Resident
Dept. of Cardiology
Definition UA/NSTEMI
Electrocardiographic ST segment depression or
prominent T wave inversion
and/or
Positive biomarkers of necrosis (troponin )
In the absence of ST segment elevation
In an appropriate clinical setting ( chest discomfort or
anginal equivalent)
ACC/AHA Task force on practice guidelines
• 2007
• 2011 focused updates
Risk stratification
Early hospital care
Conservative management strategy
 Invasive management strategy
Risk stratification
• Diagnostic evaluation:
• Assesses the risk that a pt with UA/NSTEMI has for MI or
death during next few weeks.
•
Focuses on history
Physical findings
ECG findings
Biomarkers of cardiac injury (Cardiac specificTroponin)
TIMI score
Variables Used in the TIMI Risk Score
•Age ≥ 65 years
•At least 3 risk factors for CAD
•Prior coronary stenosis of ≥ 50%
•ST-segment deviation on ECG presentation
•At least 2 anginal events in prior 24 hours
•Use of aspirin in prior 7 days
•Elevated serum cardiac biomarkers
The TIMI risk score is determined by the sum of the presence of the above 7 variables at
admission. 1 point is given for each variable. Primary coronary stenosis of 50% or more
remained relatively insensitive to missing information and remained a significant predictor of
events.
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TIMI Risk Score
TIMI
Risk
Score
All-Cause Mortality, New or Recurrent MI, or Severe
Recurrent Ischemia Requiring Urgent Revascularization
Through 14 Days After Randomization %
0-1
4.7
2
8.3
3
13.2
4
19.9
5
26.2
6-7
40.9
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Early Hospital care
Anti ischemic therapy and analgesic therapy
class 1
– Bed rest with continuous ECG monitoring
– Supplemental oxygen ( if spo2<90% or respiratory
distress).
– sublingual nitrate every 5 min for a total of 3 doses .
– IV NTG in first 48 hrs
- persistent ischemia
- HF
- hypertension
Anti ischemic therapy contd..
class 1
- Oral beta-blocker therapy ( within the 1st 24 h)
Contraindications:
1) signs of HF
2) low out put state( SBP<90,oliguria,HR<50)
3) other relative contraindications to beta blockade.
(PR > 0.24 s, 2nd or 3rd degree AV block,
active asthma or reactive airway disease).
4) increased risk for cardiogenic shock
Risk factors for increased cardiogenic shock
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Older age
Female sex
Time delay
Higher killip class
SBP<120
HR>110 or <60
If Beta blockers are contra indicated
Nondihdropyridine calcium channel blockers
- Verapamil
- Diltiazem
Contraindications for CCBs:
Severe LV dysfunction
COMMIT Trial
•45,852 patients within 24 h acute MI
― 93% STEMI or LBBB, 7% had NSTEMI
•Up to 15 mg IV → 50 mg po metoprolol daily v/s placebo
• composite primary outcomes
― death, reinfarction, or cardiac arrest
•No decrease of com-primary outcome by metoprolol
- modest reduction in reinfarctions and VF
• Risk cardiogenic shock especially with initial hemodynamic
instability
•Recommend: start -blocker po when hemodynamically stable
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ACEI & ARBs
ACE inhibitor (orally within 1st 24 h) in patients with
- pulmonary congestion
- LVEF ≤ 40%
contraindications:
- hypotension
(SBP < 100 mm Hg or < 30mm Hg below baseline)
- known contraindications ACEIs
ARBs: if intolerance to ACEI
(class IIa)
 IV morphine
 IV beta blocker : in HTN with UA/NSTEMI
( with no CI for Beta Blocker)
 Oral long acting non-DHP CCBs :
for recurrent ischemia if no CI
( after nitrates and beta blockers)
 Oral ACEI
- in pts with out - pulmonary congestion
- LVEF≤ 40%
Intra aortic balloon counter pulsations
(IABP)
• For continuing severe ischemia
• For hemodynamic unstability
Class IIa
 Nitrates :
- SBP<90 or ≥ 30mm Hg below the baseline.
