Pharmacotherapy of ACS – STEMI

Acute Management

Pathophysiology

· Complete occlusion of the coronary artery

Incidence

Diagnosis

· Angina

· EKG Changes

· ST elevation in the absence of LVH or LBBB (ESC/ACCF/AHA/World Heart Federation Task Force)

· ST elevation at the J point in at least 2 contiguous leads of > 2mm in men or > 1.5mm in women in leads V2-3 or > 1mm in other contiguous chest leads or limb leads

· ST depression in > 2 precordial leads (V1-4) transmural posterior injury

· Multilead ST depression with coexistent ST elevation in lead aVR LM or pLAD occlusion

· Majority will evolve to Q-waves

· New (or presumed new) LBBB has been considered a STEMI equivalent

· Need an old EKG to confirm, as LBBB may be old or new

· New LBBB occurs infrequently and will interfere with ST elevation analysis, and should not be considered diagnostic of acute MI in isolation

· Baseline EKG abnormalities (paced rhythm, LVH, Brugada syndrome) may obscure interpretation

· Rarely, hyperacute T wave changes may be observed in very early phases of STEMI (before ST elevation)

· Troponin rise

Goals of Therapy

· Reperfusion of the occluded artery as soon as possible (STEMI = 35-40% mortality (sudden cardiac death))

· Minimize myocardial damage and total ischemic time (time from onset of symptoms to initiation of reperfusion therapy) Goal door to balloon time of 90 minutes; door to needle time of 30 minutes)

· Establish and maintain patency of the infarct-related artery

· Alleviate the signs and symptoms

· Prevent short-term and long-term re-occlusion, re-infarction, re-hospitalization, stent thrombosis

· Prevent mortality (70% of CAD-death = out of hospital SCD)

· Minimize ADRs, cost ; enhance QoL, compliance

Reperfusion therapies: Fibrinolytic, Primary PCI, Medical management, CABG

When to choose which strategy…

Fibrinolytic

Primary PCI

Facilitated PCI

(Full/half dose Lytic +/- GPIIbIIIa + PCI)

· Early presentation (< 2-3h from symptom presentation)

· Presenting <12h of symptoms

· Use if presenting to a facility without primary PCI, unable to obtain vascular access

· Cannot receive PCI < 120 mins (e.g. prolonged transport)

· No absolute contraindications to fibrinolytic

· High risk STEMI (cardiogenic shock, Killip class > 3) regardless of time delay from MI onset

· If the facility has PCI capabilities with surgical backup

· PCI can be performed < 120 minutes

· Late presentation (>3-4h)

· Patient is at ↑ bleeding risk (ICH) or have relative or absolute cinx to lytic

· Diagnosis of STEMI is in doubt

· If patients are high risk

· PCI not immediately available < 90 minutes

· Bleeding risk is low (young age, no poorly controlled HTN, normal weight)

· Despite potential advantages, clinical trials have not demonstrated benefit in reducing infarct size or improving outcomes (ASSENT-4PCI: trial was terminated early because of increased in-hospital mortality)

Fibrinolytics

· Indication: In those who have no contraindications, for STEMI with symptoms in the previous 12h and in whom EKG demonstrates ST-segment elevation greater than 0.1mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads, or new LBBB (greatest benefit in trials seen in anterior MIs or LBBB)

· ~60% of patients achieve TIMI 3 flow at 60 minutes (streptokinase is not used because only 30% of patients achieve TIMI 3 flow at 60mins)

· 9 trials from the Fibrinolytic Therapy Trials Collaborative Group found reduction in 35d mortality of lytic vs. controls in those who arrived

· < 6h of symptoms: 30 in 1000 ; 7-12h of symptoms: 20 in 1000

· Evidence

· TIMI: Phase 1 trial, evolving MI, alteplase >> streptokinase in achieving coronary reperfusion

· GUSTO I: RCT, <6h CP and STEMI, TPA + IV UFH > SK + IV UFH for 30d mortality

· SK better for > 75y and inferior MI (less hemorrhagic stroke)

