0

No perfusion; no antegrade flow beyond point of occlusion

1

Penetration without perfusion; failure of contrast medium to move out of the area of occlusion

2

Partial perfusion; passage of contrast medium through obstruction but at a slow rate of clearance

3

Complete perfusion; prompt antegrade flow distal to the obstruction and adequate clearance of contrast medium

Markers

• Age ≥75 years (3 pts), 65–74 years (2 pts), < 65 years (0 pts)

• Diabetes mellitus, hypertension, or angina (1 pt)

• Systolic blood pressure < 100 mmHg (3 pts)

• Heart rate > 100/min (2 pts)

• Killip Class II–IV (2 pts)

• Weight < 67 kg (1 pt)

• Anterior ST-segment elevation or LBBB (1 pt)

• Time to treatment > 4 h (1 pt)

Numbers of markers designate risk of all cause 30-day mortality

• 0: 0.8 %

• 1: 1.6 %

• 2: 2.2 %

• 3: 4.4 %

• 4: 7.3 %

• 5: 12.4 %

• 6: 16.1 %

• 7: 23.4 %

• 8: 26.8 %

• 9–14: 35.9 %

Antiplatelet pharmacotherapy for an initial invasive approach (angiography +/− stent)

• Patients with UA/NSTEMI at medium or high risk who an invasive strategy is selected should receive dual antiplatelet therapy on presentation (note: prasugrel should only be given at the time of angiography/PCI)

• Platelet function testing to determine platelet inhibitory response on P2Y₁₂ receptor inhibitor therapy may be considered. Role of genotyping in the clinical management of patients has not been established

• Aspirin (if no evidence of allergy)

   ○ 162–325 mg (non-enteric coated) chew and swallow immediately, followed by 81 mg enterally daily (indefinitely); inquire about prehospital administration of aspirin

      ■ If history of aspirin-induced bleeding or bleeding risk factors present, may use a lower initial dose (i.e., 81 mg daily)

      ■ A loading dose followed by a maintenance dose of clopidogrel, prasugrel, or ticagrelor in patients who are not able to take aspirin; dual P2Y₁₂ receptor inhibitor therapy is not recommended

   ○ Dual therapy with a P2Y₁₂ receptor inhibitor is recommended with one of the following regimens (either clopidogrel, prasugrel, or ticagrelor [note: the ACCF/AHA does not rank these agents in order of preference]):

• Clopidogrel

   ○ 600 mg enterally before or at the time of PCI followed by 75 mg daily for at least 12 months; a shorter duration should be considered if increased bleeding risk

      ■ 75 mg twice daily for 6 days, then 75 mg daily may be considered in patients not at high risk for bleeding

      ■ Review medication profile for potential drug–drug interactions

   ○ In patients whom an initial invasive approach is planned and if bivalrudin is selected as the anticoagulant during PCI:

      ■ 300 mg enterally for one dose at least 6 h earlier than PCI, followed by 75 mg daily for 12 months in addition to aspirin pharmacotherapy

       □ Do not use combination therapy in patients at high risk of bleeding or if the need for urgent CABG cannot be excluded

• Prasugrel

   ○ 60 mg enterally at the time of PCI (no later than 1 h after PCI) followed by 10 mg daily for at least 12 months; a shorter duration should be considered if increased bleeding risk

      ■ Prasugrel should not be administered routinely in patients with UA/NSTEMI before angiography

   ○ Potentially harmful in patients with a prior history of stroke and/or transient ischemic attacks

   ○ Patients <60 kg may be at increased risk for bleeding with a 10 mg daily regimen; consider lowering the dose to 5 mg daily

   ○ Generally not recommended in patients ≥75 years except in high-risk situations (e.g., diabetes or prior myocardial infarction); if utilized consider lowering the dose to 5 mg daily

• Ticagrelor

   ○ 180 mg enterally before or at the time of PCI followed by 90 mg twice daily for at least 12 months; a shorter duration should be considered if increased bleeding risk