- with in 24 hr of PDEIs ( sildenafil& tadalafil)
 IV ACEI : ↑ ed risk of hypotension
 IV beta blockers : with CI to Beta blockade
 NSAIDs ( except ASA):
a/w ↑ mortality, reinfarction, HTN, HF,
myocardial rupture
Class III
Antiplatelet therapy
Antiplatelet therapy
class 1
Aspirin : as soon as possible (165-325 mg)
- (non enteric formulation orally or chewed).
-Continued indefinitely(75-162mg/d ) in pts who
tolerate it.
Clopidogrel :
- loading dose -300mg
- daily maintenance dose 75mg
- Continued for at least 1 month and ideally up to 1 year.
CURE trial
• 12,562 patients with UA/NSTEMI presenting with in 24 hrs
• Clopidogrel 300mg loading >>>75mg/d v/s placebo
• All patients received ASA
• Significant reductions in the rate of in-hospital severe ischemia
and revascularization and need for IV GPIIb/IIIa inhibitors.
• Strong evidence for addition of clopidogrel to ASA on
admission in management of patients in whom a noninterventional approach is intended.
• Useful approach in hospitals that do not have a routine policy
about early invasive procedures
Use of Proton pump inhibitors
Interfere with the metabolism of clopidogrel
- Lansoprazole
inhibits CYP450 2C19
- Rabeprazole
Omeprazole : significantly decrease the inhibitory effect of
clopidogrel on platelet aggregation.
Pantoprazole lacks inhibition of CYP450 2C19
-- Deleted recommendation
2011
Anti coagulant therapy recommendations
Class I
Invasive strategy:
- UFH
- Enoxaparin
- Bivalirudin
Conservative strategy:
- UFH or Enoxaparin
- Fondaparinux
( preferable in pts with increased risk of bleeding)
Enoxaparin or fondaparinux preferable to UFH unless CABG
is planned with in 24 hrs
Class IIa
UFH dosage
• ACC/AHA Guidelines recommend
weight-adjusted dose of UFH
: 60 units/kg bolus and
: 12 units/kg/hr infusion.
Select Management Strategy:
Initial Conservative Strategy
Versus
Initial Invasive strategy
UA/NSTEMI
Conservative strategy
Anticoagulant therapy:
Enoxaparin or UFH
Fondaparinux
Initiate clopidogrel
ASA
( Clopidogrel if
ASA intolerance)
Invasive strategy
Anticoagulant therapy:
Enoxaparin or UFH
Bivalirudin
Pre cath:
Add second antiplatelet agent:
-Clopidogrel
-GPIIb/IIIA inhibtor
(IV eptifibatide or tirofiban)
Next step per triage decision at angiography
CABG:
Maintenance ASA
PCI:
Clopidogrel (if not
begun precath)
Or
Prasugrel
Or
GPIIB/IIIA inhibitor (if
not begun precath
Medical therapy:
-D/C GPIIb/IIIainhibitor
and give clopidogrel as
per conservative
strategy
Initial Conservative management
Strategy
UA/NSTEMI
Conservative
strategy
ASA
+
Anticoagulant therapy
Clpidogrel (30-600 mg→→ 75mg)
-ASA continued indefinitely
-Clpidogrel continued for at least 1 month and ideally up to 1 year
UA/NSTEMI- conservative strategy
Class 1
No subsequent features that necessitates CAG
EF<40%
LV EF
EF>40%
Stress testing
Low risk
High Risk
CAG
-ASA indefinitely
-Clopidogrel – 1 month (ideally up to 1 year)
-Discontinue IV GPIIb/IIIa inhibitor if started
previously
-Continue UFH for 48 hrs or administer
enoxaparin or fondaparinux max up to
8days or
duration of hospitalization
ACC/AHA noninvasive risk stratfication:
high risk (>3% annual mortality rate)
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severe resting LV dysfunction (LVEF<35%)
High risk TMT score (score≤ -11)
Severe exercise LV dysfunction (LVEF<35%)
Stress induced large perfusion defect (if ant.)