· TPA better for age <75 and anterior MI (reduced mortality, increased risk of hemorrhagic stroke)

· GUSTO III: RCT, OL, reteplase = tpa for 30d mortality

· ASSENT 2: RCT, in pts presenting <6h with CP and STEMI, TNK 0.5mg/kg x 1 = TPA for 30d mortality

· If receiving lytic, should undergo anticoagulation tx for minimum of 48h If do not use, vessel will re-occlude

· Pre-hospital lytic: meta of 6 trials showed that prehosp lytic > inhosp lytic for all-cause mortality (OR 0.83), time to lytic was reduced with prehosp lytic (104 vs. 162 mins) AHA guidelines say you may initiate lytic out of hospital if physician present or EKG is being transmitted

· If lytic fails, do PCI (“Rescue PCI”)

· Urgent transfer to PCI

· Lytic failure: ST elevation less than 50% reduced after 90 minutes following initiation of lytic therapy in the lead showing the worst initial elevation

· REACT: Rescue PCI is superior to conservative therapy or repeat fibrinolysis for MACE at 6m

· If lytic was successful, still do PCI (“Pharmacoinvasive strategy”)

· Transfer the patient within 3-24 hours (ideally 2-3 hours); but do not perform PCI within first 2-3h of lytic

· TRANSFER AMI: STEMI < 12h, all received TNK, ASA, UFH/Enox, Clop was encouraged, early PCI (<6h) > standard tx (PCI < 2 weeks) for MACE

· Risk factors for post-lytic ICH: female, age > 75y, < 67kg, UFH dose

Primary PCI

· Primary PCI produces higher rates of infarct artery patency, TIMI 3 flow, access site bleeding, but lower rates of recurrent ischemia, reinfarction, emergency repeat revascularization, ICH and death

· 95% of patients achieve TIMI 3 flow at 60 minutes (vs 60% for lytic)

· Meta of 23 RCTs that compared primary PCI to lytic found PCI to be superior for short-term and long-term adverse outcomes, including death (if can get door-to-balloon time <90mins)

· DANAMI-2: <12h CP, < 3h PCI site, PCI+transfer > lytic for recurrent MI; no difference in death/stroke

· If >2h door to balloon time, PCI was associated with increased mortality rates (as per multivariate analyses)

· The effectiveness of both lytic and PCI diminishes with the passage of time, but ability of PCI to produce a patient infarct-related artery is much less time dependent PCI is preferred for patients who arrive at the hospital late after onset of symptoms (>3h)

· Early initiation of lytic (2-3h) may produce better outcomes than PCI

· If patient presents to a non-PCI hospital and the time to primary PCI exceeds 120 mins, the survival benefit of primary PCI over lytic is negated (Circulation. 2011;124:2512–21)

· Early PCI better for those with cardiogenic shock SHOCK trial

· Observational data from the National Registry of MI suggest that PCI is superior to lytic for patients with HF or Killip class > 2

Acute Management: mnemonic = MONA

· Morphine, Oxygen, Nitrates, ASA (Oxygen, ASA, Nitrates, Morphine)

Antiplatelets

Antiplatelets for Medically-Managed STEMI Reduce platelet aggregation and activation

· ASA 160-320mg STAT, then 81mg PO daily indefinitely (ISIS-2)

· P2Y12 Inhibitor STAT

· Duration of therapy: 1 year (guidelines)

· Clopidogrel 300mg STAT then 75mg PO daily (or 75mg stat then 75mg daily for those >75y)

· COMMIT CCS 2: N=45,852, <24h STEMI/LBBB/↓ST on ASA/50% lytic, clopidogrel 75mg PO daily x 4 weeks or until discharge > PB for death/MI/CVA (no difference in bleeding)

· CLARITY TIMI 28: N=3491, <12h STEMI/LBBB+ASA/UFH/lytic, clopidogrel 300mg then 75mg daily > PB for TIMI0-1/death/MI (outcome was angiographically driven; no difference in bleeding rates)

