Transcript BRAIN STEM SYNDROMES

STEMI
MANAGEMENT
• Definition
Criteria.. e/o myocardial necrosis in a clinical setting consistent with
myocardial ischaemia.
 Detection of rise &/or fall of cardiac biomarkers (preferably troponin) with
at least one value >99th percentile of the URL together with e/o
myocardial ischaemia with at least one of the following:
• Symptoms of ischaemia;
• ECG changes indicative of new ischaemia(new STE or new LBBB)
• Dvpt of pathological Q waves in the ECG;
• Imaging e/o new loss of viable myocardium or new RWMA
• For PCI/ CABG with normal baseline troponin values, elevations >99th
percentile URL are s/o peri-procedural myocardial necrosis. By convention,
increases of biomarkers >3 x 99th percentile URL have been designated as
defining PCI-related MI.
•Increases of biomarkers >5 x 99th percentile URL plus either new
pathological Q waves or new LBBB, or angiographically documented new
graft or native coronary artery occlusion, or imaging evidence of new loss
of viable myocardium ……….CABG-related MI.
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 Pathological findings of an acute myocardial infarction.
Ischemic Discomfort
Acute Coronary Syndrome
No ST Elevation
Chronology of the interface
between the patient and the
clinician through the progression of
plaque formation and the onset of
complications of STEMI.
ST Elevation
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• Prehospital Chest Pain Evaluation and Treatment
I IIa IIb III
• Prehospital EMS providers …162 to 325 mg of aspirin
(chewed) to chest pain patients suspected of having
STEMI unless contraindicated or already taken by the
patient…non–enteric-coated formulations.
• Previously on NTG take I tab S/L  Not improving after 5
mts  Seek medical help
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Prehospital Issues
Prehospital 12-lead ECG by ACLS….Class IIa (B)
Prehospital fibrinolysis….Class IIa (B)
Prehospital destination protocols
• Patients with STEMI who have cardiogenic shock and are <75 yrs old should
be brought immediately or secondarily transferred to facilities capable of
cardiac catheterization and rapid revascularization within 18 hrs of shock
(Class I)
• Patients with STEMI who have contraindications to fibrinolytic therapy
should be brought immediately or secondarily transferred promptly
(primary-receiving hospital door-to-departure time less than 30 min.) to
facilities capable of cardiac catheterization and rapid revascularization
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Fibrinolysis
Not
PCI Capable
Noninvasive Risk
Stratification
Rescue
Ischemia
driven
PCI Capable
Late
Hospital Care
and Secondary
Prevention
PCI or CABG
Primary PCI
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Initial Recognition and Management in the Emergency
Department
Examine
• 1. Airway, Breathing, Circulation (ABC)
•
2. Vital signs, general observation
•
3. Presence or absence of jugular venous distension
•
4. Pulmonary auscultation for rales
•
5. Cardiac auscultation for murmurs and gallops
•
6. Presence or absence of stroke
•
7. Presence or absence of pulses
•
8. Presence or absence of systemic hypoperfusion (cool, clammy, pale,
ashen)
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• Laboratory examinations
should be performed as part of the
management of STEMI patients, but should not delay the implementation
of reperfusion therapy.
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Serum biomarkers for cardiac damage
Complete blood count (CBC) with platelets
International normalized ratio (INR)
Activated partial thromboplastin time (aPTT)
Electrolytes and magnesium
Blood urea nitrogen (BUN)
Creatinine
Glucose
Complete Lipid Profile
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Supplemental oxygen should be administered to patients with arterial oxygen
desaturation (SaO2 < 90%)…Class I (B)
• It is reasonable to administer supplemental oxygen to all patients with
uncomplicated STEMI during the first 6 hours…Class II a
NTG : Patients with ongoing ischemic discomfort should receive sublingual
NTG (0.4 mg) every 5 minutes for a total of 3 doses, after which an
assessment should be made about the need for intravenous NTG. Class I (C)
IV NTG is indicated for relief of ongoing ischemic discomfort that responds to
nitrate therapy, control of hypertension, or management of pulmonary
congestion. Class I
Class III
• systolic pressure < 90 mm Hg or ≥ to 30 mm Hg below baseline
• severe bradycardia (< 50 bpm)
• tachycardia (> 100 bpm) or
• suspected RV infarction.
• who have received a phosphodiesterase inhibitor for erectile dysfunction
within the last 24 hours (48 hours for tadalafil).