Stress induced multiple perfusion defects
Large fixed perfusion defect with LV dialatation or increased
lung uptake (thallium 201)
• Stress induced moderate perfusion defect with LV dialatation
or increased lung uptake (thallium 201)
• Echo wall motion abn.at low dose dobutamine
• Stress echo evidence of extensive ischemia
UA/NSTEMI- Conservative Strategy
Class IIa
Recurrent ischemic discomfort with ASA+ Clopidogrel+Anticoagulant
treatment
Add a GPIIb/IIIa inhibitor before diagnostic CAG
Omit GPIIB/IIIa inhibitors if bivalirudin is selected as the anticoagulant
& 300-600 mg clopidogrel was administered 6 hours earlier than
planned CAG or PCI
Management after Diagnostic Angiography in Patients with
UA/NSTEMI
Dx Angiography
Select Post Angiography Management Strategy
CABG
• Cont ASA .
• DC clopidogrel 5 to 7 d prior to
PCI
• Cont ASA
• LD of clopidogrel if not given
elective CABG.
• DC IV GP IIb/IIIa 4 h prior to
CABG
• Cont UFH
•
DC enoxaparin 12 to 24 h prior to
CABG;
• DC fondaparinux 24 h prior to
CABG;
• DC bivalirudin 3 h prior to
CABG. Dose with UFH per
institutional practice
pre angio
Medical therapy
No
significant
obstructive
CAD on
angiography
&
CAD on angiography
• Cont ASA
• LD of clopidogrel if not
• IV GP IIb/IIIa if not started
given pre angio
pre angio
• DC ACT after PCI for
uncomplicated cases
Antiplatelet
and ACT at
physician’s
discretion
(Class I,
LOE: C)
• DC IV GP IIb/IIIa after
at least 12 h if started pre angio
• Cont IV UFH for at least 48 h
•
or
enoxaparin or fondaparinux for dur of
hosp ;
either DC bivalirudin or cont at a dose
of 0.25 mg/kg/hr for up to 72 h at
physician‘s discretion .
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UA/NSTEMI- CABG selected as post angiography
management
Class 1
-
-Continue ASA
-Discontinue clopidogrel - 5 days prior to CABG
-(discontinue prasugrel - 7 days prior to CABG)
-Discontinue IV GPIIb/IIIa inhibitor (eptifibatide or tirofiban)
4 hrs before CABG.
-Continue UFH
- Discontinue enoxaparin & fondaparinux 12-24 hrs bfore
CABG and dose with UFH per institutional practice
-Discontinue bivalirudin 3 hours before CABG and dose with
UFH as per institutional practice
UA/NSTEMI- PCI has been selected as post angiography
management
Class 1A
-Continue ASA
- loading dose of thienopyridines if not given before CAG –
- clopidogrel 300-600 mg
- prasugrel 60 mg
-IV GPIIa/IIIa inhibitor (abciximab, eptifibatide, tirofiban ) if not
started before CAG (in troponin-positive and /or high risk patients)
- Class IIa
-Discontinue anticoagulant therapy after PCI for uncomplicated cases
UA/NSTEMI –medical therapy is selected as management
strategy
+ obstructive CAD
-ASA
-clopidogrel
-discontinue IV GPIIb/IIIa inhibitor if started previously
Anti coagulant therapy
Continue intravenous UFH for at least 48 h or until discharge if given
before diagnostic angiography
Continue enoxaparin or fondaparinux for duration of hospitalization or
up to 8 days.
Discontinue Bivalirudin
UA/NSTEMI –medical therapy is selected as management
strategy
-No significant obstructive CAD-
Antiplatelet and anticoagulant therapy at the
discretion of physician
Luminal irregularities with out flow limiting lesions
–long term ASA
UA/NSTEMI – conservative strategy
-who do not undergo CAG or stress testing
-ASA indefinitely
-Clopidogrel for at least 1 month ( ideally up to 1 year)
-Discontinue GPIIb/IIIa inhibitor if started previously
-Continue UFH for 48 hrs
or
-Enoxaparin or fondaparinux ( 8 days or dur.hosp.)
Initial Invasive management
strategy
Relative Risk of All-Cause Mortality for Early Invasive Therapy
Compared With Conservative Therapy at a Mean Follow-Up of 2 y
Bavry AA, et al. J Am Coll Cardiol 2006;48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative risk.
