1. UPDATES IN THE MANAGEMENT
OF STEMI
2013-ACCF/AHA GUIDELINES
2015 AHA Focused Update on. Primary
PCI 2017-European Society of
Cardiology
BY:
DR DARAYUS P. GAZDER
PG Resident Year 1
2. EPIDEMIOLOGY
•In 2009, nearly 683,000 patients were
discharged from U.S. hospitals with a
diagnosis of ACS.
•Incidence rates for STEMI have declined over
the past decade, whereas those for non–ST-
elevation ACS have increased.
•At present, STEMI comprises approximately
25% to 40% of MI presentations.
3.
4.
5. ESC guidelines:
1)ST-segment elevation ≥ 2.5mm in men < 40years, ≥2mm in men ≥ 40years, or≥1.5mm
in women in leads V2–V3 and/or ≥ 1mm in the other leads [in the absence of left
ventricular (LV) hypertrophy or left bundle branch block LBBB)
2) In patients with inferior MI, it is recommended to record right precordial leads (V3R and
V4R) seeking ST-segment elevation, to identify concomitant right ventricular infarction(RV)
infarction
15. REPERFUSION AT A PCI-
CAPABLE HOSPITAL
2) ASPIRATION
THROMBECTOMY AND
RECENT ADVANCES
16. ASPIRATION THROMBECTOMY
2013 ACCF/AHA guidelines recommend routine
thrombus aspiration before primary PCI in STEMI
(Class IIa) based on the available evidence
supporting this therapy.
I IIa IIb III
17.
18. REPERFUSION AT A
PCI- CAPABLE
HOSPITAL
3) USE OF STENTS IN
PATIENTS WITH STEMI
AND RECENT ADVANCES
19. Placement of a stent (BMS or DES)
is useful in primary PCI for patients
with STEMI.
I IIa IIb III
BMS* should be used in patients with high
bleeding risk, inability to comply with 1
year of DAPT, or anticipated invasive or
surgical procedures in the next year.
I IIa IIb III
20. DES have been shown to have superior efficacy as compared to
bare metal stents (BMS), concerns regarding safety with DES
due to incomplete endothelialization and inflammation eventually
leading to a potentially higher risk of stent thrombosis
21. • Second generation EVEROLIMUS ELUTING XIENCE V
stents were associated with a lower incidence of stent
thrombosis, target vessel revascularization and major
adverse cardiac events as compared to BMS and older
SIROLIMUS ELUTING STENTS after PCI in patients
with acute myocardial infarction.(A)
A) Sabate M, Cequier A, Iñiguez A, Serra A et al:Everolimus-eluting stent versus bare- metal stent in ST-segment
elevation myocardia infarction (EXAMINATION): 1 year results of a randomise controlled trial. Lancet 2012,
380:1482-90]
B) Park KW, Lee JM, Kang S, et al: Safety and efficacy of second-generation everolimus- eluting Xience V stents
versus zotarolimus-eluting resolute stents in real-world practice: patient-related and stent-related outcomes from
the multicenter prospective EXCELLENT and RESOLUTE-Korea registries. J Am Coll Cardiol 2013, 61:536-44
C) Birgelen C von, Basalus MWZ, Tandjung Ket al: Arandomized controlled trial in second- generation zotarolimus
eluting Resolute stents versus everolimus-eluting Xience V stents in real-world patients: theTWENTE trial. J Am
Coll Cardiol 2012, 59:1350-61
• Newer second generation ZOTAROLIMUS eluting
resolute stents are also undergoing trials. [B,C]
22. • DES with biodegradable polymers have also
emerged and were compared with BMS in 1,161
patients with AMI in the COMFORTABLE trial.
• The primary endpoint (composite of cardiac
death, target vessel re-infarction and ischemia
driven target lesion revascularization) was lower
in the biolimus stent, driven mostly by a
substantial reduction of 80% in the incidence of
target vessel reinfarction.
• There is a trend towards a lower rate of stent
thrombosis in patients with biolimus DES.
Circ Cardiovasc Interv. 2014 Jun;7(3):355-64. doi: 10.1161/CIRCINTERVENTIONS.113.001440. Epub 2014
May 20.Biolimus-eluting stents with biodegradable polymer versus bare-metal stents in acute myocardial
infarction: two-year clinical results of the COMFORTABLE AMI trial.Räber L1
,
23. REPERFUSION AT A PCI-
CAPABLE HOSPITAL
•4) ANTIPLATELET THERAPY TO
SUPPORT PRIMARY PCI FOR
STEMI AND RECENT
•ADVANCES
24.
