04. NSTE-ACS Management

Introduction

  • The key to the management of NSTE-ACS is to eliminate ischemia. This is achieved through medical therapy and revascularization when indicated.
  • The first step is to risk stratify patients using clinical judgment and evidence-based risk scores.
  • Next, all patients receive medical therapy and are considered for revascularization via an early invasive strategy or ischemia-guided strategy.
  • Interval reevaluation should be performed to evaluate for indications for escalation of level of care or emergency catheterization.
  • Finally, before discharge, patients should be started on evidence-based medical therapies, counseled on health behaviors, and scheduled for close follow-up.

Risk Stratification

  • Risk stratification is important both in terms of prognosis and in choosing an early invasive versus ischemia-guided strategy for catheterization. Higher risk patients tend to benefit from earlier revascularization.
  • Two commonly used risk scores are the TIMI Risk Score (below) and the GRACE Risk Score (https://www.mdcalc.com/grace-acs-risk-mortality-calculator).
    • Generally, patients with TIMI score 0 to 2 are considered low risk, 3 to 4 intermediate risk, and 5 to 7 high risk. Patients with GRACE score ≤108 are considered low risk, 109-140 are considered intermediate risk, and >140 are considered high risk.
  • Clinical consideration of risk is equally important, and can change management. This is discussed in more detail in “Revascularization” below.

TIMI Risk Score for NSTE-ACS

 

Age ≥ 65

1

≥3 CAD risk factors (hypertension, hypercholesterolemia, diabetes, family history of CAD, or current smoker)

1

Known CAD (≥50% stenosis)

1

ASA use in past 7 days

1

Severe angina (≥2 episodes in last 24 hours)

1

EKG with ST changes ≥0.5 mm

1

Positive cardiac biomarker

1

Medical Management

  • Medical management consists of antiplatelet therapy, anticoagulant therapy, anti-ischemic therapy, and statin therapy.
    • All patients should receive the following therapies unless specific contraindications exist.
  • Antiplatelet therapy:
    • All patients should receive dual antiplatelet therapy with aspirin and a P2y12 inhibitor.
    • Aspirin: 325 mg loading dose once, followed by 81 mg daily.
    • P2y12 inhibitors:
      • Either ticagrelor or clopidogrel are reasonable choices for upfront (prior to cath) P2y12 inhibition. It is important to administer these at the proper loading doses.
      • Ticagrelor 180 mg PO loading dose once, followed by 90 mg BID.
      • Clopidogrel 600 mg PO loading dose once, followed by 75 mg daily.
      • Prasugrel is not recommended upfront therapy.
    • Gp2b inhibitors:
      • Should be restricted to use in the catheterization lab.
  • Anticoagulant therapy:
    • All patients should receive an anticoagulant agent as part of therapy.
    • Unfractionated heparin:
      • Administered for 48 hours or until PCI is performed.
      • Dosing: bolus heparin IV 60 units/kg (max 4000 units) followed by heparin gtt 12 units/kg/hr (max 1000 units) adjusted per PTT to maintain therapeutic anticoagulation.
    • Enoxaparin:
      • Administered for duration of hospitalization up to eight days or until PCI is performed.
      • Dosing: 1 mg/kg SQ q12h.
      • For patients who are not going to catheterization, enoxaparin is the preferred agent given a mortality benefit over heparin.
    • Other options include fondaparinux (preferred if high bleeding risk, only for patients not going to the catheterization lab), bivalirudin (only for patients managed with an early invasive strategy and generally restricted to cath lab use), and argatroban (for patients with HIT).
  • Anti-ischemic therapy:
    • Patients should receive anti-ischemic therapy to both reduce myocardial oxygen demand and/or increase myocardial oxygen supply.
    • Nitrates:
      • Nitrates should be used for patients with ischemic chest pain.
        • These are contraindicated in patients who have recently taken a PDE5 inhibitor (within 24 hours for sildenafil/vardenafil or 48 hours for tadalafil).                       
        • Avoid nitroprusside as this may precipitate coronary steal.
      • Sublingual nitroglycerin 0.4mg q5min up to three doses.
      • If chest pain is unrelieved with sublingual nitroglycerin, IV nitroglycerin gtt is indicated as permitted by blood pressure. Administer 0-300 mcg/min with the intention of relieving chest pain.
    • Beta-blocker:
      • Initiate beta-blockers within 24 hours of presentation and ideally as soon as possible.
        • Contraindicated in patients who have signs of acute heart failure, evidence of low output state such as elevated lactate, are at increased risk of cardiogenic shock, bradycardia (i.e. HR <50) or who otherwise would have had contraindicated beta-blocker use.
        • Avoid use of IV beta-blockers.
        • Metoprolol tartrate 12.5 mg or 25 mg PO q6hr and uptitrate for heart rate goal in the 50s.
    • ACE inhibitor:
      • Captopril 6.25 mg PO three times daily and uptitrate for SBP goal 120-130.
      • Use cautiously in the first 24 hours in instances of hypotension or renal dysfunction. In particular, avoid IV ACE inhibitor.
    • Oxygen supplementation:
      • Start supplemental oxygen only if SpO2 <90%.
        • Avoid excessive oxygen supplementation (only target SpO2 >90%) as excess oxygen may increase infarct size.
  • Statin: should be started on a high intensity statin such as atorvastatin 80 mg PO daily as soon as possible.
  • Medications/therapies to avoid:
    • IV beta-blocker, IV ACE inhibitor, and nifedipine.
    • Morphine or other opioid analgesics as this has been associated with increased mortality.
    • Oxygen therapy for SpO2 >90.
    • NSAIDs as they compete with the effect of aspirin.
    • Steroids.
    • Hormone replacement therapy should be used cautiously.