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Relative Risk of Recurrent Nonfatal MI for Early Invasive
Therapy Compared With Conservative Therapy at a
Mean Follow-Up of 2 y
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. CI = confidence interval; RR = relative risk. Reprinted with permission from Elsevier.
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Relative Risk of Recurrent UA Resulting in Rehospitalisation
for Early Invasive Therapy Compared With Conservative
Therapy at a Mean Follow-Up of 13 Months
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative
risk; UA = unstable angina.
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Recommendations for initial invasive strategies
Class I
- refractory angina
- hemodynamic instability
- arrhythmias
- Elevated risk of clinical events
Initially stabilized high risk patients –reasonable to choose
early invasive strategy
(With in 12-12 hrs)
Class IIa
High risk clinical events
 Recurrent angina/ischemia at rest
with low-level activities despite
intensive medical therapy
Elevated cardiac TnT or TnI
 New/presumably new STsegment depression
Signs/symptoms of heart failure
or new/worsening mitral
regurgitation
High-risk findings from
noninvasive testing
Hemodynamic instability
Sustained ventricular tachycardia
PCI within 6 months
Prior CABG
 High risk score (e.g., TIMI,
GRACE)
- LVEF < 40%)
UA/NSTEMI
Invasive strategy
Dual –antiplatelet on presentation
Initiate anticoagulant therapy :
Enoxaparin or UFH
Bivalirudin
Before PCIclopidogrel or
IV GpIIb/IIIainhibitor-tirofiban or eptifibatide
At the time of PCIclopidogrel (if not started) or
Prasugrel
IV GpIIb/IIIa-tirofiban or eptifibatide (if not begun pre catheterization)
Recommendations in whom PCI is planned (2011)
Class 1
Clopidogrel loading 300-600 mg should be given as early as
possible before or at the time of PCI
Or
Prasugrel 60 mg should be given promptly and not later than 1
hour after PCI once coronary artery anatomy is defined.
Class III
 No Abciximab to patients in whom PCI is
not planned.
 Upstream GPIIa/IIIa inhibitors are not
recommended in
-TIMI score ≤ 2( low risk for ischemic events)
- at high risk of bleeding
Prasugrel contraindicated in
-Prior h/o TIA or stroke
Duration and maintenance of thienopyridine therapy (2011)
Class 1
Clopidogrel 75 mg daily
or
Prasugrel 10 mg daily
Duration : Up to 12 months
If the risk of morbidity because of bleeding outweighs the benefit by
thienopyridine therapy earlier discontinuation can be considered
Long term Antiplatelet therapy
Class I
Medical therapy
ASA 75-162
mg/d indefinitely
&
Clopidogrel 75
mg/d for at least
1 month and
ideally up to 1
year
BMS group
ASA 162-325 mg/d
(1 month)
↓
75-162 mg/d
(indefinitely)
&
Clopidogrel 75
mg/d or Prasugrel
10 mg/d (for at
least 1 year)
DES group
ASA 162-325 mg/d
(SES-3months)
(PES-6months)
↓
75-162 mg/d
(indefinitely)
&
Clopidogrel 75 mg/d
Or
prasugrel 10mg for
at least 1 year
2011 new recommendation
class IIb
• Continuation of clopidogrel /prasugrel beyond
15 months may be considered in patients
following DES placement
Revascularization Strategy in
UA/NSTEMI
Cardiac cath
CAD
No
Discharge from
protocol
Yes
CABG
Yes
Left main disease
No
1- or 2Vessel
Disease
Medial
Therapy, PCI
or CABG
3- or 2-vessel disease with
proximal LAD involvement
LV dysfunction or
treated diabetes*
No
PCI or CABG
Yes
CABG
*There is conflicting information about these patients.
Most consider CABG to be preferable to PCI.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157,
Figure 20.
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Lipid Management
Lipid management should include assessment of a fasting lipid
profile for all patients, within 24 h of hospitalization.