   ○ The recommended concomitant aspirin dose to be used is 81 mg daily

   ○ Should be avoided in patients with a prior history of intracranial hemorrhage

• Glycoprotein IIb/IIIa inhibitors (given during angiography)

   ○ PCI dosing not provided

   ○ The use of upstream (at presentation and before angiography) glycoprotein IIb/IIIa inhibitors may be considered in high-risk patients (e.g., elevated troponin levels, diabetes, or significant ST-segment depression). Administered, in addition to aspirin and a P2Y₁₂ receptor inhibitor; may be administered just before PCI

   ○ Either eptifibatide or tirofiban can be administered for initial early treatment in addition to aspirin and clopidogrel or ticagrelor plus an anticoagulant before diagnostic angiography

      ■ Either low molecular weight heparin (LMWH), fondaparinux or heparin in intermediate to high-risk patients in whom an invasive management strategy is planned (see Table 2.3 for risk assessment)

      ■ Eptifibatide can be continued for 12–18 h after angiography

      ■ Tirofiban can be continued up to 18 h after angiography

   ○ If bivalirudin is chosen as the anticoagulant, can omit administration of an IV glycoprotein IIb/IIIa inhibitor

   ○ Glycoprotein IIb/IIIa inhibitors are not recommended in patients with a low risk for ischemic events (i.e., TIMI risk score ≤ 2) or who are at high risk for bleeding

   ○ Abciximab is not indicated in patients in whom PCI is not planned

Anticoagulant pharmacotherapy for an initial invasive approach

• One anticoagulant should be added to antiplatelet therapy

• Bivaliruin (given during angiography)

   ○ Peri-PCI dosing not provided

   ○ Can continue at a dose of 0.25 mg/kg/h up to 72 h if given before diagnostic angiography

• Unfractionated heparin (given during angiography)

   ○ Peri-PCI dosing not provided

   ○ May be combination with antiplatelet pharmacotherapy for at least 48 h

   ○ After PCI dosing: weight-based dosing to achieve an activated partial thromboplastin time (aPTT) between 50 and 70 s (note: some institutions titrate heparin to anti-Factor Xa levels)

      ■ 60–70 units/kg IV bolus (4,000 units maximum), followed by 12–15 units/kg/h continuous IV infusion (1,000 units/h maximum)

   ○ Nomogram for adjusting the heparin infusion

aPTT (s)

Rebolus

Stop infusion

Change infusion

<35

80 units/kg

–

↑ by 4 units/kg/h

35–49

40 units/kg

–

↑ by 2 units/kg/h

50–70

–

–

–

71–90

–

–

↓ by 2 units/kg/h

>90

–

1 h

↓ by 3 units/kg/h

      ■ If patient is obese, utilize an adjusted body weight for heparin dosing

       □ Adjusted body weight = ideal body weight + 0.3 (actual body weight – ideal body weight)

      ■ Check aPTT every 6 h until stable then every 12–24 h

   ○ Use beyond 48 h is indicated in patients with refractory or recurrent angina or a large infarction

• Low molecular weight heparins

   ○ Enoxaparin may be preferred over unfractionated heparin in intermediate to high-risk patients (see Table 2.3 for risk assessment)

   ○ Enoxaparin

      ■ 1 mg/kg SQ every 12 h for 2–8 days

      ■ Adjust dose if CrCl < 30 mL/min. Consider avoiding if CrCl < 15 mL/min

   ○ Fondaparinux

      ■ 2.5 mg SQ q24h for up to 8 days

      ■ Contraindicated if CrCl < 30 mL/min

      ■ Per guidelines, if used during PCI, it must be coadministered with another anticoagulant with anti-Factor IIa activity

• Warfarin with concomitant aspirin and P2Y₁₂ receptor inhibitor therapy may be considered if clinically indicated but is associated with an increased risk of bleeding