· Ticagrelor 180mg STAT then 90mg BID

· PLATO: <24h ACS, ticagrelor > clopidogrel 300/75 for CV death/MI/CVA; ticagrelor had mortality benefit and increased dyspnea

· GP IIb/IIIa inhibitor do not use in medically-managed STEMI

· MOA: interrupt final common pathway of fibrinogen-mediated cross-linkage of platelets, works on activated platelets

· In STEMI, only abciximab studied in combo with lytic (half-dose reteplase); increased TIMI-3 flow at 60-90mins, but no mortality benefit and increased ICH bleeding (FINESSE)

· ASSENT 3: <6h CP, STEMI/LBBB

TNK (full dose) +

UFHx48h

TNK (full dose) +

Enox 30mg IV,

1mg/kg q12hx7d

TNK (1/2 dose) +

Abciximab +

IV UFH

p-value

(abc/enox vs. UFH)

Composite

(30d mortality, in-hosp reinfarction/ischemia)

15.4%

11.4%

11.1%

p=0.0001

Death

6%

5.4%

6.6%

p=0.25

Re-infarction

4.2%

2.7%

2.2%

p=0.0009

Recurrent ischemia

6.5%

4.6%

3.2%

p<0.0001

In-hospital ICH

0.9%

0.9%

0.9%

p=0.98

Major bleed

2.2%

3%

4.3%

p=0.0005

· GUSTO V: <6h CP and STEMI, rpa+abciximab+UFH = rpa+UFH for mortality/hemorrhagic stroke, but had increased rates of major bleeding and ICH in >75y

· If bleeding on GPIIbIIIa, have to give platelet infusion

Antiplatelets in PCI

· ASA 160-320mg STAT, then 81mg PO daily indefinitely (ISIS-2, CURRENT-OASIS 7)

· P2Y12 Inhibitor STAT

· Duration of therapy: 1 year (guideline), but commonly we do 1 month for BMS and 1 year for DES

· Clopidogrel 300-600mg STAT then 75mg PO daily (duration varies for DES vs BMS), give load even if on clopidogrel PTA

· PCI-CLARITY: Clopidogrel 300mg load then 75mg + lytic, PCI was performed 2-8d later, clopidogrel > PB for CV death/MI/CVA at 30d, no difference in rates of bleeding

· CREDO: ACS/selective PCI on ASA+clopidogrel, 300mg LD > no load for death/MI/CVA at 1y (89% >1 stent)

· ARYMADA-2: clopidogrel 4-8h before PCI, 600mg LD > 300mg for 30d death/MI/TVR

· CURRENT OASIS 7: 68% PCI, 29%STEMI, clop 600mg, 150mg x 6 days, then 75mg = 300mg CV death/MI/stroke at 30d (for PCI subgroup, 600mg > 300mg), but slight ↑ in major bleeding (2.5% vs. 2%)

· Prasugrel 60mg STAT then 10mg PO daily

· TRITON-TIMI 38: ACS and scheduled PCI, prasugrel > clopdogrel 300/75 for CV death/MI/CVA; no benefit in hx TIA/stroke, age > 75, wt < 60

· Ticagrelor 180mg STAT then 90mg BID

· PLATO: <24h ACS, ticagrelor > clopidogrel 300/75 for CV death/MI/CVA; ticagrelor had mortality benefit and increased dyspnea

· GP IIb/IIIa inhibitor (in STEMI, use ASA/clopdogrel witth UFH/bivalrudin instead)

· A lot of the evidence for GPIIbIIIa inhibitors were established before the era of dual oral antiplatelet therapy and were largely placebo controlled (in the 1990s)

· Evidence: ADMIRAL, CADILLAC, EPILOG, CAPTURE, EPISTENT, RESTORE, TARGET, ESPIRIT

· There is a paucity of data for assessment for GPIIbIIIa in the era of ASA+clopidogrel

