FUTURE STRATEGIES AND 2013 ACCF/AHA GUIDELINES FOR

THE MANAGEMENT OF STEMI

PRESENTER: DR ADITYA

MODERATOR: (PROF) DR. ANITA SHARMA

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.

CLASSIFICATION OF RECOMMENDATIONS AND

LEVELS OF EVIDENCE

(Adapted from CW Hamm et al: Lancet 358:1533, 2001, an MJ Davies: Heart 83:361, 2000)

STEMI

• Diagnostic ST elevation in the absence of left ventricular (LV) hypertrophy or left bundle-branch block (LBBB) is defined by the ESC/ACCF/AHA for the Universal Definition of MI as:

new ST elevation at the J point in at least 2 contiguous leads of 2 mm (0.2 mV) in men or 1.5 mm (0.15 mV) in women in leads V2–V3 and/or of 1 mm (0.1 mV) in other contiguous chest leads or the limb leads.

• The majority of patients will evolve ECG evidence of Q-wave infarction.

• New LBBB at presentation interfere with ST-elevation analysis, and not a diagnostic criteria of AMI in isolation.

Community Preparedness and System Goals for

Reperfusion Therapy

REPERFUSION THERAPY FOR PATIENTS WITH STEMI

REGIONAL SYSTEMS OF STEMI CARE, REPERFUSION THERAPY, AND

TIME-TO-TREATMENT GOALS

All communities should create and maintain a regional system of STEMI care.

I IIa IIb III

Performance of a 12-lead ECG by EMS personnel at the site of FMC is recommended in patients with symptoms consistent with STEMI.

I IIa IIb III

Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours.

Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators.

I IIa IIb III EMS transport directly to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI with an ideal FMC-to-device time system goal of 90 minutes or less.*

I IIa IIb III

I IIa IIb III

Immediate transfer to a PCI-capable hospital for primary PCI is the recommended triage strategy for patients with STEMI who initially arrive at or are transported to a non–PCI-capable hospital, with an FMC-to-device time system goal of 120 minutes or less.

In the absence of contraindications, fibrinolytic therapy should be administered to patients with STEMI at non–PCI-capable hospitals when the anticipated FMC-to-device time at a PCI-capable hospital exceeds 120 minutes.

I IIa IIb III

I IIa IIb III

When fibrinolytic therapy is indicated or chosen as the primary reperfusion strategy, it should be administered within 30 minutes of hospital arrival.

Reperfusion therapy is reasonable for patients with STEMI and symptom onset within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia.

I IIa IIb III

I IIa IIb III

REPERFUSION AT A PCI-CAPABLE HOSPITAL

REPERFUSION AT A PCI-CAPABLE HOSPITAL

1) PRIMARY PCI IN STEMI

I IIa IIb III Primary PCI should be performed in patients with STEMI and ischemic symptoms of less than 12 hours’ duration.

Who have contraindications to fibrinolytic therapy, irrespective of the time delay from FMC.

I IIa IIb III

I IIa IIb III Primary PCI should be performed in patients with STEMI and cardiogenic shock or acute severe HF, irrespective of time delay from MI onset.

Primary PCI is reasonable in patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia between 12 and 24 hours after symptom onset.

I IIa IIb III

PCI should not be performed in a non-infarct artery at the time of primary PCI in patients with STEMI who are hemodynamically stable

I IIa IIb III

Harm

PRIMARY PCI IN STEMI

REPERFUSION AT A PCI-CAPABLE HOSPITAL

2) ASPIRATION THROMBECTOMY AND RECENT ADVANCES

ASPIRATION THROMBECTOMY

Current 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

• 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.

* Fröbert O, Lagerqvist B, Olivecrona GK et al: Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013, 369:1587-97

REPERFUSION AT A PCI-CAPABLE HOSPITAL

3) USE OF STENTS IN PATIENTS WITH STEMIAND RECENT ADVANCES

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

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.

I IIa IIb III

Harm

• There has been debate regarding the use of drug eluting stents (DES) in patients with STEMI.

• 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.

• 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.

[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]

• Newer second generation ZOTAROLIMUS eluting resolute stents are also undergoing trials. [A,B]

A)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

B) 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

• 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.

Räber L, Kelbæk H, Ostojic M et al: Effect of biolimus-eluting stents with biodegradable polymer vs baremetal stents on cardiovascular events among patients with acute myocardial infarction: the COMFORTABLE AMI randomized trial. JAMA 2012, 308:777-87

REPERFUSION AT A PCI-CAPABLE HOSPITAL

4) ANTIPLATELET THERAPY TO SUPPORT PRIMARY PCI FOR STEMI AND RECENT

ADVANCES

Aspirin 162 to 325 mg should be given before primary PCI.