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• Analgesia
• Morphine sulfate (2 to 4 mg intravenously with increments of 2 to 8 mg
intravenously repeated at 5 to 15 minute intervals) is the analgesic of
choice for management of pain associated with STEMI. [Class I]
• NSAIDS should be discontinued immediately at the time of STEMI ..d/t
Increased risk of cardiovascular events [A substudy analysis from the
ExTRACT TIMI-25 trial ….increased risk of death, reinfarction, heart
failure, or shock among patients on NSAIDs within 7 days of enrollment].
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• Aspirin
I IIa IIb III
• Aspirin should be chewed by patients who have not taken
aspirin before presentation with STEMI. The initial dose should
be 162 mg (Level of Evidence: A) to 325 mg (Level of Evidence: C)..
maintenance dose of 75 to 162 mg) should be given indefinitely after STEMI
to all patients without a true aspirin allergy.
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• Thienopyridines
I IIa IIb III
In patients for whom PCI is planned, clopidogrel should be started
and continued:
• ≥ 1 month after bare-metal stent
•
≥ 3 months after sirolimus-eluting stent
•
≥ 6 months after paclitaxel-eluting stent
•
Up to 12 months in absence of high risk for bleeding.
I IIa IIb III
• CABG planned ?... the drug should be withheld for at least 5 days, and
preferably for 7 days, unless the urgency for revascularization outweighs
the risk of excessive bleeding.
I IIa IIb III
• Probably indicated in patients receiving fibrinolytic therapy who are
unable to take aspirin because of hypersensitivity or GI intolerance.
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• Beta Blockers
• Oral β blockers should be given promptly to those pts without a C/I,
irrespective of concomitant fibrinolytic therapy or PCI..Class 1 (A)
• It is reasonable to administer IV β -blockers promptly to STEMI patients
without C/I, esp if a tachyarrhythmia or SHT is present Class IIa (B) ….
[COMMIT/CCS-2……. end points were not significantly reduced by
metoprolol. For every 1000 pts treated…5 fewer episodes of reinfarction &
VF, but 11 more episodes of cardiogenic shock. The excess of CS was seen
chiefly from Days 0 to 1 after hospitalization, whereas the reductions in
reinfarction and VF appeared from Day 2 onward ..
• avg relative increase in CS..30%, with higher rates for those >70 yrs, or SBP
<120 mm Hg, or presenting HR >110 bpm, or with Killip class >1.
• Pts with sinus tachycardia or AF should have LV function rapidly evaluated
before IV BBs. From Day 2 onward, when beneficial effects on reinfarction
and VF are seen, administration of 200 CR oral metoprolol daily appears to
be safe in stable patients. It is prudent to initiate with 50 mg orally every 6
hours, transitioning to a dose equivalent to 200 mg /d orally or the 13
maximum tolerated dose.]
• Glycoprotein IIb/IIIa Inhibitors
I IIa IIb III
• It is reasonable to start abciximab as early as possible before
primary PCI (with or without stenting) in patients with STEMI.
• Tirofiban or eptifibatide may be considered before primary PCI I IIa IIb III
(with or without stenting) in patients with STEMI.
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Reperfusion
• Most imp… minimize total ischemic time [time from onset of symptoms to
initiation of reperfusion therapy]….[timely use of some reperfusion therapy
is likely more important than the choice of therapy].
• TIME IS MYOCARDIUM…time - dependent “ wave - front ” of myocardial
necrosis beginning at the subendocardium and moving towards the
epicardial surface.
• goal ..rapid Rx… keep total ischemic time within 120 minutes (ideally
within 60 minutes) … door-to- needle within 30 mts or that door-toballoon within 90 mts.
• Fibrinolytics VS PCI
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• Fibrinolytics…plasminogen activators,
• directly or indirectly converts the proenzyme
plasminogen to plasmin [cleaving the arginine
560 - valine 561 bond].
• Plasmin degrades several proteins, including
fibrin, fibrinogen, prothrombin, and factors V
and VII.
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• tPA…recomb DNA tech .. five domains: finger, epidermal growth factor,
kringle 1 and kringle 2, and serum protease[resp for enzymatic activity]
.. inhibited by circulating PAI - I, so rapidly cleared (half - life about 5
minutes). So needs bolus/infusion regimens (over 1 – 3 hours).. The
accelerated dose regimen over 90 minutes produces more rapid
thrombolysis than the standard 3-hour infusion of t-PA.
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rPA…non - glycosylated, single chain deletion variant consisting only of the
kringle 2 and proteinase (plasmin cleavage site) domains of human tPA.
TNK – tPA…mutant of t-PA with specific amino acid substitutions in the kringle
1 domain and protease domain ...decrease plasma clearance, increase fibrin
specificity, and reduce sensitivity to PAI-1.