High dose statins in the absence of contraindications, regardless
of baseline LDL-C and diet modification, should be given to
post-UA/NSTEMI patients, including post revascularization
patients.
LDL goal: <100mg/dl
<70 mg/dl reasonable (classIIa)
Meta analysis of intensive v/s standard statin therapy, showing a highly
significant 16% reduction in the risk of coronary death or MI
(p<0.0001)
Lipid Management contd..
Dietary therapy :
-Reduced intake of saturated fats to < 7% of total calories
-cholesterol to < 200 mg per d
- trans fat (to < 1% of energy).
Promoting daily physical activity and weight management are
recommended
Lipid Management
If TG are ≥ 500 mg per dL:
- Fibrate or niacin
LDL-C be treated to goal after TG-lowering therapy.
High dose statin+ fibrate can increase the risk of severe
myopathy
Statin doses kept low in this combination
Blood Pressure Control
Blood pressure control according to JNC 7 guidelines is
recommended
(i.e., BP < 140/90 mm Hg or < 130/80 mm Hg if the
patient has diabetes mellitus or chronic kidney disease).
Diabetes mellitus
• Use insulin infusion to control hypeglycemia
• control blood glucose from a more stringent to
a more moderate target range .
• Recommend treatment for hyperglycemia>180
mg/dl while avoiding hypogylcemia
• NICE-SUGAR trial:
ADA RECOMMENDATION
“ Although hyperglycemia is associated with
adverse outcomes after acute MI, reduction of
glycemia per se and necessarily the use of
insulin is a/w improved outcomes”
Chronic Kidney Disease
Creatinine clearance should be estimated in UA/NSTEMI
patients.
Doses of renally cleared drugs should be adjusted according to
the pharmacokinetic data of specific medications.
Chronic Kidney Disease contd…
Patients undergoing CAG with receipt of contrast media
should receive adequate preparatory hydration.
Calculation of the contrast volume to Cr Cl ratio is useful to
predict the maximum volume of contrast media that can be
given with out significantly increasing the risk of contrast
associated nephropathy
TIME IS PRECIOUS
• Creatinine clearance( an approximation of
GFR)
• is measured from plasma and urinary
creatinine excretion rates for a defined time
period (usually 24 h)
• is expressed in milliliters per minute:
• CrCl = (Uvol x UCr)/(PCr x Tmin).
• Cockcroft-Gault:
• CrCl (mL/min) = (140 – age (years) x weight
(kg) x [0.85 if female])/(72 x sCr (mg/dL)
Fragmin during Instability in Coronary Artery
Disease (FRISC-2)
• Patients within 48 h UA/NSTEMI
• Early inv vs conserv & dalteparin vs placebo
• 3048 patients → dalteparin for 5–7 d → 2457 continued
dalteparin/placebo & received either inv or conserv rx strategy
• Meds: ASA, β-blockers unless contraindicated
• No ↓ death/MI @ 3 mo by dalteparin
• ↓ Death/MI @ 6 mo, 1 y & 5 y for inv strategy
― Benefit confined to men, nonsmokers, and patients with ≥ 2 risk
factors
Wallentin L, et al. Lancet 2000;356:9–16 (1-year results). Lagerqvist B, et al. J Am Coll Cardiol 2001;38:41–8 (women vs men).
Lagerqvist B, et al. Lancet 2006;368:998–1004 (5-yr follow-up).
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Treat Angina with Aggrastat and Determine Cost of
Therapy with an Invasive or Conservative Strategy
(TACTICS-TIMI-18)
•
•
•
•
2,220 patients within 24 h UA/NSTEMI
Early inv or conserv (selective invasive) strategy
Meds: ASA, heparin and tirofiban
↓ Death, MI, and rehosp for an ACS @ 6 mo for inv strategy
― Benefit in medium and high-risk patients (TnT ↑ of > 0.01 ng/mL,
ST-segment deviation, TIMI risk score > 3)
― No high-risk features, outcomes ↔
― ↓ Death/MI @ 6 mo for older adults with early inv strategy
― Benefit of early inv strategy for high-risk women (↑ TnT); low-risk women
tended to have worse outcomes, incl ↑ risk of major
bleeding
Cannon CP, et al. N Engl J Med 2001;344:1879–87.