· Not used routinely, but may use at time of PCI if large thrombus noted, didn’t receive clopidogrel load, or if there may be a delay to PCI, especially if ongoing chest pain despite MONA, ASA, clopidogrel, anticoagulation

· Works on activated platelets, ?better for later presentation

· All 3 GPIIbIIIa considered equal: two meta-analyses of RCTs showed that abciximab = tirofiban/eptifibatide

· BRAVE 3: PCI within 24h, 600mg clopidogrel, abciximab = PB for death/MI/CVA/ Δ in infarct size/major bleeding

· ON-TIME 2: RCT, UFH/Clopidogrel/ASA/tirofiban then primary PCI, tirofiban > PB for improved ST-segment resolution before and 1h after PCI; no difference in TIMI flow and no difference in bleeding (major or minor)

· MULTISTRATEGY: STEMI + primary PCI with ASA/clopidogrel/UFH, tirofiban = abciximab for 50% ST resolution at 90 minutes after primary PCI; abciximab had increased thrombocytopenia (moderate to severe)

· Faciliated PCI

· ASSENT-4: <6h STEMI + primary PCI 1-3h TNK + PCI > Primary PCI for death/HF/shock, but increased rate of in-hospital ICH (no mortality benefit)

· FINESSE: pre-primary PCI tx with half-dose lytic + abciximab vs. abciximab at time of PCI had no benefit (any outcome) but increased bleeding

Anticoagulation Prevent deposition of fibrin strands into the clot

· STEMI patients should receive anticoagulation for at least 48h and up until hospital discharge or 8 days (regardless of lytic/PCI).

· UFH 60U/kg bolus (max 4000U) then 12U/kg/h (max 1000U/h) for 48h after lytic with target aPTT 50-70s (1.5-2x ULN) (ASSENT-1 showed ↓ICH with 4000U bolus vs. 5000U)

· Mainstay of anticoagulation in STEMI for >40y; most studied anticoagulant with primary PCI

· Use smaller, weight-adjusted doses vs. doses stratified by weight lower rates of major bleeding and refractory ischemia, with similar rates of 30d mortality, recurrent ischemia and ICH

· APTT 50-70 had lowest 30d rates of mortality/stroke/bleeding/refractory ischemia

· If planning to give anticoagulation for >48h, use something other than UFH (increased incidence of HIT)

· Recent meta-analysis showed that UFH use during hospitalization did not prevent reinfarction or death (Circulation. 2005 Dec 20:112(25):3855-67)

· UFH may be better than LMWH in those >75y who received lytic

· ASSENT III-PLUS: N=1639, STEMI + tenecteplase + ASA, enox x 7d = UFH 48h for death/in-hospital re-infarction or in-hospital refractory ischemia at 30d. Enox increased ICH (2.2% vs. 0.97%), driven by >75y

· LMWH > UFH/PB

· LMWH (enoxaparin) is superior to UFH for MACE, and the benefits outweigh the increased risk of bleeding noted

· If patient is >150kg, use UFH as there was a study showing increased adverse outcomes if enox was used in this population

· Some centres cap the dose of enox at 100mg/dose (from NSTEMI trials)

· Recent meta analysis showed that LMWH for 4-8d > PB for death and reinfarction

· CLARITY TIMI 28: STEMI, LMWH > UFH closed infarct-related artery/death/MI before angiography/death/recurrent MI with similar bleeding rates

· ASSENT 3: TNK + enox > TNK + UFH

· EXTRACT-TIMI 25: RCT, N=20,506, < 6h STEMI + 100% TNK + ASA, enox 30mg IV then 1mg/kg SC BID x 7d (duration of hospitalization) > UFH 60U/kg IV bolus then 16U/kg/hr x 48h for death/MI at 30d (symptom to needle time was 3.2h) Enox ↑ major bleeding (2.1% vs. 1.4%, p<0.001)

· CREATE: STEMI, reviparin (not available in US) vs. PB reduced MACE but small increase risk of bleeding

· Fonda > UFH (medical management of STEMI, use if hx HIT)

· OASIS-6: < 12h STEMI, 45% lytic/30%PCI, fonda 2.5mg S.C. daily x 8d > UFH for death/reinfarction at 30d

· Fonda had tendency of decreased bleeding complications

· Fonda not beneficial in primary PCI, but may use up until rescue PCI then change to UFH

· Fonda vs. UFH had increased catheter thrombosis – do not use in primary PCI!