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Effects on coronary arterial patency
• Granger et al…14124 angiographic observations from 58 studies.
Without fibrinolytic therapy, spontaneous perfusion …15% and 21% at 60 and
90 minutes after study entry, respectively, remains unchanged at 1 day,
then gradually increases to about 60% by 3 weeks.
All fibrinolytic regimens improve early patency rates.
• patency rates at > 3 hours were similar for all regimens, and reocclusion
rates were higher after tPA than non - fibrin specific (systemically active)
agents (13% vs 8%) (P =0.002).
• The GUSTO angiographic study …. early but not late patency rates
accurately predict mortality differences among AMI therapies.
• Studies showing mortality benefit with FT
• GISSI…1st definitive mortality trial..11806 pts….SK vs standard rx.Aspirin
not given.Inhosp mortality [10.7 vs 13%...P 0.0002]…also showed time
dependant benefit
• ISIS-2…17187 pts … SK vs Asp vs both vs placebo…35 d mort reduced by 23%
by asp .. 25 % by SK42 % by both..all P <0.00001
• ASSET study…tPA vs heparin..30 d mort 7.2 vs 9.8 % P 0.0011
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• Fibrinolytic Therapy Trialists Collaborative Group …. database from nine
controlled trials…58600 pts of whom 6177 (10.7%) died, 564 (1.0%) had
strokes, and 436 had major non - cerebral bleeds.
The 45000 patients who presented with STE or BBB had an absolute
mortality reduction of 30 per 1000 for Rx within the first 6 hours, 20/1000
for hrs 7 – 12, and a statistically uncertain reduction of 13 per 1000 beyond
12 hours.
• These data led to the national guidelines ( Class I, Level A ) that all STEMI
patients should undergo rapid evaluation for reperfusion therapy and
have a reperfusion strategy implemented promptly after contact with
the medical system.
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• Those with BBB & Ant STE
benefit the most with FT.
• Those with normal ECGs or
with ST depression alone
showed no benefit and adverse
trends (7 and 14 more deaths
per 1000, respectively).
• The magnitude of mortality
reductions in FTT was
dependent on time to therapy
from symptom onset.
• For those with STE or BBB, the
absolute benefit was 39 (0 –1
h), 30( >1–3 h), 27( >3-6 h),
21(>6–12 h) & 7 (>12–24h) lives
saved /1000 treated
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mortality in each subgroup of fibrinolytic treated (black
bars) versus placebo - treated
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Very early therapy can even abort a myocardial infarction.
Role of fibrinolytic therapy in the prehospital setting.
So the ACC/AHA guidelines have given a indication ( Class IIa, Level A) for
the establishment of a prehospital fibrinolysis protocol in
(1) settings in which physicians are present in the ambulance or
(2) well - organized EMS systems with full - time paramedics who have 12
- lead ECGs in the field with transmission capability, paramedic initial
and ongoing training in ECG interpretation and STEMI treatment, on line medical command, a medical director with training/experience in
STEMI management, and an ongoing continuous quality improvement
program.
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The benefit of fibrinolysis after 6 hours is less certain
• LATE study….5711 pts …MI 6 - 24 hours …tPA (100 mg over 3h) or placebo.
A 26% relative mortality reduction (8.9% vs 11.9%, P= 0.02) was observed
for those treated within 12 hours. The 12 – 24 hour subgroup showed a
non - significant trend to benefit (8.7% vs 9.2% mortality rate).
• The South American EMERAS collaborative group ….4534 pts with IV SK or
placebo within 24 hours after suspected AMI and found a non - significant
trend towards a mortality benefit b/n 7 &12 hrs (SK 11.7%, placebo 13.2%).
This provides the rationale for recommending FT 7-12 hrs group with
persistent symptoms and ECG changes.
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CONTRAINDICATIONS for FT
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• Risks of FT
ICH is the most imp risk, occurring in about 0.5 – 1.0% ….risk of fatality (44 –
75%). MC with fibrin selective agents
7 predictors of ICH [GUSTO-1 group]….advanced age, lower weight, h/o
cerebrovascular disease, h/o hypertension, higher SBP/DBP on
presentation, and randomization to tPA (vs SK). In contrast, the incidence
of non cerebral bleeding is higher with SK.
Allergy, hypotension, and fever
Anaphylaxis or bronchoconstriction is rare ( < 0.2 – 0.5%).
SK may acutely release bradykinin, a vasodilator.
The incidence of clinical hypotension after SK (11.8%) was greater than after
tPA (7.1 %);
Repeat thrombosis and its associated reinfarction is a known, potentially
devastating risk after fibrinolytic therapy.