   ○ May be used if patients are intolerant to P2Y₁₂ receptor inhibitor therapy

   ○ Goal INR = 2–2.5 with concomitant aspirin therapy or dual antiplatelet therapy

   ○ Goal INR = 2.5–3.5 without antiplatelet therapy

Anti-ischemic pharmacotherapy

• β-adrenergic blockers

   ○ Early intravenous β-adrenergic blockers are to be used with extreme caution, strictly avoided in patients with evidence or significant risk of developing hemodynamic instability, heart failure or bradyarrythmias

   ○ Oral β-adrenergic blockers should be given in the first 24 h in the absence of contraindications

   ○ Avoid early if cocaine-induced acute coronary syndrome (relative contraindication)

      ■ Metoprolol

       □ 5 mg IV every 5 min for three total doses (if hypertensive, hyperdynamic, or tachydysrhythmia present and risk factors for cardiogenic shock are not present [e.g., age > 70 years, SBP < 120 mmHg, HR > 110/min]). Usually start with oral β-adrenergic blocker therapy within 24 h

       □ Step-down to or initiate 25–50 mg enterally q6–12h

      ■ Propranolol

       □ 1 mg slow intravenous push (IVP), repeated every 5 min; not to exceed a total of 5 mg (if hypertensive, hyperdynamic, or tachydysrhythmia present and risk factors for cardiogenic shock are not present [as above])

       □ An alternative dosing regimen may be 0.1 mg/kg in three divided doses every 2–3 min. Do not exceed a rate of 1 mg/min

• Contraindications to β-adrenergic blockers

   ○ Bradycardia (heart rate < 60/min), systolic blood pressure < 100 mmHg, severe left ventricular dysfunction with pulmonary edema, second-degree or third-degree heart block, PR-interval >0.24 s, evidence of hypoperfusion, or active asthma

   ○ Avoid β-adrenergic blockers with intrinsic sympathomimetic activity (e.g., acebutolol, pindolol)

• Nitroglycerin

   ○ Sublingual 0.4 mg tablets every 5 min × three doses on presentation (inquire about prehospital administration of nitroglycerin) in the presence of ongoing ischemia. Initiate intravenous pharmacotherapy if chest pain persists

   ○ Start continuous IV infusion at 5–10 mcg/min and titrate using 5–10 mcg/min increments until symptoms resolve or systolic blood pressure (SBP) < 90 mmHg or mean arterial pressure (MAP) falls by ≥ 30 mmHg from baseline. Usual maximum dose = 200 mcg/min; indicated in the first 48 h

   ○ Avoid in patients with:

      ■ Right ventricular infarction

      ■ If presenting SBP is < 90 mmHg or ≥ 30 mmHg below baseline MAP

      ■ Presence of profound bradycardia or tachycardia

      ■ Recent use (within 24 h of sildenafil or vardenafil or within 48 h of tadalafil) of a phosphodiesterase-5 inhibitor for erectile dysfunction (or pulmonary hypertension)

   ○ Use beyond 48 h is indicated in patients with persistent angina or pulmonary congestion

   ○ Dilates large coronary arteries and collateral vessels

   ○ Some intravenous preparations contain significant amounts of ethanol

Adjuvant pharmacotherapy

• Angiotensin converting enzyme inhibitors (ACE-I)—(oral therapy within 24 h after presentation)

   ○ Greatest benefit in patients with left ventricular dysfunction (ejection fraction [EF] < 40 %), anterior wall infarction, or pulmonary congestion. Use without these conditions is still warranted

   ○ Angiotensin receptor blockers if allergic or intolerant to ACE-I (data with valsartan and candesartan)

   ○ Start with low doses and increase as tolerated

• Statins

   ○ Commence therapy within 24–96 h after admission (i.e., atorvastatin 80 mg enterally daily)

   ○ If patient is on a statin before admission, continue therapy during admission to avoid rebound phenomenon