Revascularization

  • There are two treatment pathways in terms of revascularization: early invasive strategy versus ischemia-guided strategy.
    • Candidates for early invasive strategy:
      • TIMI score ≥2.
      • Refractory angina.
      • Hemodynamically unstable, or with an electrically unstable arrhythmia.
      • Patients with rapid temporal changes in troponin, EKG change, LVEF <40%, or prior CABG/PCI.
    • Candidates for ischemia-guided strategy:
      • Low risk score: TIMI score 0-1 or GRACE <109.
      • Patient or clinician preference in the absence of high-risk features.
  • Early invasive strategy:
    • Patients undergoing early invasive strategy are further stratified into timing of their catheterization based on clinical signs and risk scores: immediate catheterization, early catheterization, or delayed catheterization.
    • Immediate catheterization (within 2 hours):
      • Patients with refractory or recurrent angina.
      • Patients with signs/symptoms of heart failure.
      • Patients with new or worsening mitral regurgitation.
      • Patients with hemodynamic instability.
      • Patients with sustained ventricular tachycardia or ventricular fibrillation.
    • Early catheterization (within 24 hours):
      • New ST segment depression.
      • GRACE score >140.
      • Temporal change in troponin.
    • Delayed catheterization (within 72 hours):
      • Renal insufficiency (GFR <60).
      • LVEF <40%.
      • Early post-infarction angina.
      • History of PCI within the past six months.
      • Prior CABG.
      • GRACE score 109-140.
      • TIMI score ≥2.
  • Ischemia-guided strategy:
    • Patients undergoing ischemia-guided strategy are started on medical therapy and receive risk stratification using noninvasive testing.
    • Patients should be started on evidence-based medical therapy.
    • Patients should receive noninvasive testing prior to hospital discharge to detect severe ischemia occurring at low stress threshold.
      • TTE.
      • Noninvasive stress test, such as treadmill exercise test, stress testing with imaging modality, or pharmacologic stress test.
    • If patient’s initial angina cannot be managed medically, they have recurrent ischemia or their stress test returns positive, they should undergo coronary angiography +/- PCI.

Interval Re-evaluation

  • Patients should receive frequent re-evaluation when admitted for NSTE-ACS.
  • Angina refractory to medical therapy, hemodynamic instability, and uncontrolled arrhythmias are indications for CCU level of care.
  • Importantly, by definition the distinction between STE-ACS and NSTE-ACS are electrocardiographic. However, there are patients who meet criteria for emergent catheterization regardless of features on EKG, as discussed above. A minority of patients initially classified as NSTE-ACS without the need for immediate catheterization may later meet these criteria. Patients with NSTE-ACS should be frequently re-evaluated to see if they meet criteria for immediate catheterization.

Pre-Discharge Care

  • Prior to discharge, patients should have their LVEF assessed via TTE.
  • Additionally, evidence-based medical therapy regimens should be optimized:
    • Antiplatelet therapy: dual antiplatelet therapy with aspirin and a P2y12 inhibitor for 12 months regardless if they received PCI in order to reduce risk of a subsequent CV event.
    • Anti-ischemic therapy:
      • Beta-blocker: should be continued in all patients with a diagnosis of NSTE-ACS.
        • Patients with reduced systolic function should receive metoprolol XL, carvedilol or bisoprolol
      • ACE inhibitor: should be transitioned to long-acting formulation and continued indefinitely.
        • ARBs should be used if intolerant to ACE inhibitors.
    • Nitrates: should be discharged with sublingual nitroglycerin 0.3 to 0.4mg q5min PRN up to three doses.
      • Patients with ongoing angina at time of discharge need further evaluation prior to discharge.
  • Statin: should be continued on high intensity statin.
  • Mineralocorticoid receptor antagonist: start in all patients who are on therapeutic doses of ACE inhibitors and beta-blockers and have LVEF less than 40% with diabetes.
    • Contraindicated in patients with significant renal dysfunction or hyperkalemia.
  • Patients should receive counseling on smoking cessation, diet, and exercise.
  • Patients should be counseled to avoid NSAIDs.
  • Patients should receive primary care follow-up, cardiology follow-up, and referral to cardiac rehabilitation.
    • Cardiac rehabilitation confers a mortality benefit and thus attempts to refer prior to discharge should be strongly considered.

References

Levine, Glenn N., et al. "2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart ...." Circulation 134.10 (2016): e123-e155.