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• Comparative fibrinolytic trials :
• ASSENT – 2………compared weight - adjusted TNK (as a 30 – 50 mg bolus
over 5 – 10 seconds) and accelerated rt - PA. All patients received aspirin
and heparin. 30 day mortality rates were virtually identical [6%]..
A lower mortality rate with TNK - tPA was observed among patients
presenting 4 hours after symptom onset (7.0% vs 9.2%), which may be due
to either greater activity of the more fibrin - specific TNK - tPA against
older, fibrin - rich clots or chance.
• GISSI-2…..ISIS-3…..tPA vs SK….mortality rates at 35 days were similar
• GUSTO…. The primary endpoint, 30 - day mortality, was lowest with
accelerated tPA with IV heparin compared to SK with IV/SC heparin
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• FT in elderly :
Analyses restricted to elderly patients with clear indications for fibrinolytic
therapy suggested similar or greater absolute benefit vs younger patients.
? Safety concerns……..SK, which carries a lower risk of ICH, or PCI should be
considered as preferred reperfusion strategies in the elderly.
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• Fibrinolysis
• CLASS I
• symptom onset within the prior 12 hours. [A]
• symptom onset within the prior 12 hours and new or presumably new left
bundle branch block (LBBB). [A]
• CLASS II a
• symptom onset within the prior 12 hours and 12-lead ECG findings
consistent with a true posterior MI. [C]
• symptoms of STEMI beginning in the prior 12 to 24 hours who have
continuing ischemic symptoms and ST elevation > 0.1 mV in ≥ 2 contiguous
precordial leads or ≥ 2 adjacent limb leads. [B]
• CLASS III
• initial symptoms of STEMI began more than 24 hours earlier
• 12-lead ECG shows only ST-segment depression, except if a true posterior
MI is suspected.
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Assessment of Reperfusion after fibrinolysis
It is reasonable [Class IIa ] to monitor
• the pattern of ST elevation,cardiac rhythm and clinical symptoms over the
60 to 180 mts after initiation of fibrinolytic therapy.
Noninvasive findings s/o reperfusion include:
 Relief of symptoms
 Maintenance and restoration of hemodynamic and/or electrical instability
 Reduction of ≥ 50% of the initial STE pattern on follow-up ECG 60 to 90
minutes after initiation of therapy.
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 PCI vs Fibrinolysis for STEMI:
 early randomized trials tended to favor direct balloon angioplasty over fi
brinolysis in certain settings. [PAMI…395 pts…with in 12 hrs …PCI vs tPA …
PCI reduced the composite outcome].
 In a meta analysis of 23 randomized STEMI trials comparing primary PCI
with FT, significant reductions in short - term (4 – 6 weeks) and long term
(6 – 8 months) mortality, non - fatal MI, and stroke were seen. Regardless
of whether the fibrinolytic was fibrin specific,primary pci showed similar
benefit.
 Greatest benefit with pci is seen in high risk settings as in Cardiog shock..
as shown in SHOCK trial…302 pts with CS….emergency revascularsn vs
medical stabilisn….Significant mortality reduction is seen @ 6 months 50%
vs 63 %... P 0.03.
• As the delay for performing PCI increases, the mortality benefit for primary
PCI over fibrinolysis decreases. Compared with a fibrin - specific lytic
agent, a PCI strategy may not reduce mortality when a delay > 60 minutes
is anticipated vs immediate FT [Nallamothu et al JACC 2003]
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TYPE OF REPERFUSION THERAPY ?
STEP 1….. Assess Time and Risk
(a)Time Since Symptom Onset
(b)Risk of STEMI….TIMI RISK SCORE…Mortality benefit with PCI is high in pts at
highest mortality risk.So as the risk decreases the mort benefit also decreases
such that mort adv vs FT wont be seen in pts with estimated 30 d mort rate
b/w 2-3%.
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(c)Risk of fibrinolysis…(Risk factors for ICH ….increased age, low body
weight, and hypertension on admission)….when no PCI is available, FT
should still be favored over no reperfusion until the risk of a lifethreatening bleed exceeds 4 %.
(d)Time to reach a skilled PCI lab
• If presentation is < 3 hours and there is no delay to an invasive strategy,
there is no preference for either strategy.
• Fibrinolysis generally preferred
1. Early presentation ( ≤ 3 hours from symptom onset) and delay to invasive
strategy
2. Invasive strategy not an option
 Cath lab occupied or not available
 Vascular access difficulties
 No access to skilled PCI lab
3. Delay to invasive strategy
 Prolonged transport
 Door-to-balloon more than 90 minutes
 > 1 hour vs fibrinolysis (fibrin-specific agent) now
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• Invasive strategy generally preferred
Skilled PCI lab available with surgical backup [Team experience greater
than a total of 36 Primary PCI cases/yr & Operator experience > a total of
75 primary PCI cases/yr].
