Management of Acute Coronary Syndrome

Table of Contents

Table of Contents

Published October 2023

Author(s): Samantha Coffer Thielen, MD1; Sarah Slaven, MD2; Joseph Burke, MD3
Executive editor(s): Yilin Zhang, MD4; Brandon Fainstad, MD5

1Resident, Department of Medicine, University of Colorado

2Fellow, Department of Medicine, Division of Cardiology, University of Colorado

3Assistant Professor, Department of Medicine, Division of Cardiology, University of Colorado

4Assisstant Professor, Department of Medicine, University of Washington – Valley Medical Center

5Associate Professor, Department of Medicine, University of Colorado


  1. Select appropriate early medical interventions to address oxygenation, pain, antiplatelet and anticoagulation therapy in patients presenting with acute coronary syndrome (ACS).
  2. Determine timing of revascularization in STEMI versus NSTEMI with and without high-risk features.
  3. Select appropriate medical therapies for ACS to initiate prior to discharge based on ACS-type, revascularization methods and patient comorbidities. 

Teaching Instructions

Plan to spend at least 30-60 minutes preparing for this talk by reviewing the teaching script and clicking through the graphic animations on the Interactive Board to become familiar with the flow and content of the talk. Print out copies of the Learner’s Handout so learners may take notes as you expand on management and apply it through practice cases. Begin with reviewing the objectives for the session. All clickable elements are indicated by a cursor icon. 

The anticipated time to deliver this talk is about 20-25 min without cases and 35-45 min with cases. 

The talk can be presented in 2 ways:

  1. Project the “Interactive Board” OR
  2. Reproduce your own drawing of the presentation on a whiteboard

Objective 1: Select appropriate early medical interventions to address oxygenation, pain, antiplatelet and anticoagulation therapy in patients presenting with acute coronary syndrome (ACS) (Early Tx)

The early management of patients presenting with ACS is the same regardless of ACS-type (STEMI, NSTEMI, or unstable angina). Initial therapies should be aimed at addressing stabilizing vital signs (e.g., addressing hypoxia and hypotension), pain control, and antiplatelet and anticoagulant management. 

Click on each of the letters on the timeline to reveal the medications below. 







  • SpO2 <90%
  • Respiratory distress
  • Other high risk features of hypoxemia


Supplemental O2 in patients with STEMI without hypoxemia may be harmful (AVOID trial, 2015)

Anticoagulation and Antiplatelet Therapy






  • All patients with chest pain
  • 325 mg once (chewable or PR)
  • Active major bleeding
  • Hypersensitivity




  • NSTEMI undergoing early invasive PCI <48h
  • Major active bleeding
  • HIT
  • Hypersensitivity to pork products

Anticoagulant of choice for use peri-procedure because of quick on/off


Medical management of NSTEMI (no plan for revascularization)

  • Active major bleeding
  • HIT
  • Hypersensitivity to pork products
  • ESRD or significant renal dysfunction (CrCl <30) 

Reduces death, MI, recurrent angina at 14 days (versus heparin) in medical management of NSTEMI (ESSENCE trial, 1997)


Pain control






  • 1st line anti-anginal
  • Sublingual tablet 0.4 mg q5 min x 3
  • R-sided (inferior) MI
  • Hypotension (SBP <90)
  • Severe aortic stenosis
  • Hypertrophic cardiomyopathy
  • Marked tachy/bradycardia
  • PDE5 inhibitor within prior 24 h

If persistent angina after 3 doses, can escalate to IV nitroglycerin drip


  • 2nd line anti-anginal
  • Initiate within 24 h for both STEMI and NSTEMI
  • Cardiogenic shock
  • Bradycardia (HR <45), 2nd or 3rd degree AV block, sick sinus syndrome
  • Hypotension (SBP <100)
  • Periodically determine eligibility to initiate beta-blocker if there are initial contraindications
  • Start at low doses and titrate up as tolerated
  • Improves mortality


  • 2nd line anti-anginal
  • Used when maximized on nitrates and beta-blockers
  • Hypotension
  • Bradycardia
  • Lethargy, respiratory depression
  • Use of MAOIs within the last 14 d
  • Use with caution is CrCl <30