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Third Randomized
Intervention Treatment of Angina (RITA-3)
• 1,810 moderate-risk ACS patients
• Early inv or conserv (ischemia-driven) strategy
• Exclusions: CK-MB > 2X ULN @ randomization, new Q-waves, MI
w/in 1 mo, PCI w/in 1 y, any prior CABG
• ↓ Death, MI, & refractory angina for inv strategy
― Benefit driven primarily by ↓ in refractory angina
• ↓ Death/MI @ 5 y for early inv arm
• No benefit of early inv strategy in women
Fox KA, et al. Lancet 2002;360:743–51. Fox KA, et al. Lancet 2005;366:914–20 (5-y results).
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Clopidogrel in Unstable angina to prevent
Recurrent ischemic Events (CURE)
•12,562 patients within 24 h UA/NSTEMI
•Placebo vs clopidogrel (LD 300 mg → 75 mg qd)
•Other meds: ASA
•↓ CV death, MI, or stroke, rate of recurrent ischemia & revasc with
clopidogrel
•↑ Major (non–life-threatening) bleeding with clopidogrel
•No routine inv strategy, 23% revasc during initial admission
•Although well tolerated, < 10% GP IIb/IIIa + ASA + clopidogrel +
heparin use in study patients
Yusuf S, et al. N Engl J Med 2001;345:494–502.
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Platelet Receptor Inhibition in Ischemic Syndrome
Management
in Patients Limited by Unstable Signs and Symptoms (PRISMPLUS)
•1,915 patients within 12 h UA/NSTEMI
•Tirofiban alone, UFH alone, or both for 48–108 h.
•Tirofiban-alone arm discontinued d/t ↑ mortality rate.
•↓ Death, MI, or refractory ischemia at 7 d, 30 d & 6 mo by tirofiban
+ heparin
•High rate of angio could have contributed to important ↓ in event
rates
•Recommend: Tirofiban + heparin for medical rx or during PCI
PRISM-PLUS Study Investigators. N Engl J Med 1998;338:1488–97.
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Relative Risk of All-Cause Mortality for Early
Invasive Therapy Compared With Conservative
Therapy at a Mean Follow-Up of 2 y
Bavry AA, et al. J Am Coll Cardiol 2006;48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative risk.
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Relative Risk of Recurrent Nonfatal MI for Early Invasive
Therapy Compared With Conservative Therapy at a
Mean Follow-Up of 2 y
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. CI = confidence interval; RR = relative risk. Reprinted with permission from Elsevier.
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Relative Risk of Recurrent UA Resulting in Rehospitalisation
for Early Invasive Therapy Compared With Conservative
Therapy at a Mean Follow-Up of 13 Months
Bavry AA, et al. J Am Coll Cardiol 2006; 48:1319–1325. Reprinted with permission from Elsevier. CI = confidence interval; RR = relative
risk; UA = unstable angina.
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SYMPTOMS SUGGESTIVE OF
ACS
Noncardiac
Diagnosis
Chronic Stable
Angina
Definite ACS
Possible
ACS
No ST-Elevation
Treatment as
indicated by
alternative diagnosis
ACC/AHA Chronic
Stable Angina
Guidelines
Nondiagnostic ECG
Normal initial serum
cardiac biomarkers
Observe
ST and/or T wave changes
Ongoing pain
Positive cardiac
biomarkers
Hemodynamic
abnormalities
≥ 12 h from symptom onset
No recurrent pain; negative
follow-up studies
Recurrent ischemic pain or
positive follow-up studies
Stress study to provoke ischemia
Diagnosis of ACS
confirmed
Consider evaluation of LV function if
ischemia is present (tests may be
performed either prior to discharge or as
outpatient)
Evaluate for
reperfusion
therapy
ACC/AHA STEMI
Guidelines
Negative
Positive
Admit to hospital
Potential diagnoses:
nonischemic discomfort; lowrisk ACS
Diagnosis of ACS
confirmed or highly likely
Manage via acute ischemia pathway
Arrangements for outpatient follow-up
ST-Elevation
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