Door-to-balloon < 90 minutes
(Door-to-Balloon) – (Door-to-Needle) is <1 hour
High Risk from STEMI
 Cardiogenic shock, Killip class ≥ 3
Contraindications to fibrinolysis, including increased risk of bleeding (ICH)
Late presentation … > 3 hours from symptom onset
Diagnosis of STEMI is in doubt
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 Primary PCI…CLASS I [A]
 Patient with STEMI (including posterior MI) or MI with new or presumably
new LBBB
 PCI of infarct artery within 12 hours of symptom onset
 Balloon inflation within 90 minutes of presentation
 Skilled personnel available (individual performs > 75 procedures per year)
 Appropriate lab environment (lab performs > 200 PCIs/year of which at
least 36 are primary PCI for STEMI)
 Cardiac surgical backup available
 CLASS I [B]
 Medical contact–to-balloon or door-to-balloon should be within 90 minutes.
 PCI preferred if > 3 hours from symptom onset
 Severe CHF and/or pulmonary edema and onset of symptoms within 12 hrs.
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• CLASS II a [C]
• onset of symptoms within the prior 12 to 24 hours and 1 or more of the
following:
• a. Severe CHF
• b. Hemodynamic or electrical instability
• c. Persistent ischemic symptoms.
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PCI for Cardiogenic Shock
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• Primary PCI in Cardiogenic shock
• CLASS I …patients less than 75 years old with ST elevation or LBBB who
develop shock within 36 hours of MI and are suitable for revascularization
that can be performed within 18 hours of shock.
• CLASS II a … Those >75 years with ST elevation or LBBB who develop shock
within 36 hours of MI and are suitable for revascularization that can be
performed within 18 hours of shock.
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PCI After Fibrinolysis
In patients whose anatomy is suitable, PCI should be performed for the
following: ie CLASS I

Objective evidence of recurrent MI [C]

Moderate or severe spontaneous/provocable myocardial ischemia during
recovery from STEMI [B]

Cardiogenic shock or hemodynamic instability [B]
CLASS IIa ...routine PCI in patients with left ventricular ejection fraction
(LVEF) ≤ 0.40, CHF, or serious ventricular arrhythmias.
CLASS IIa ...documented clinical heart failure during the acute episode, even
though subsequent evaluation shows preserved LV function (LVEF >
0.40).
CLASS IIb Routine PCI might be considered as part of an invasive strategy after
fibrinolytic therapy. [B]
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• Direct stenting vs FT…..Schomig et al, Le May et al, Kastrati et
al….superior outcome with stenting
• Primary angioplasty vs primary stenting…meta analyses…no diff in
mortality or renifarction..but MACE was reduced due to reduction in TVR
with stenting
• DES vs BMS…..DES signif reduce restenosis,TVR …
• Trials showing the safety of DES
…TYPHOON,PASSION,SESAMY,MULTISTRATEGY trials..
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Facilitated PCI
Facilitated PCI using regimens other than full-dose fibrinolytic therapy might
be considered as a reperfusion strategy when all of the
following are present:
a. Patients are at high risk,
b. PCI is not immediately available within 90 minutes, and
c. Bleeding risk is low (younger age, absence of poorly controlled
hypertension, normal body weight).
A planned reperfusion strategy using full-dosefibrinolytic therapy followed by
immediate PCI is not recommended and may be harmful.
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Intracoronary aspiration/ thrombectomy devices
Signifi cant clot burden may complicate acute STEMI
management. Prospective clinical studies have shown that
intracoronary thrombectomy and thrombus aspiration may
improve TIMI - 3 fl ow, hasten ST segment elevation resolution,
and enhance myocardial tissue perfusion and reduce MI.
TAPAS trial…pts randomized to initial aspiration thrombectomy
vs standard PCI regardless of the presence or absence of
angiographically visible thrombus. At 1yr follow - up, cardiac
death was 3.6% (19 of 535) vs 6.7% (36 of 536) (P=0.020).
One - year cardiac death or non - fatal reinfarction occurred in
5.6% (30 of 535) vs 9.9% (53 of 536) of patients in the
conventional PCI group (P=0.009).
So when performing primary PCI for STEMI, aspiration
thrombectomy prior to balloon inflation should be performed
whenever possible.