Increases mortality and may mask refractory angina

GP IIb/IIIa inhibitor (eptifibatide)

  • 2nd line anti-anginal
  • Considered in high-risk scenarios such as high thrombus burden, under direction of interventional cardiologist
  • Major active bleeding
  • History of hemorrhagic CVA or CVA within 30 d
  • Major surgery within 6 wks
  • Severe hypertension (BP >200/110)
  • ESRD on HD
  • Cautious use if INR >2 or platelet >100k
  • Not routinely used in ACS given limited evidence of benefit and increased risk of bleeding
  • Need for GP IIa/IIIb inhibitor for refractory angina should prompt discussion of urgent PCI
  • Often given after PCI if large thrombus burden identified (Coronary Revasc Guidelines 2021, class IIb recommendation)

Objective 2: Determine timing of revascularization in STEMI versus NSTEMI with and without high risk features (PCI)

STEMIPatients presenting with STEMI should undergo immediate revascularization.

  • At PCI capable hospitals, the goal is to undergo PCI within 90 minutes (assuming symptom onset is <12 hours). Door to balloon time begins when the patient comes through the doors of the hospital until balloon angioplasty of culprit vessel. Time is myocardium! The goal of quick blood restoration is to prevent permanent myocardial damage in the territory of the culprit vessel which could result in reduced ejection fraction and HF.
  • At non-PCI capable hospitals, the goal then shifts to transferring patients to a PCI-capable hospital.
    • Transfer should occur to PCI capable hospital if this can occur <120 min.
    • If there is no PCI capable hospital within 120 min, then fibrinolytics should be given within 90 min. Multiple RCTs and meta-analyses demonstrate PCI is superior to fibrinolytics. Fibrinolytics do not achieve perfusion in 35% of patients and are also associated with higher rates of death, MI, CVA, and major bleeding, therefore this strategy should only be used only if transfer to PCI capable hospital door to balloon time is >120 minutes.
      • Delayed angiography with possible PCI (3-24 hours) should be pursued after fibrinolytic therapy since fibrinolytics often does not achieve reperfusion, especially if recurrent symptoms or ECG changes.
    • There are some situations where PCI is not possible due to anatomy, in these cases emergent CABG can be considered as a primary reperfusion strategy if there is ongoing ischemia and large myocardial territory at risk.
    • If symptom onset was >12 hours, PCI is typically still pursued unless there is a totally occluded infarct and there are no ongoing symptoms of ischemia.

NSTEMI: Two main approaches exist for treating non-ST elevation MI (NSTEMI). Invasive strategy vs. ischemia guided strategy. The invasive strategy includes patients undergoing diagnostic angiography with intent to revascularize prior to hospital discharge. The alternative, ischemia guided strategy, treats medically and only recommends invasive evaluation with angiography for those who fail medical therapy (refractory angina), have objective evidence of ischemia (dynamic EKG changes, perfusion defect) or have clinical indicators of high prognostic risk. Routine use of the invasive strategy is associated with improved outcomes (lower composite death, MI or refractory angina at 4-6 months). However, ischemia guided strategy can be considered as an approach in very low risk patients per AHA/ACC guidelines.

Click on “risk stratification”. The timing of revascularization first requires risk stratification. Some very high-risk features clinical features require urgent revascularization. The GRACE and TIMI scores can be used to help determine risk of death within 90 days (GRACE) or all-cause mortality at 14 days (TIMI) based on individual risk factors and presenting features. Click on “GRACE” and “TIMI” to open each respective calculator. You may choose to review the clinical features and comorbidities included in each risk score.

  • Immediate PCI -urgent/immediate revascularization within 2 h is indicated for patients with very high-risk features such as:
    • Cardiogenic shock [SHOCK 1999]
    • Hemodynamic instability (MR or VSD)
    • Angina despite max medical therapy – take chest pain seriously, treat as able with nitroglycerin, but once maximized therapy, must revascularize. Ongoing pain = ongoing ischemia.
    • Unstable arrhythmia (VT/Vfib)
  • High risk – early invasive revascularization <24 hours is indicated for high risk patients such as:
    • GRACE >140 or elevated TIMI scores 6-7
    • Age >75
    • Elevated cardiac biomarkers
    • New ST depression
  • Moderate to low risk – delayed invasive revascularization at 25-72 hours (preceded by initial medical management) can be considered in GRACE 109-140 or TIMI 3-5. In this group a delayed strategy (25-72 hours rather than <24 hours) showed no difference in mortality.
  • Very low risk – ischemia-guided strategy can be considered for very low risk patients per patient or clinician preference in the absence of high risk features.
    • Very low risk features: GRACE <109 or TIMI 0 or 1
    • Medical management, only pursue invasive diagnostic angiography if:
      • Failed medical therapy (refractory angina
      • Objective evidence of ischemia (dynamic ECG changes, perfusion defect
      • Clinical indicators of high prognostic risk