· If fonda is used, have to use UFH or bivalrudin in addition to mitigate this increased risk

· Avoid in CrCL<30, although no increase in bleeding in this population in OASIS 6

· If bleed on fonda, give Factor VIIa

· Note, VTE tx dose of fonda is 5-10mg S.C. daily, but this dose was no more effective than 2.5mg S.C. daily in ACS (no dose response curve)

· If going for PCI (regardless of UFH use before), may use bivalrudin 0.75mg/kg IV bolus then 1.75mg/kg/hr (reduce maintenance dose to 1mg/kg/h if CrCl<30mL/min)

· HORIZONS-AMI: N=3602, STEMI + primary PCI, bival > UFH+GPIIbIIIa for 30d death/MI/ischemic target vessel revascularization/stroke/major bleeding (driven by reduction in major bleeding); risk of acute stent thrombosis was higher in 24h, but not at 30d and 1y

RAAS Inhibitors

· ACEI: Greatest benefit in the first 5d .: give < 24h of MI in those with anterior STEMI, pulmonary congestion, EF < 40%

· SAVE (acute MI < 3-16d, EF<40%): captopril 50mg TID x 42m [CCS-1 (<36h NSTEMI/STEMI): Captopril 12.5mg TID x 4wks (NSS)]

· CONSENSUS II (<24h MI): Enalapril 2.5mg IV x 1 then 20mg BID x 6m (NSS< study terminated early due to increased death in enalapril - ?IV route the cause?)

· AIRE (MI 3-10d, HF): Ramipril 5mg BID x 15m

· GISSI 3 (<24h MI): Lisinopril 10mg daily x 6wks

· TRACE (MI 3-7d, EF<35%): Trandolapril 4mg daily (PEACE did not show difference, no LV dysfunction)

· Only use ARB if patient has been intolerant to ACEI in the past (OPTIMAAL [losartan vs. captopril], VALIANT [valsartan vs. captopril])

· May add aldosterone blocker if patient already on ACEI + BB and have EF < 40%, HF or DM2

BB Decreases myocardial contractility and HR, reduces myocardial O2 demand

· Evidence: reduces recurrent ischemia and reinfarction among patients with concomitant lytic therapy

· Should be initiated < 24h of hospitalization unless: signs of HF, evidence of low output state, increased risk for cardiogenic shock, heart block, active asthma, reactive airway disease

· Caution in using IV beta-blockers increases the risk of cardiogenic shock (may use if tachyarrhythmias or HTN)

· COMMIT/CCS Metoprolol 5mg IV x 3 then 200mg PO daily < 24h of MI

· Increased risk of cardiogenic shock by 30% (especially on day 0 and 1)

· Decreased reinfarction and ventricular fibrillation episodes

· COMMIT CCS 2 <12h STEMI/LBBB/STdep/50% lytic, metoprolol 5mg IV x 3 then 50mg PO q6h x 48h then 200mg SR daily x 4 weeks > PB for recurrent MI and VF, but increased cardiogenic shock/HF/hypotension ; no benefit for composite outcome

· ISIS1: < 12h MI: atenolol 5-10mg IV then 100mg x 7d > PB for 7d mortality

· MIAMI: < 24h MI, metoprolol 5mg IV q2mins x 3 then 50mg PO q6h x 48h vs PB

· No difference in 15d mortality; although retrospective analysis showed benefit of metoprolol in high risk patients

· Metoprolol group had less VF and anti-anginal effects

· Duration of therapy: has not been address in the STEMI guidelines, but secondary prevention guidelines recommend 3 years