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Embolization protection devices…. no benefit has been found when
applied to native vessels in the setting of STEMI
• DEDICATION Trial….626 patients with STEMI and undergoing primary PCI
were randomized to distal protection using the FilterWire or standard
therapy. There was no significant difference in the occurrence of the
primary endpoint of complete ( = 70%) ST segment resolution (76% vs 72%,
P= 0.29), no difference in maximum troponin - T (4.8 µ g/L and 5 µ g/L, P
=0.87) or maximum CK- MB (185µ g/L and 184 µg/L, P= 0.99), and no
difference in median LV wall motion index (1.70 vs 1.70, P=0.35). The
rate of major adverse cardiac and cerebral events 1 month after PCI was
5.4% with distal protection and 3.2% with conventional treatment
(P=0.17).
• So when performing primary PCI for STEMI, use of distal protection devices
during balloon inflation is not generally recommended ( Class III, Level A).
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• EMERGENCY CABG
•
Class I
a. Failed PCI with persistent pain or hemodynamic instability
b. Persistent or recurrent ischemia refractory to medical therapy ;
have a significant area of myocardium at risk, and are not candidates for
PCI or fibrinolytic therapy.
c. At the time of surgical repair of postinfarction VSR or MR
d. Cardiogenic shock in pts <75 years old with STE/LBBB/PW MI
who develop shock within 36 hrs of STEMI, have severe multivessel or
left main disease, and are suitable for revascularization that can be
performed within 18 hrs of shock, unless further support is futile
because of the patient’s wishes or contraindications/unsuitability for
further invasive care.
e. Life-threatening ventricular arrhythmias in the presence of > 50%
LMCA stenosis &/or TVD
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Class IIa
• Can be useful as primary reperfusion strategy in patients who have
suitable anatomy, who are not candidates for fibrinolysis or PCI, and
who are in the early hours (6 to 12 hours) of an evolving STEMI, esp if
severe multivessel or LMCA disease is present.
• can be effective in selected pts 75 years or older with STE/LBBB/PW MI
who develop shock within 36 hrs of STEMI, have severe multivessel or
left main disease, and are suitable for revascularization that can be
performed within 18 hrs of shock.
Class III
• persistent angina and a small area of risk if they are
hemodynamically stable.
• successful epicardial reperfusion but unsuccessful microvascular
reperfusion.
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• ANCILLARY THERAPY TO REPERFUSION
• Anticoagulants….
• more prolonged anticoagulant therapy…..beneficial… (duration of index
hospitalization) in pts receiving fibrinolytics, as seen in the comparisons of
reviparin versus placebo (CREATE), fondaparinux versus placebo (OASIS-6),
and enoxaparin versus UFH (ExTRACT-TIMI 25).
• The mechanism of benefit from a more prolonged regimen ….includes a
longer exposure to anticoagulants to prevent rethrombosis of the infarct
artery and prevention of the rebound increase in events seen after abrupt
discontinuation of UFH infusions.
• Overall, UFH does not appear to improve early (60 – 90 mt) IRA patency.
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UFH in those on FT : FT release of plasmin..activates platelets
; also triggers thrombin generation via factor V activation.
As the free plasmin activity increases (SK),prothrombotic effect
will be more marked..
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• UFH in primary PCI :
• There are no large - scale data to guide the use of UFH in PCI
and thus it remains relatively empiric. The existing data are
from small scale studies from pts undergoing elective
procedures.. A meta - analysis of six RCTs suggested optimal
benefit with an initial bolus of 70 – 100 U/kg aiming for an
ACT of 350–375 s. In patients treated with a Gp IIb/IIIa
receptor antagonist, this should be reduced to 50 – 70 U/kg,
aiming for an ACT of 200 s.
• LMWH : advantages …more predictable level of
anticoagulation & so no need for mandatory laboratory
monitoring; a reduction in the incidence of thrombocytopenia,
less platelet activation and an easier route of administration.
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• LMWH in pts receiving FT : Trials taken together …. suggest a
modest advantage of LMWH over UFH that appears to be d/t
enhanced late patency of the infarct - related vessel and an
associated reduction in reinfarction rate.
• CREATE Trial… Reviparin vs placebo x 7d.. 15000 STEMI
pts…India & China….Primary endpoints of death,MI,stroke was
reduced in those treated with reviparin vs placebo at 7 days
(9.6 vs 11 %; P=0.0049) and 30 days (11.8% versus 13.6%, P
= 0.0014).