Revascularization should not be delayed for patients who require emergent or urgent PCI for initiation of medical management.

Objective 3: Select appropriate medical therapies for ACS to initiate prior to discharge based on ACS-type, revascularization methods and patient comorbidities (Late Tx)

Management of early therapies





Continued as needed



81 mg daily should be continued as part of dual antiplatelet therapy (DAPT) post-PCI or in patients with CAD

If triple therapy (anticoagulation + DAPT) if needed, some patients may be able to stop aspirin after a period of time to decrease risk of bleeding


·      If PCI → often stopped immediately after successful revascularization, though may be continued if large thrombus burden visualized during coronary angiography

·      If no PCI in NSTEMI → continue anticoagulation for 48 h



·      Initiated within 24 h (if not contraindications)

·      Continued through discharge



Pain control

·      PRN nitroglycerin can be continued at discharge

·      GP IIa/IIIb may be initiated or continued post-PCI in patients with high thrombosis burden for a period of time



Additional therapies






  • High intensity statin (atorvastatin, rosuvastatin)
  • Initiated within 24 h
  • Active liver disease or unexplained persistent LFT abnormalities
  • Pregnancy or breast feeding
  • Caution with history of statin induced myopathy
  • Some experts recommend early initiation of statin prior to PCI for plaque stabilization
  • Reduces LDL but also has acute anti-inflammatory effects (MIRACL, 2001)

P2Y12 inhibitor

  • STEMI and NSTEMI post-PCI with stent (typically x 1 y)
  • NSTEMI – medical management as part of DAPT
  • 5 days prior to CABG due to increased bleeding risk
  • Ticagrelor (history of ICH, severe hepatic impairment)
  • Prasugrel – prior TIA/CVA, weight <60 kg, age >70, severe hepatic impairment
  • PO clopidogrel should not be given with omeprazole
  • Ticagrelor is recommended in STEMI. It is often preferred in all ACS given superiority over clopidogrel (PLATO 2009)


  • STEMI – all patients
  • NSTEMI – initiate prior to discharge in patients with LVEF <40% and/or HTN, DM, or stable CKD
  • Hypotension
  • AKI, hyperkalemia
  • CKD with CrCl < 10
  • History angioedema
  • Breastfeeding, pregnancy
  • 30 day mortality benefit


STEMI and NSTEMI – initiate prior to hospital discharge if LVEF <40%, HF, or diabetes

  • Hyperkalemia
  • Renal dysfunction (Cr >2.5 in M, >2 in F)
  • Pregnancy
  • 30 day mortality benefit
  • Initiate if already tolerating therapeutic doses of beta-blocker and ACE/ARB

Take Home Points

  1. Patients presenting with STEMI to PCI-capable hospital should undergo emergent revascularization within 90 minutes. If non-PCI capable hospital transfer to PCI capable hospital if PCI is possible within <120 minutes. If not, use fibrinolytics if no contraindications, then transfer for delayed angiography.
  2. Patients presenting with NSTEMI should be risk stratified into very high risk, high risk, moderate to low, or very low risk categories using TIMI/GRACE scores or clinical features. Patients with very high risk and high risk features should undergo immediate and early revascularization, respectively.
  3. In general aspirin, anticoagulation and pain management (including beta-blocker) should occur immediately if there are no contraindications, but not to delay emergent revascularization in patients with STEMI and very high risk NSTEMI. Statin and P2Y12 inhibitor should be added within 24 hours. ACE inhibitor/ARB and MRA should be added prior to discharge (after revascularization) if indicated.


Yilin Zhang


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