· CCBs

· May use if BB are ineffective or contraindicated for relief of ongoing ischemia or control of rapid ventricular response in the absence of HF, LV dysfunction, or AV block

· Verapamil decreases risk of mortality in those with MI not in HF

· Diltiazem 60mg QID reduced cardiac events at 2y in a subgroup of patients without pulmonary congestion (MD PIT); in the overall group, there was no mortality benefit vs. PB

· Do not use immediate release nifedipine contraindicated in STEMI; amlodipine has not been studied

Chest pain management

· Nitrates (vasodilator in LV failure, decreases preload, reduces myocardial O2 demand, enhances myocardial O2 delivery by dilating large coronary arteries and improving collateral flow to ischemic areas)

· GISSI-3 and ISIS-4 found no mortality benefit with nitrates

· NTG 0.4mg SL 1-2 sprays q5min x 3 prn if no relief, go to NTG patch or IV infusion

· NTG IV infusion: 10 - 20 mcg/min, ↑ by 5 - 10 mcg/min q3-5 mins until the desired hemodynamic or clinical response

· NTG patch 0.2-0.8mg/h

· Do not use nitrates in: RV infarcts, concomitant use of phosphodiesterase inhibitors (e.g. sildenafil), aortic stenosis

· Morphine (decrease pain, decreases sympathetic drive, vasodilator, may decrease preload, decrease anxiety)

· 2.5-5mg IV q5mins prn if nitrates ineffective

· Use fentanyl instead if patient very hemodynamically unstable

· Do not use NSAIDs and COX-2 inhibitors: substudy analysis of EXTRACT-TIMI 25 demonstrated increased risk of death, reinfarction, heart failure, or shock in patients who were taking NSAIDs < 7 days of enrollment

Statin

· Evidence: reduces risk of CV death, recurrent MI, stroke, need for coronary revascularization

· Also stabilizes coronary plaques, pleiotropic effects

· Beneficial in those with low-normal LDL levels

Acute STEMI

· Use high dose atorvastatin

Prepared by Erica Wang Pharm.D. | Cardiac Services | Kelowna General Hospital | Interior Health Authority

Updated 16 July 2013

· 80mg PO daily

· PROVE-IT: <10d ACS or post-PCI, atorva 80 > prava 40 for death/MI/stroke/revascularization/CVA

· A tiered strategy (simvastatin 40mg daily x 1 month, then 80mg PO daily) did not reduce CV events (A to Z trial)

Warfarin

· WARIS-2: <75y, hospitalized for MI, 50% received lytic

Warfarin (INR 2.8-4.2)

ASA 160

Warfarin (INR 2-2.5) + ASA 75

Composite (death, MI, stroke at 4y)

16.7%

20%

15%

Death

7.8%

7.6%

7.8%

MI

7%

9%

5.7%

Stroke

1.3%

2.6%

1.4%

Major bleeding

0.68%/yr

0.17%/yr

0.57%/yr

· Warfarin+ASA > ASA for reducing composite, but no difference in mortality and increased bleeding

-evidence for actue LFEV dysfunction (WASH, WATCH and another one) is lack

Beneficial in actue MI, not in chronic HF; no evidence right now of acute HF and warfarin

Smoking Cessation

· Smoking cessation reduces subsequent CV mortality by 50%, all-cause mortality by 40%

· RCTs demonstrate that counseling smokers in hospital after acute MI increases cessation rates if initial contact is in hospital, then followed by repeat contacts, usually by telephone for > 3 months after discharge

· Similarly, the rates of smoking cessation are greater among patients who receive discharge recommendations for cardiac rehab

Complications after STEMI

Cardiogenic Shock

· Caused by extensive LV infarction or mechanical complications or RV infarction

· Most cases occur within 24h

· 15% occur at time of presentation and 85% develop during hospitalization

· Should do emergency revascularization with PCI or CABG irrespective of delay from MI onset

· May even PCI noninfarct arteries

· Administer lytic in those who are not suitable PCI or CABG candidates

· IABP may be helpful, especially in those who are not stable despite medical therapy