After PCI, aspirin should be continued indefinitely.

I IIa IIb III

I IIa IIb III

A loading dose of a P2Y12 receptor inhibitor should be given as early as possible or at time of primary PCI to patients with STEMI:

• Clopidogrel 600 mg; or

I IIa IIb III

• Prasugrel 60 mg; or • Ticagrelor 180 mg

P2Y12 inhibitor therapy should be given for 1 year to patients with STEMI who receive a stent (BMS or DES) during primary PCI using the following maintenance doses:• Clopidogrel 75 mg daily; or

I IIa IIb III

• Prasugrel 10 mg daily; or • Ticagrelor 90 mg twice a day*

*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.

It is reasonable to use 81 mg of aspirin per day in preference to higher maintenance doses after primary PCI.

I IIa IIb III

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.

• Double-bolus EPTIFIBATIDE: 180 mcg/kg IV bolus, then 2 mcg/kg/min; a 2nd 180-mcg/kg bolus is administered 10 min after the 1st bolus.

• ABCIXIMAB: 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min (maximum 10 mcg/min); or

• High-bolus-dose TIROFIBAN: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min; or

I IIaIIb III

I IIaIIb III

I IIaIIb III

It may be reasonable to administer intravenous GP IIb/IIIa receptor antagonist in the precatheterization laboratory setting to patients with STEMI for whom primary PCI is intended.

It may be reasonable to administer intracoronary abciximab to patients with STEMI undergoing primary PCI.

I IIa IIb III

I IIa IIb III

Continuation of a P2Y12 inhibitor beyond 1 year may be considered in patients undergoing DES placement.

I IIa IIb III

Prasugrel should not be administered to patients with a history of prior stroke or transient ischemic attack.

I IIa IIb III

Harm

PRASUGREL

• It was compared to clopidogrel in a randomized trial (TRITON–TIMI 38) for ACS patients who were scheduled to undergo PCI.

• Based on the promising results from this trial (superior efficacy, albeit with a higher bleeding risk), the agent was approved for patients with ACS scheduled to undergo PCI.

• A large proportion of patients with NSTEMI/ UA grouped under NSTE-ACS were however managed medically and didn’t receive early revascularization.(TRILOGY ACS trial).

• This study randomized 9,326 patients with NSTE–ACS to receive either prasugrel or clopidogrel. At a median follow up of 1.7 years, the results were neutral with similar efficacy and comparable bleeding risk with both agents.

Roe MT, Armstrong PW, Fox KAA, White HD et al Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012, 367:1297-309

TICAGRELOR

• Reversible P2Y12 receptor blocker that provides a rapid, consistent and more effective antiplatelet effect than clopidogrel.

• It was initially compared with clopidogrel in patients with ACS in the PLATO trial, results of which demonstrated improved efficacy outcomes (including reduced mortality) with similar rates of major bleeding.

Wallentin L, Becker RC, Budaj A,et al: Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009, 361:1045-57

• Pre-specified subgroup analysis from the PLATO trial in medically managed patients with ACS demonstrated similar results to the overall cohort with a reduction in mortality (6.1% vs. 8.2%; P = 0.01) and a slightly higher incidence of major bleeding (11.9% vs. 10.3%; P = 0.08) using ticagrelor compared to clopidogrel.

James SK, Storey RF, Khurmi Nset al: Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. Circulation 2012, 125:2914-21.

VORAPAXAR

• Vorapaxar is a oral PAR-1 antagonist that inhibits thrombin induced platelet activation,

• a mechanism that is entirely different from those of other available antiplatelet agents.

• Vorapaxar was tested as an adjunctive agent in patients with NSTE–ACS in the TRACER trial.

Leonardi S, Tricoci P,White HD, Armstrong PW et al: Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial. Eur Heart J 2013, 34:1723-31

• This study randomized 12,944 patients with NSTE–ACS to receive vorapaxar or placebo along with routine therapy.

• Over a median follow up period of over 500 days, there was no significant reduction in primary endpoint (death, myocardial infarction and stroke) but there was a substantial increase in major bleeding events (7.2%vs. 5.2%; P<0.001) and intracranial hemorrhage (1.1% vs. 0.2%; P<0.001) with vorapaxar when compared to placebo

ABCIXIMAB

• Intravenous glycoprotein (GpIIb/IIIa) inhibitors.• A meta-analysis on upstream abciximab (a GpIIb/IIIa

inhibitor) use in patients with NSTE–ACS (n = 46,374 patients) revealed only minor improvements in outcomes at the risk of increased bleeding .