• Morphine

   ○ 2–5 mg IV over 5 min every 5–30 min as needed

• Oxygen therapy

   ○ Administer to patients with an SaO₂ < 90 % or respiratory distress

   ○ Little justification for use beyond the first 2–6 h in the uncomplicated patient

• Sodium nitroprusside (dilates only large coronary arteries and not collateral vessels)

   ○ May cause coronary steal. Avoid general utilization in patients with acute coronary syndromes. If therapy is indicated, use in combination with nitroglycerin, as this agent dilates large coronary arteries and collateral vessels

Fibrinolytic pharmacotherapy (in the absence of contraindications)

• Indicated for patients with ischemic symptoms of ≤12 h in duration in whom, primary PCI cannot be performed within 120 min of first medical contact, and 12-lead electrocardiogram (ECG) evidence of:

   ○ ST-elevation >0.1 mV in at least two contiguous precordial leads or at least two adjacent limb leads

   ○ New (or presumed new) left-bundle-branch block

   ○ A true posterior wall infarction

      ■ May manifest as tall R waves in the right precordial leads and ST-segment depression in leads V₁–V₄

   ○ Some beneficial evidence exists to support administration times of up to 24 h after symptom onset in patients with continuous ischemic symptoms

• Alteplase, reteplase, or tenecteplase preferred over streptokinase in:

   ○ Patients with symptom duration ≤ 6 h

   ○ Anterior wall infarction (large area of injury)

• Administration within 30 min of arrival into the healthcare system recommended

• Exclude contraindications (see Table 2.7)

Agents for IV administration

• Alteplase (tPA)

   ○ 15 mg IV bolus followed by 0.75 mg/kg continuous IV infusion (not to exceed 50 mg) over 30 min, followed by 0.5 mg/kg continuous IV infusion (not to exceed 35 mg) over 1 h; total dose not to exceed 100 mg.

• Reteplase (rPA)

   ○ 10 units IV push over 2 min followed 30 min later with another 10 units IV push over 2 min (administer a normal saline flush with each dose)

• Tenecteplase (TNKase)—single dose IV push over 5 s

   ○ <60 kg—30 mg

   ○ 60–69.9 kg—35 mg

   ○ 70–79.9 kg—40 mg

   ○ 80–89.9 kg—45 mg

   ○ ≥90 kg—50 mg

• Streptokinase

   ○ 1.5 million units continuous IV infusion over 30–60 min using a ≥ 0.5 μm in-line filter

   ○ Monitor for any signs of an allergic reaction

   ○ Antibodies remain for at least 3–6 months after administration

Evidence of improvement

• Relief of presenting signs and symptoms

• Sustained hemodynamic and electrical stability

• A reduction of at least 50 % of the ST-segment elevation on follow-up ECG obtained 60–90 min after fibrinolytic therapy

Adjuvant antiplatelet pharmacotherapy after fibrinolytic therapy

• Aspirin 162–325 mg X 1 dose followed by 81–325 mg daily indefinitely (81 mg is the preferred maintenance dose)

• Clopidogrel

   ○ ≤75 years: 300 mg loading dose followed by 75 mg daily for at least 14 days and up to 1 year

   ○ >75 years: no loading dose, give 75 mg followed by 75 mg daily for at least 14 days and up to 1 year

Adjuvant anticoagulant pharmacotherapy after fibrinolytic therapy

• Unfractionated heparin (given with fibrinolytics)

   ○ Should receive for a minimum of 48 h and preferable the duration of initial hospitalization (up to 8 days or until potential revascularization)

   ○ As adjunct therapy to the use of alteplase, reteplase, or tenecteplase

      ■ 60 units/kg IV bolus (4,000 units maximum), followed by 12 units/kg/h continuous IV infusion (1,000 units/h maximum)

   ○ For patients receiving streptokinase

      ■ Recommended if patient is at high risk for systemic thromboembolism (anterior wall infarction, heart failure, left ventricular thrombus, atrial fibrillation, previous embolism)