25.
26. ADJUNCTIVE ANTITHROMBOTIC THERAPY TO
SUPPORT REPERFUSION WITH PRIMARY PCI
(CONT.)
*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.
†Balloon angioplasty without stent placement may be used in selected patients. It might be reasonable to provide P2Y12
inhibitor therapy to patients with STEMI undergoing balloon angioplasty alone according to the recommendations listed
for BMS. (LOE: C).
27.
28.
29.
30.
31. REPERFUSION AT A PCI-
CAPABLE HOSPITAL
• 5) ANTICOAGULANT THERAPY TO
SUPPORT PRIMARY PCI AND
RECENT ADVANCES
34. REPERFUSION AT A NON–PCI
CAPABLE HOSPITAL
1) FIBRINOLYTIC THERAPY WHEN
THERE IS AN ANTICIPATED DELAY TO
PERFORMING PRIMARY
PCI WITHIN 120 MINUTES OF FMC
36. REPERFUSION AT A
NON– PCI CAPABLE
HOSPITAL
2) ADJUNCTIVE ANTITHROMBOTIC
THERAPY WITH FIBRINOLYSIS
37. Aspirin (162- to 325-mg loading dose)
and clopidogrel (300-mg loading dose for
patients ≤75 years of age,
75-mg dose for patients >75 years of
age) should be administered to patients
with STEMI who receive fibrinolytic
therapy.
I IIa IIb III
38. In patients with STEMI who receive
fibrinolytic therapy:
I IIa IIb III
• Aspirin (81mg per day) should be
continued indefinitely and
• clopidogrel (75 mg daily) for at least
14 days
• and up to 1
year
I IIa IIb III
I IIa IIb III
39. REPERFUSION AT A NON– PCI-
CAPABLE HOSPITAL
• 3) ADJUNCTIVE ANTICOAGULANT
THERAPY WITH FIBRINOLYSIS
40. I IIa IIb III
Patients with STEMI undergoing
reperfusion with fibrinolytic therapy
should receive anticoagulant therapy
for a minimum of 48 hours, and
preferably for the duration of the index
hospitalization, up to 8 days or until
revascularization if performed.
41. a. UFH adm. as a weight-adjusted
intravenous bolus and infusion to
obtain an aPTT time of 1.5 to 2.0 times
control, for 48 hours or until
revascularization;
b. Enoxaparin adm. a/c to age, weight,
and creatinine clearance, given as an
i.v bolus, followed in 15 min. by s/c inj.
for the duration of the index
hospitalization, up to 8 days or until
revascularization; or
I IIa IIb III
I IIa IIb III
Recommended regimens
include:
42. • Fondaparinux administered with initial
i.v dose, followed in 24 hrs by daily s/c
inj. if the estimated creatinine clearance
is greater than 30 mL/min, for the
duration of the index hospitalization, up
to 8 days or until revascularization.
I IIa IIb III
45. INDICATIONS FOR CORONARY ANGIOGRAPHY
IN
PATIENTS
WHO WERE MANAGED WITH FIBRINOLYTIC
THERAPY OR WHO DID NOT RECEIVE
REPERFUSION THERAPY
(ST-segment resolution < 50% within 60–90min)
47. Urgent CABG is indicated in patients
with STEMI and coronary anatomy not
amenable to PCI who have ongoing or
recurrent ischemia, cardiogenic shock,
severe HF, or other high-risk features.
CABG is recommended in patients
with STEMI at time of operative
repair of mechanical defects.
I IIa IIb III
I IIa IIb III
48. Timing of Urgent CABG in
Patients With STEMI in
Relation to Use of Antiplatelet
Agents
49. Aspirin should not be with held
before urgent CABG.
Short-acting intravenous GP IIb/IIIa
receptor antagonists should be
discontinued at least 2 to 4 hours before
urgent CABG.
Clopidogrel or ticagrelor should be
discontinued at least 24 hours before
urgent on-pump CABG, if possible.