• Current guidelines recommend use of this agent only in high-risk patients who have a high thrombus burden in primary PCI.

Tricoci P, Newby LK, Hasselblad V, et al: Upstreamuse of small-molecule glycoprotein iib/ iiia inhibitors in patients with non-ST-segment elevation acute coronary syndromes: a systematic overview of randomized clinical trials. Circ Cardiovasc Qual Outcomes 2011, 4:448-58.

• Even in patients with STEMI, there is a great deal of uncertainty about the preferred route of abciximab administration (intracoronary vs. intravenous).

• The AIDA STEMI randomized trial compared the two routes of abciximab in 2,065 patients presenting within 12 hours of STEMI.

• Intracoronary and intravenous abciximab resulted in a similar rate of the primary combined endpoint of death, reinfarction, or congestive heart failure at 90 days of follow up.

Thiele H, Wöhrle J, Hambrecht R, et al: Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. Lancet 2012, 379:923-31

• Statistically fewer patients in the intracoronary group had new congestive heart failure (2·4% vs. 4·1%; P = 0·04).

• The results confirmed that, although intracoronary abciximab resulted in a significant improvement in myocardial perfusion without any excess of major bleeding, there was no clear mortality benefit with this strategy.

Kubica J, Koziński M, Navarese EP, et al: Updated evidence on intracoronary abciximab in ST-elevation myocardial infarction: a systematic review and meta-analysis of randomized clinical trials. Cardiol J 2012, 19:230-42

REPERFUSION AT A PCI-CAPABLE HOSPITAL

5) ANTICOAGULANT THERAPY TO SUPPORT PRIMARY PCI AND RECENT ADVANCES

For patients with STEMI undergoing primary PCI, the following supportive anticoagulant regimens are recommended:

• UFH, with additional boluses administered as needed to maintain therapeutic activated clotting time levels,

• Bivalirudin with or without prior treatment with UFH.

I IIa IIb III

I IIa IIb III

It is reasonable to use bivalirudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist.

Fondaparinux should not be used as the sole anticoagulant to support primary PCI because of the risk of catheter thrombosis.

I IIa IIb III

I IIa IIb III

Harm

ADJUNCTIVE ANTITHROMBOTIC THERAPY TO SUPPORT

REPERFUSION WITH PRIMARY PCI

*The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily.

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 P2Y 12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty alone according to the recommendations listed for BMS. (LOE: C).

ADJUNCTIVE ANTITHROMBOTIC THERAPY TO SUPPORT REPERFUSION WITH PRIMARY PCI (CONT.)

ADJUNCTIVE ANTITHROMBOTIC THERAPY TO SUPPORT REPERFUSION WITH PRIMARY

PCI (CONT.)

UNFRACTIONATED HEPARIN VS. BIVALIRUDIN

• Previously published results 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.

O’Gara PT, Kushner FG, Ascheim DD et al.: 2013 ACCF/AHA guideline for the management of ST-elevationmyocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013, 61:e78-140

• The benefits of bivalirudin are mainly in its ability to reduce bleeding risk.

• Retrospective analysis from Sweden’s SCAAR database (41,537 consecutive NSTE–ACS patients none of whom received GP IIb/III inhibitors) revealed no benefits from using bivalirudin rather than heparin.

• Head to head trials comparing bivalirudin with unfractionated heparin (VALIDATE–SWEDEHEART, HEAT–PPCI) are currently underway.

Swedish registry questions superiority of bivalirudin over heparin in patients undergoing PCI for NSTE-ACS. [http://www.escardio.org/about/press/press-releases/pr-13/Pages/europcr-day1.aspx - registry].

RESIDUAL RISK AND USE OF ORAL ANTICOAGULANTS

• Patients with ACS remain at a significant risk of recurrent ischemic events after initial revascularization despite optimal medical therapy including DAPT and aggressive risk factor modification.

• 1 in 10 patients experiences a significant atheroembolic event (cardiac death, myocardial infarction or stroke) within a year of the first ACS episode.

Go AS, Mozaffarian D, Roger VL, et al.: Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 2013, 127:e6-e245

• This is felt to be secondary to a persistent thrombogenic state that extends well beyond the initial ACS event.

• New oral anticoagulants have emerged in the last decade with the potential to minimize residual risk.

RIVAROXABAN

• Rivaroxaban is a direct factor Xa inhibitor that ultimately leads to decreased generation of thrombin.

• Safety and efficacy of rivaroxaban in different doses (5–20 mg) was initially tested in a phase II dose finding trial (ATLAS ACS TIMI–46) that revealed a dose-dependent increase in the rate of bleeding and a reduction in ischemic events in patients with ACS.