· Do not use dopamine

Severe HF

· LV myocardium may be ischemic, stunned, hibernating, infarcted

· Ischemic (functional) MR may coexist, progress and may require surgical intervention

· Indication to proceed with PCI if not previously performed

RV Infarction

· 1/3 of patients with interior STEMI may have an RV infarct

· Generally due to proximal occlusion of RCA

· Clinical diagnosis: inferior MI, hypotension, clear lungs, elevated JVP

· Treatment: maintain RV preload, reduce RV afterload

Mechanical Complications

· Most occur within 24h, remainder occur within first week (bimodal, temporal distribution)

· MR

· 2 mechanisms: papillary muscle rupture, or post-infarct LV remodeling with displacement of papillary muscles, leaflet tethering and annular dilatation

· Acute rupture often affects the posteromedial muscles more than anterolateral muscle because of its singular blood supply

· MV replacement rather than repair is generally required in this setting

· Even though emergency MV replacement is associated with high mortality rate (20%)

· Ischemic (functional) MR: treatment focused on timely reperfusion, diuretics, and afterload reduction

· Will improve with aggressive medical management, PCI or both

· MV repair generally indicated and preferred in many cases

· Ventricular Septal Rupture

· Diagnosis: loud systolic murmur, HF, shock

· Occurs most often within 24h after STEMI + lytic

· Emergency surgical repair is necessary, even in hemodynamically stable patients (because rupture site can expand)

· LV Free Wall Rupture

· Diagnosis: recurrent CP and ST/T wave changes with rapid hemodynamic collapse, EMD, death

· Observed frequently in patients with first MI, anterior infarct, elderly, women, HTN during STEMI, lack of angina prior to MI, no collateral blood flow, Q waves on ECG, use of CS/NSAIDs, lytic >14h after symptoms

· Mortality = 60%

· LV Aneurysm

· <5% of STEMI, occurs in those with anterior infarction

· Incidence has reduced with increasing use of primary PCI

Electrical Complications

· Ventricular Arrhythmias

· Common early after STEMI

· Those receiving PCI vs lytic had lower incidence of VT/VF (5.7% vs 10%)

· 90% occur within 48h of presentation

· Mortality is 2x higher in those with early VT/VF (pre-PCI) and 5x higher in those with late VT/VF (after PCI) compared to those without VT/VF

· Early administration of BB can reduce the incidence of VT/VF

· PVCs and NSVT not associated with hemodynamic compromise that occur after reperfusion do not increase risk of SCD and do not require therapy peri-STEMI

· ICDs

· Ventricular arrhythmias that occur > 48h after STEMI are usually associated with LV dysfx and poor prognosis

· If no reversible cause, late in-hospital sustained VT/VF is an indication for ICD therapy

· AF/SVTs

· Common post STEMI dur to excess sympathetic stimulation, atrial stretch due to LV/RV pressure overload, atrial infarction, [ericarditis, electrolyte abnormalities, hypoxia, lung disease

· AF most common: occurs in 8-22% of STEMI, higher rates in elderly, HF, HTN

· In hospital incidence: 9% (associated with shock, HF, stroke, 90d mortality)

· Bradycardias/AV Block/Intraventricular Conduction Defects

· Sinus bradycardia is common early after STEMI, especially if inferior infarct

· Mechanism: increased vagal tone

· Usually self-limited and generally requires no treatment

· Treat with atropine or temporary pacing if needed

· Development of AV block of intraventricular conduction delays is associated with extent of infarction

· Incidence of complete heart block: 3.7% in inferior/posterior MI and 1% in anterior/lateral MI

· First degree AV block does not require treatment

· Magnesium

· Early studies in STEMI showed that mg reduced mortality, but later studies showed no benefit

· MAGIC: Mg 2g IV x 1 = PB for 30d mortality

· Only use IV magnesium in those with documented magnesium deficits and those with TdP