   ○ Weight-based dosing to achieve an activated partial thromboplastin time (aPTT) between 50 and 70 s (note: some institutions titrate heparin to anti-Factor Xa levels)

      ■  60–70 units/kg IV bolus (4,000 units maximum), followed by 12–15 units/kg/h continuous IV infusion (1,000 units/h maximum)

   ○ Nomogram for adjusting the heparin infusion

aPTT (s)

Rebolus

Stop infusion

Change infusion

<35

80 units/kg

–

↑ by 4 units/kg/h

35–49

40 units/kg

–

↑ by 2 units/kg/h

50–70

–

–

–

71–90

–

–

↓ by 2 units/kg/h

>90

–

1 h

↓ by 3 units/kg/h

      ■ If patient is obese, utilize an adjusted body weight for heparin dosing

       □ Adjusted body weight = ideal body weight + 0.3 (actual body weight – ideal body weight)

      ■ Check aPTT every 6 h until stable then every 12–24 h

      ■ For patients receiving concomitant fibrinolytic pharmacotherapy, check an aPTT 3 h after heparin initiation

   ○ Use beyond 48 h is indicated in patients with refractory or recurrent angina or a large infarction

• Enoxaparin for up to 8 days or until revascularization

   ○ If < 75 years: 30 mg IV bolus followed in 15 min by 1 mg/kg SQ q12h (note: maximum of 100 mg for the first two doses)

      ■ Adjust maintenance dose to q24h if CrCl < 30 mL/min; consider avoiding if CrCl < 15 mL/min

   ○ If ≥ 75 years: no bolus; 0.75 mg/kg SQ q12h (note: maximum of 75 mg for the first two doses)

      ■ Adjust maintenance dose to q24h if CrCl < 30 mL/min; consider avoiding if CrCl < 15 mL/min

• Fondaparinux for up to 8 days or until revascularization

   ○ 2.5 mg IV, then 2.5 mg SQ daily starting on the following day

   ○ Contraindicated of CrCl < 30 mL/min

Adjuvant antithrombotic therapy after PCI performed after fibrinolytic therapy

• Aspirin

   ○ Count any loading dose administered with fibrinolytic therapy (before PCI) followed by 81–325 mg daily indefinitely (81 mg is the preferred maintenance dose)

• Clopidogrel

   ○ 300 mg loading dose if PCI performed ≤ 24 h after fibrinolytic therapy (if not loaded previously)

   ○ 600 mg loading dose if PCI performed > 24 h after fibrinolytic therapy (if not loaded previously)

   ○ Maintenance dose is 75 mg daily for at least 30 days and up to 1 year with a bare-metal stent or at least 1 year with a drug-eluting stent

• Prasugrel

   ○ May be used in place of clopidogrel in a patient who has not received a previous loading dose of clopidogrel at the time of fibrinolytic administration

   ○ 60 mg loading dose if PCI performed > 24 h after a fibrin-specific agent (e.g., tenecteplase, reteplase, alteplase)

   ○ 60 mg loading dose if PCI performed > 48 h after a non-fibrin-specific agent (e.g., streptokinase)

   ○ Maintenance dose is 10 mg daily for at least 30 days and up to 1 year with a bare-metal stent or at least 1 year with a drug-eluting stent

   ○ Should not be administered in patients with a history of prior stroke or transient ischemic attack

• Heparin

   ○ Continue through PCI and maintain therapeutic activated clotting time of 250–300 s (HemoTec device) or 300–350 s (Hemochron device) taking into account if a GP IIb/IIIa receptor antagonist is utilized

• Enoxaparin

   ○ Additional dosing is not needed if the last administered dose was within 8 h; administer 0.3 mg/kg IV if the last administered dose was between 8 and 12 h earlier

• Fondaparinux is not recommended as the sole anticoagulant in PCI; a concomitant agent with activity against clotting Factor IIa should be administered

Adjuvant antiplatelet pharmacotherapy after PCI performed (only)