I IIa IIb III
I IIa IIb III
I IIa IIb III
54. MONOCLONAL ANTIBODIES:
INCLACUMAB
• SELECT–ACS trial examined P-selectin
monoclonal antibody, in patients with NSTE–
ACS undergoing PCI .
• 544 NSTEMI patients scheduled for PCI to a
placebo infusion or to either a 5 mg/kg or
20mg/kg infusion of INCLACUMAB.
• There were reductions in troponin I levels at 24
hours after the 20 mg/kg infusion as compared
to placebo, suggesting potential for reducing
myocardial damage.
Tardif J, Tanguay J, Wright SS, et al: Effects of the P-selectin antagonist
inclacumab on myocardial damage after percutaneous coronary intervention for
non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial.
J Am Coll Cardiol 2013, 61:2048-55
55. STEM CELL THERAPY
• The use of stem cells derived from bone marrow
or myocardium to improve cardiac function has
been promising.
• The phase 1 CADUCEUS trial enrolled 30
patients with recent MI and reduced ejection
fraction (25%–45%) and randomized them in a
2:1 ratio to receive autologous cardiac stem cells
derived from endomyocardial biopsy (within 1.5–
3 months after myocardial infarction) or placebo.
Makkar RR, Smith RR, Cheng K et al: Intracoronary cardiosphere-derived cells for
heart regeneration after myocardial infarction (CADUCEUS): a prospective,
randomised phase 1 trial. Lancet 2012, 379:895-904
56. • Although there were no improvements in ejection
fraction at 12 months but there was a significant
decrease in myocardial scar tissue and an
increase in viable myocardium (based on cardiac
MRI) in the intervention group, as compared to
placebo.
Traverse JH, Henry TD, Pepine CJ et al.: Effect of the use and timing of bone
marrow mononuclear cell delivery on left ventricular function after acute myocardial
infarction: the TIME randomized trial. JAMA 2012, 308:2380-9
•Two trials—the ALLSTAR (allogenic cardiac stem
cells) and BAMI (autologous bone marrow cells)—
are currently enrolling patients and are underway.
STEMI represents the most lethal form of ACS, in which a completely occlusive thrombus typically results in total cessation of coronary blood flow, manifested electrically as elevation of the ST segment on the ECG.
Patients with a clinical suspicion of ongoing myocardial ischaemia and LBBB should be managed in a way similar to STEMI patients, regardless of whether the LBBB is previously known.
Level of evidencThe term acute myocardial infarction (AMI) should be used when there is evidence of myocardial injury (defined as an elevation of cardiac troponin values with at least one value above the 99th percentile upper reference limit) with necrosis in a clinical setting consistent with myocardial ischaemia
e
Modes of patient presentation, components of ischaemia time and flowchart for reperfusion strategy selection. EMS = Emergency Medical System; FMC = First Medical Contact; PCI = Percutaneous Coronary Intervention; STEMI = ST-segment elevation myocardial infarction.
The recommended mode of patient presentation is by alerting the EMS (call national emergency number: 112 or similar number according to region). When STEMI diagnosis is made in the out-of-hospital setting (via EMS) or in a non-PCI centre, the decision for choosing reperfusion strategy is based on the estimated time from STEMI diagnosis to PCI-mediated reperfusion (wire crossing). System delay for patients alerting the EMS starts at the time of phone alert, although FMC occurs when EMS arrives to the scene (see Table 4). ´denotes minutes. aPatients with fibrinolysis should be transferred to a PCI centre immediately after administration of the lytic bolus.
Indication for PCI in non-IRA was angiography-guided in lesions with ≥50% stenosis (PRAMI), &gt;70% stenosis…Multivessel disease is common (in approximately 50%) in patients with STEMI
The TASTE trial enrolled 7244 patients with STEMI randomized them to routine thrombus aspiration or no thrombus aspiration before primary PCI*.
There were no differences in all cause mortality at the end of 30 days (2.8% vs. 3.0%; P = 0.63).
There was a trend towards a reduction in hospitalizations for recurrent myocardial infarction and incidence of stent thrombosis.
DES should not be used in primary PCI for patients with STEMI who are unable to tolerate or comply with a prolonged course of DAPT because of the increased risk of stent thrombosis with premature discontinuation of one or both agents.
While DES have been shown to have superior efficacy as compared to bare metal stents (BMS), there have been concerns regarding safety with DES due to incomplete endothelialization and inflammation eventually leading to a potentially higher risk of stent thrombosis
After PCI, aspirin should be continued indefinitely.