Mega JL, Braunwald E, Mohanavelu S et al : Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009, 374:29-38

• Subsequently, a larger phase III trial (the ATLAS ACS TIMI–51) was launched that randomized over 15,000 patients with ACS to receive either rivaroxaban (2.5 or 5 mg twice daily) or placebo in addition to standard medical therapy.

Mega JL, Braunwald E,Wiviott SD, Bassand J et al: Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012, 366:9-19.

• Over a mean follow up of 13 months, there was a 16% reduction in primary efficacy endpoint (cardiac death, myocardial infarction or stroke) with RIVAROXABAN as compared to placebo.

• However, there was a threefold increase in the risk of major bleeding and intracranial hemorrhage. This risk was lower with a reduced dose (2.5 mg) with relatively maintained efficacy.

• Overall there was a 36% reduction in all causes of death with low dose RIVAROXABAN as compared to placebo, which largely derived from a reduction in sudden cardiac deaths. Results were similar in a prespecified subgroup analysis in patients with STEMI.

Mega JL, Braunwald E, Murphy SA et al: Rivaroxaban in patients stabilized after a ST-segment elevation myocardial infarction: results from the ATLAS ACS-2-TIMI-51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51). J Am Coll Cardiol 2013, 61:1853-9

• A 2.5 mg twice daily dose of RIVAROXABAN was recently approved for the same indication by the European Commission

• Although no new data for other new oral anticoagulants (DABIGATRAN, APIXABAN, BETRIXABAN, DAREXABAN) were presented last year.

http://press.healthcare. bayer.com/en/press/news-details-page.php/15050/2013-0292

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

Fibrinolytic therapy should be given to patients with STEMI and onset of ischemic symptoms within the previous 12 hours when it is anticipated that primary PCI cannot be performed within 120 minutes of FMC.

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.

I IIa IIb III

I IIa IIb III

Fibrinolytic therapy should not be administered to patients with ST depression.

I IIa IIb III

Harm

INDICATIONS FOR FIBRINOLYTIC THERAPY WHEN THERE IS A >120-

MINUTE DELAY FROM FMC TO PRIMARY PCI

REPERFUSION AT A NON–PCI CAPABLE HOSPITAL

2) ADJUNCTIVE ANTITHROMBOTIC THERAPY WITH FIBRINOLYSIS

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

• aspirin should be continued indefinitely and

In patients with STEMI who receive fibrinolytic therapy:

I IIa IIb III

• clopidogrel (75 mg daily) for at least 14 days

• and up to 1 year I IIa IIb III

I IIa IIb III

ADJUNCTIVE ANTIPLATELET THERAPY WITH FIBRINOLYSIS

It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy.

I IIa IIb III

REPERFUSION AT A NON–PCI-CAPABLE HOSPITAL

3) ADJUNCTIVE ANTICOAGULANT THERAPY WITH FIBRINOLYSIS

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.

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:

• 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

ADJUNCTIVE ANTITHROMBOTIC THERAPY TO SUPPORT REPERFUSION WITH FIBRINOLYTIC

THERAPY

DELAYED INVASIVE MANAGEMENT

CORONARY ANGIOGRAPHY IN PATIENTS WHO INITIALLY WERE MANAGED WITH

FIBRINOLYTIC THERAPY OR WHO DID NOT RECEIVE REPERFUSION

Cardiac catheterization and coronary angiography with intent to perform revascularization should be performed after STEMI in patients with any of the following:

a. Cardiogenic shock or acute severe HF that develops after initial presentation;

b. Intermediate- or high-risk findings on predischarge noninvasive ischemia testing; or

c. Myocardial ischemia that is spontaneous or provoked by minimal exertion during hospitalization.

I IIa IIb III

I IIa IIb III

I IIa IIb III

• Coronary angiography with intent to perform revascularization is reasonable for patients with evidence of failed reperfusion or re-occlusion after fibrinolytic therapy.

• Angiography can be performed as soon as logistically feasible.

• Coronary angiography is reasonable before hospital discharge in stable patients with STEMI after successful fibrinolytic therapy.

• Angiography can be performed as soon as logistically feasible, and ideally within 24 hours, but should not be performed within the first 2 to 3 hours after administration of fibrinolytic therapy.

I IIa IIb III

I IIa IIb III

INDICATIONS FOR CORONARY ANGIOGRAPHY IN PATIENTSWHO WERE MANAGED WITH FIBRINOLYTIC THERAPY OR WHO DID NOT RECEIVE REPERFUSION THERAPY

CORONARY ARTERY BYPASS GRAFT SURGERY

CABG IN PATIENTS WITH STEMI

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

The use of mechanical circulatory support is reasonable in patients with STEMI who are hemodynamically unstable and require urgent CABG.