ASSENT - 3 trial… 6095 pts were randomized to full - dose TNK +
UFH for at least 48 hours, full - dose TNK with enoxaparin x 7d
or reduced - dose TNK with abciximab and UFH. The
composite of death, reinfarction or refractory ischemia was
significantly lower in those treated with enoxaparin than UFH
(P=0.0002). This advantage was primarily d/t a reduction in
the rate of reinfarction. However, there was an increased
incidence of bleeding complications in those treated with
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enoxaparin compared to UFH
ExTRACT - TIMI 25 trial :
Randomized 20506 pts with STEMI undergoing fibrinolysis to receive either
enoxaparin (30 mg IV bolus followed by 1 mg/kg throughout the index
hospitalization) or UFH (60 U bolus followed by 12 U/kg/h for 48 hours).
The primary endpoint of death or reinfarction at 30 days occurred in 12.0%
(UFH) and 9.9% (enoxaparin) P<0.001. TIMI major bleeding was increased
in the enoxaparin group vs UFH (2.1% vs 1.4%, P<0.001) whilst rates of ICH
were similar (0.8% vs 0.7% respectively..P=0.14).
Impaired Renal function ((CrCl<90 mL/min) were a/w increased bleeding
So…..LMWHs are a useful alternative to UFH in STEMI in conjunction with FT
and should be administered throughout the index hospitalization (up to
eight days) ( Class I, Level A).
LMWH in pts Rxed with primary PCI : There are limited data regarding
the safety and efficacy of LMWHs during PCI in the context of STEMI.
[LMWHs are a reasonable alternative to UFH in patients with STEMI
undergoing primary PCI ( Class IIb, Level B).]
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Direct Thrombin Inhibitors
Bivalirudin : HERO-1 trial..412 pts… UFH vs low dose bivalirudin (0.125mg/kg
bolus followed by a 0.25 mg/ kg/h infusion for 12 h, then 0.125
mg/kg/h) vs high - dose bivalirudin (0.25 mg/kg bolus followed by a 0.5
mg/kg/h infusion for 12 h, then 0.25 mg/kg/h).
TIMI 3 flow at 90 – 120 mts was higher following bivalirudin than UFH (48%
with high dose bivalirudin, 46% with low dose bivalirudin and 35% with
UFH, P=0.024).
Larger HERO - 2 trial randomized 17073 pts to receive a bolus and 48 h
infusion of bivalirudin or UFH immediately prior to SK. At 30 days,
mortality was similar.
ARGAMI-2 trial….1001 pts to UFH or argatroban (Univalent DTI) (120µg bolus
followed by a 4µg/kg/ min infusion for 72h) in addition to fibrinolysis with
SK or alteplase. A third treatment arm consisting of half - dose argatroban
was terminated prematurely due to lack of effi cacy. Mortality at 30 days
was similar (5.5% in the argatroban group versus 5.7% in UFH group,P=ns).
Meta -analysis of DTI trials[UFH vs DTI] (by DTI Trialists Collaborative
Group)…. No diff in mort was seen at cessation of Rx/7d/30d/6 months,
but signif reduction in incidence of reinfarction /combined incidence of
death/MI were seen.
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So Bivalirudin is a useful alternative to UFH in STEMI along with FT..Class I
DTI in primary PCI
HORIZONS-AMI trial….3600 STEMI pts undergoing primary PCI …UFH + GpIIbIIIaVS Bivalirudin. There was a reduction in overall clinical events (a
composite of major bleeding and MACE) in the bivalirudin group at 30 days
compared to the UFH and glycoprotein IIb/IIIa receptor antagonist group
(12.1% versus 9.2% respectively, P = 0.006).
Major bleeding alone at 30 days was also substantially reduced (8.3% versus
4.9%, P<0.0001) and there was a signifi cant reduction in cardiac death at
30 days (2.9% versus 1.8%, P = 0.035).
The initial data demonstrate an excess in adverse events with bivalirudin only
within the first 24 hours, probably related to an excess incidence of early
stent thrombosis (1.3% versus 0.3% with UFH and glycoprotein IIb/IIIa
receptor antagonist). However, the subsequent reduction in events seen in
those treated with bivalirudin results in an overall benefit in favor of
bivalirudin at 30 days, likely to be driven by a reduction in bleeding
complications.
Bivalirudin is a reasonable alternative to the combination of UFH and a
glycoprotein IIb/IIIa receptor antagonist in patients with STEMI undergoing
primary PCI ( Class IIa, Level B ).