Pericarditis

· Incidence has decreased with use of aggressive reperfusion

· Diagnosis: CP after STEMI (pleuritic or positional), radiates to trapezius ridge, associated with pericardial rub, recurrent/worsening ST elevation without early T wave inversion may be present

· Must distinguish from re-infaction and acute stent thrombosis

· Pericarditis is not absolute contraindication to anticoagulation, but caution due to potential for hemorrhagic conversion

· Anticoagulation should be discontinued in presence of significant or enlarging pericardial effusion (>1cm)

· Treatment

· ASA

· Acetaminophen, colchicine, narcotics may be used if ASA is not effective

· Avoid CS and NSAIDs

· Asymptomatic pericardial effusions are common after STEMI

· If effusion > 1cm in width, need to exclude free wall rupture

· If tamponade is present, free wall rupture, hemorrhagic conversion, aortic dissection should be considered

· If pain persistent > 1 week and accompanied by malaise, fever, increased inflammatory biomarkers, consider Dressler syndrome

Thromboembolic Events

· Anticoagulation is reasonable in those with LV mural thrombus (2013 AHA STEMI: LOE C)

· Duration: 3 months

· Anticoagulation may be considered in those with STEMI and anterior apical akinesis or dyskinesis (2013 AHA STEMI: LOE C)

· Target lower INR 2-2.5

· No anticoagulation trial included primary PCI or DAPT

· HIT

· 1-5% of patients receiving heparin will develop HIT

· 25-50% of these will develop thrombotic complications

· At risk of HIT in those receiving heparin for > 96h (CATCH registry)

· Associated with increased risk of death, MI, HF

Bleeding Complications

· Bleeding in STEMI is independently associated with recurrent MI, stroke, death, increase LOS, increased cost

· Risk of death increases as function of severity of bleeding, independent of success/failure of reperfusion

· HR for death within 30d = 1.6 to 10.6 (mild to severe bleeding)

· Likely related to patient comorbidities, discontinuation of antiplatelet/anticoagulant, blood transfusions

· Most bleeding is procedure related

· Overall incidence of major bleeding in STEMI: 3.8%

· Those who bled were more likely to die in hospital (20.9% vs 5.6%)

· Avoid transfusions unless Hgb <80g/L, minimize the number of units

· ICH

· Risk for ICH: older age, female, low body weight (<70kg female, <80kg male) hx CVA, HTN on presentation (with graded increase beginning at >160-170mmHg SBP)

· Once ICH is recognized, stop all antiplatelets and anticoagulants

· Vascular access site bleeding

· Most common type of bleeding post-STEMI

· Femoral access site bleeding risk: female, advanced age, renal insufficiency, anemia, IABP, use of GP IIb/IIIa inhibitors, LMWH within 48h

· Radial access may decrease complications and should be considered whenever feasible

· Does not reduce major bleeding, but reduces major vascular cmoplications

· Suspect retroperitoneal bleeding if: intraprocedural/postprocedural hypotension, bradycardia/tachycardia, high vascular puncture site, unexplained decrease in Hgb

AKI

· Try to minimize CIN by decreasing contrast volume and ensure optimal hydration

Hyperglycemia

· U-shaped relationship between glucose levels and death in STEMI/ACS

· Target BG 7-10, and not lower

· DIGAMI: acute MI, DM, BG>11, IV insulin x 24h then SC insulin QID x 3 months (target BG 7-10) > usual care for mortality at 1 and 3.4y

· DIGAMI-2: acute MI, DM, BG>11, IV insulin then SC insulin (BG 5-7) = IV insulin then SC insulin (BG 7-10) = usual care for all cause mortality (underpowered? Trend towards ↑ mortality in tight BG group 23% vs. 21% vs 18%)

· NICE-SUGAR: in medical and surgical ICU patients, tight BG control vs modest control increased mortality (primarily from CV causes) and hypoglycemic episodes

· GIK

· Do not use; CREATE-ECLA: < 12h STEMI/LBBB, GIK infusion x 24h = usual care for 30d mortality