It is reasonable to start treatment with an intravenous GP IIb/IIIa receptor antagonist at the time of primary PCI (with or without stenting or clopidogrel pretreatment) in selected patients with STEMI who are receiving UFH
The 2 drugs have been compared together in a head-to-head trial called the TRITON-TIMI 38(Trial to assess Improvement in Therapeutic Outcomes by optimizing platelet Inhibition with prasugrel Thrombolysis In Myocardial Infarction 38). In that study, prasugrel actually provided a significant reduction in cardiovascular outcomes. There was a slight increased risk for bleeding that was statistically significant. It was one of those things where they couldn&apos;t have their cake and eat it too: better outcomes but a little more bleeding.
The reason for that is that if you look at the molecule of prasugrel, it&apos;s been shown to provide more potent and much more consistent antiplatelet effect. One of the things we&apos;ve known about clopidogrel is that there is a large variability in effect in ability to inhibit the platelet. We don&apos;t seem to see that as much with prasugrel. If you inhibit the platelet more, you reduce outcomes, but if you inhibit the platelet more, you also have an increased risk for bleeding. Some of that bleeding was pretty severe; life-threatening bleeding was significantly higher and fatal bleeding was significantly higher. Clearly, some things we&apos;d have to think about if we were going to select a patient to get prasugrel.
In fact, 3 groups of patients were definitely found to be at higher risk for bleeding. One is patients who had a history of a transient ischemic attack or a stroke. That is actually a boxed warning -- that those patients should not get prasugrel; it&apos;s a contraindication. Two other groups of patients are those over the age of 75 or those who weigh less than 60 kg. Those patients also are at an increased risk for bleeding. There are not absolute contraindications there but still some real cautions to worry about. We have prasugrel, a drug that provides more potent antiplatelet activity. There are some benefits there but also some safety concerns. Clearly, it&apos;s something that advances where we&apos;ve been with antiplatelet therapy.
Overall, the authors of the PLATO study concluded that, compared with clopidogrel, treatment with ticagrelor significantly reduced the risk of death from vascular causes, MI, or stroke, without increasing the rate of overall major bleeding, but with an increase in the rate of non-procedure-related bleeding.
Ticagrelor and prasugrel, although both newer agents, have not been directly compared in a head-to-head trial. Ticagrelor was compared with clopidogrel, and as Paul mentioned, similar to the prasugrel trial, a significant reduction in cardiovascular death, myocardial infarction (MI), or stroke was demonstrated. It was slightly different in the definition of major bleeding in that study. They had their own PLATO-defined major bleeding, which was not significantly increased with ticagrelor. However, the non- coronary artery bypass graft (CABG) major bleeding still was elevated in the patients receiving ticagrelor, so it&apos;s similar to having more potent platelet inhibition, which ticagrelor does have. Compared with clopidogrel, there was an increased risk for non-CABG major bleeding.
Another significant endpoint that was found in that trial that was a little bit different from the TRITON trial was that there was a significant reduction in cardiovascular mortality. I think that&apos;s what many cardiologists are excited about with that particular drug. Again, that comes with the price of taking the drug twice a day, compared with once a day with clopidogrel and prasugrel
Overall, the authors of the PLATO study concluded that, compared with clopidogrel, treatment with ticagrelor significantly reduced the risk of death from vascular causes, MI, or stroke, without increasing the rate of overall major bleeding, but with an increase in the rate of non-procedure-related bleeding.
In a meta-analysis of 23 PCI trials (30 966 patients, 33% primary PCI), enoxaparin was associated with a significant reduction in death compared to UHF. This effect was particularly significant in the primary PCI context and was associated with a reduction in major bleeding.202 Based on these considerations, enoxaparin should be considered in STEMI.
Previously published resu
lts from randomized trials (HORIZONS– AMI in STEMI) have consistently demonstrated a reduced risk of bleeding and improved overall outcomes with bivalirudin rather than unfractionated heparin (UFH) in ACS patients, giving bivalirudin a CLASS 1B RECOMMENDATION (from ACCF/AHA) as an adjunctive therapy in patients with ACS undergoing primary PCI.
Fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability
It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy.
ROUTINE EARLY PCI
Fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of symptom onset and a large area of myocardium at risk or hemodynamic instability