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Fondaparinux:
Based upon the results from OASIS trials….Fondaparinux is a useful alternative
to UFH in STEMI patients who have received fibrinolytic therapy ( Class I,
Level B )
Fondaparinux should not be used as the sole anticoagulant in patients with
STEMI undergoing primary PCI ( Class III, Level B)…
OASIS-6 trial
1) benefit of fondaparinux vs UFH or placebo on the primary endpoints of
death and recurrent MI in pts on FTwas not seen in patients undergoing
primary PCI
2)d/t higher rate of guiding catheter thrombosis & more coronary
complications (abrupt coronary closure,new angiographic
thrombus,catheter thrombus,no reflow,dissection or perforation)
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• Ancillary Therapy to Reperfusion
UFH should be given [CLASS I] intravenously in:
 Patients undergoing PCI or surgical revascularization [C]
 After alteplase, reteplase, tenecteplase [C]
 After streptokinase, anistreplase, urokinase in patients at high risk for
systemic emboli [B]
 CLASS I Platelet counts should be monitored daily in pts taking UFH [C]
 CLASS IIb LMWH might be considered an acceptable alternative to UFH in
pts less than 75 years who are receiving fibrinolytic therapy in the absence
of significant renal dysfunction. [B]…..Enoxaparin used with tenecteplase
is the most comprehensively studied.
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• Other Pharmacological Measures
•
Angiotensin converting enzyme inhibitors
•
Angiotensin receptor blockers (ARB)
•
Aldosterone blockers
•
Glucose control
•
Magnesium
•
Calcium channel blockers
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• ACE/ARB: Within 24 Hours
• An ACE inhibitor should be administered orally within the first 24 hours of
STEMI to the following patients without hypotension or known class of
I IIa IIb III
contraindications:Anterior infarction,
pulmonary congestion,
LVEF < 0.40.
• An ARB should be given to ACE-intolerant patients with either clinical or
I IIa IIb III
radiological signs of HF or LVEF < 0.40.
• An intravenous ACE inhibitor should not be given to patients within the
I IIa IIb III
first 24 hours of STEMI because of the risk of hypotension
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• Strict Glucose Control During STEMI
• An insulin infusion to normalize blood glucose is recommended for patients
I IIa IIb III
and complicated courses.
• It is reasonable to administer an insulin infusion to normalize blood glucose
I IIa IIb III
even in patients with an uncomplicated course.
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63
Right Ventricular Infarction
Hemodynamics:
Increased RA pressure (y descent)
Square root sign in RV tracing
Rx:
Maintain RV preload
Lower RV afterload (PA---PCW)
Inotropic support
Reperfusion
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• Secondary Prevention and Long Term
Management
• Smoking Goal: Complete Cessation
• Blood pressure control:
• Goal: < 140/90 mm Hg or <130/80 mm Hg if
chronic kidney disease or diabetes
• Physical activity:Minimum goal:30 minutes 3
to 4 days per week;Optimal daily
65
• Weight management:
• Goal:
BMI 18.5 to 24.9 kg/m2
• Waist circumference: Women: < 35 in. Men: < 40 in.
• Diabetes management: Goal: HbA1c < 7%
66
Lipid management:
TG <200 mg/dL
Primary goal:LDL-C << than 100 mg/dL
Start dietary therapy in all patients (< 7% of total calories as saturated fat and
< 200 mg/d cholesterol). Promote physical activity and weight management.
Encourage increased consumption of omega-3 fatty acids.
Assess fasting lipid profile in all patients, preferably within 24 hours of STEMI.
TG 200 mg/dL or greater : Primary goal: Non–HDL-C << 130 mg/dL
TGs ≥ 150 mg/dL or HDL-C < 40 mg/dL:
Emphasize weight mgt and physical activity. Advise smoking cessation.
TG 200 to 499 mg/dL:
After LDL-C–lowering therapy, consider adding fibrate or niacin.
TG ≥ 500 mg/dL:
Consider fibrate or niacin before LDL-C–lowering therapy.
Consider omega-3 fatty acids as adjunct for high TG.
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• Hormone therapy with estrogen plus progestin should not be given de novo
to postmenopausal women after STEMI for secondary prevention I IIa IIb III
of coronary events.
• Postmenopausal women who are already taking estrogen plus progestin at
the time of STEMI should not continue hormone therapy.
I IIa IIb III
• However, women who are beyond 1 to 2 years after initiation
of hormone therapy who wish to continue such therapy for another
compelling indication should weigh the risks and benefits.
• Antioxidant vitamins such as vitamin E and/or vitamin C supplements
should not be prescribed to patients recovering from STEMI to prevent
cardiovascular disease.
I IIa IIb III
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• The psychosocial status of the patient should be evaluated, including
inquiries regarding symptoms of depression, anxiety, or sleep disorders and
I IIa IIb III
the social support environment.
• Treatment with cognitive-behavioral therapy and selective serotonin
reuptake inhibitors can be useful for STEMI patients with depression that
occurs in the year after hospital discharge.
I IIa IIb III
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HAPPY NEW YEAR
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