Emergency CABG within 6 hours of symptom onset may be considered in patients with STEMI who do not have cardiogenic shock and are not candidates for PCI or fibrinolytic therapy.

I IIa IIb III

I IIa IIb III

Timing of Urgent CABG in Patients With STEMI in Relation to Use of Antiplatelet Agents

Aspirin should not be withheld 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

Abciximab should be discontinued at least 12 hours before urgent CABG.

Urgent off-pump CABG within 24 hours of clopidogrel or ticagrelor administration might be considered,

Urgent CABG within 5 days of clopidogrel or ticagrelor administration or within 7 days of prasugrel administration might be considered,

I IIa IIb III

I IIa IIb III

I IIa IIb III

ROUTINE MEDICAL THERAPIES

BETA BLOCKER

Oral ẞ blockers should be initiated in the first 24 hours in patients with STEMI who do not have any of the following:signs of HF, evidence of a low output state, increased risk for cardiogenic shock,* or other contraindications to use of oral beta blockers.

Beta blockers should be continued during and after hospitalization for all patients with STEMI and with no contraindications to their use.

I IIa IIb III

I IIa IIb III

Patients with initial contraindications to the use of beta blockers in the first 24 hours after STEMI should be re-evaluated to determine their subsequent eligibility.

It is reasonable to administer i.v beta blockers at the time of presentation to patients with STEMI and no contraindications to their use who are hypertensive or have ongoing ischemia.

I IIa IIb III

I IIa IIb III

Renin-Angiotensin-Aldosterone System Inhibitors

An ACE inhibitor should be administered within the first 24 hours to all patients with STEMI with anterior location, HF, or EF less than or equal to 0.40, unless contraindicated.

An ARB should be given to patients with STEMI who have indications for but are intolerant of ACE inhibitors.

I IIa IIb III

I IIa IIb III

An aldosterone antagonist should be given to patients with STEMI and no contraindications who are already receiving an ACE inhibitor and beta blocker and who have an EF less than or equal to 0.40 and either symptomatic HF or diabetes mellitus.

ACE inhibitors are reasonable for all patients with STEMI and no contraindications to their use.

I IIa IIb III

I IIa IIb III

Lipid Management

High-intensity statin therapy should be initiated or continued in all patients with STEMI and no contraindications to its use.

It is reasonable to obtain a fasting lipid profile in patients with STEMI, preferably within 24 hours of presentation.

I IIa IIb III

I IIa IIb III

OTHER NOVEL AGENTS

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

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

• 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.

• The TIME trial randomized 120 subjects with myocardial infarction and impaired ventricular function that underwent PCI to receive either autologous bone marrow cells or 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

• The patients were randomized to one of four groups: day 3 stem cell (after myocardial infarction); day 3 placebo; day 7 stem cell; day 7 placebo infusions.

• At 6 months follow up there were no differences in changes in cardiac function (ejection fraction) among any of the groups.

• Two trials—the ALLSTAR (allogenic cardiac stem cells) and BAMI (autologous bone marrow cells)—are currently enrolling patients and are underway.

HEMODYNAMIC SUPPORT IN

PCI

• Utilization of intra-aortic balloon pump (IABP) counterpulsation to support high-risk PCI.

• Even though there has been a lack of convincing evidence of improvement in outcomes, IABP support continues to be routinely utilized for high-risk patients with myocardial infarction and cardiogenic shock, and international guidelines had given it a Class I indication.

• To this effect, the IABP–SHOCK II randomized trial was launched to support the routine use of IABP in patients with cardiogenic shock.

• The investigators randomized 600 patients with acute myocardial infarction (AMI) and cardiogenic shock to IABP or no IABP support.

• Surprisingly, there were no differences in outcomes across the groups after a 30-day follow up period (no difference in mortality, length of hospital stay, renal function, and vasopressor use).

Thiele H, Zeymer U, Neumann F et al: Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med 2012, 367:1287-96

• The PRAMI trial was a non-blinded trial which randomized 465 patients presenting with STEMI to either primary PCI in an infarct-related artery alone or primary PCI and “preventive” PCI in a non infarct artery with >50% stenosis.

Wald DS, Morris JK, Wald NJ et al: Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med 2013, 369:1115-23

• There was a significant reduction in the primary endpoint, a composite of cardiac death, myocardial infarction and refractory angina in the preventive PCI group when followed over 2 years (9% vs. 23%; HR: 0.35).

• There was a trend towards a reduction in mortality although it was not statistically significant.

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