What is the workup and treatment plan for a patient with acute coronary syndrome (ACS) and non-ST elevation myocardial infarction (NSTEMI) in the inpatient setting?

Acute Coronary Syndrome and NSTEMI: Inpatient Workup and Treatment

Initial Diagnostic Workup

Upon presentation, obtain a 12-lead ECG within 10 minutes of first medical contact and draw blood immediately for cardiac biomarkers (high-sensitivity troponin T or I), CK-MB, creatinine, hemoglobin, and leukocyte count. 1

ECG Findings

• Look for transient ST-segment depression, T-wave inversion, flat T waves, pseudo-normalization of T waves, or the ECG may be normal 1
• Record additional leads (V3R, V4R, V7-V9) if persisting chest pain to rule out posterior or right ventricular involvement 1
• Continuous ST-segment monitoring for at least 24 hours in a monitored unit 2

Cardiac Biomarker Strategy

• Use the ESC 0h/1h or 0h/2h algorithm with high-sensitivity troponin for rapid rule-in or rule-out 1
• Diagnosis requires troponin elevation above the 99th percentile upper reference limit with either rise or fall pattern, plus at least one of: symptoms of ischemia, new ischemic ECG changes, pathological Q waves, imaging evidence of new wall motion abnormality, or intracoronary thrombus 1
• Repeat troponin at 6-12 hours if initial values are borderline or clinical suspicion remains high 1

Additional Workup

• Measure left ventricular ejection fraction (LVEF) via echocardiography 2
• Calculate GRACE or TIMI risk score for risk stratification 2
• Assess renal function (creatinine clearance) to guide anticoagulant dosing 1

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Immediate Medical Management

Anti-Ischemic Therapy

Administer sublingual or IV nitrates immediately for ongoing ischemic symptoms unless contraindicated (systolic BP <90 mmHg, severe bradycardia, right ventricular infarction, or recent phosphodiesterase inhibitor use within 24-48 hours). 1, 2

• Start IV nitrates for uncontrolled hypertension or signs of heart failure 1
• Initiate beta-blocker therapy early unless contraindicated by overt heart failure, and continue chronic beta-blocker therapy 1, 2
• Administer supplemental oxygen only if arterial oxygen saturation is <90% 2

Antiplatelet Therapy

Immediately administer aspirin 162-325 mg loading dose (non-enteric coated), followed by 75-100 mg daily maintenance dose indefinitely. 1, 2

Add a potent P2Y12 inhibitor on top of aspirin—ticagrelor is the preferred agent (180 mg loading dose, then 90 mg twice daily) irrespective of planned treatment strategy. 1, 2

Alternative P2Y12 inhibitors:

• Prasugrel (60 mg loading dose, then 10 mg daily) is reasonable for patients undergoing early invasive strategy, but contraindicated in patients with prior stroke/TIA 1, 3
• Clopidogrel (300-600 mg loading dose, then 75 mg daily) only when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated 1, 4
• Avoid routine pre-treatment with P2Y12 inhibitors if coronary anatomy is unknown and early invasive management is planned 1

Do not use GP IIb/IIIa inhibitors (eptifibatide, tirofiban) routinely before coronary anatomy is known. 1

Anticoagulation Therapy

Initiate parenteral anticoagulation immediately for all NSTEMI patients in addition to antiplatelet therapy, selecting based on ischemic and bleeding risk. 1

Preferred options:

• Enoxaparin: 1 mg/kg subcutaneous every 12 hours (reduce to 1 mg/kg once daily if CrCl <30 mL/min), continued until PCI or hospital discharge 1
• Fondaparinux: 2.5 mg subcutaneous daily, continued until PCI or hospital discharge 1
• UFH: 60 IU/kg IV bolus (max 4000 IU), then 12 IU/kg/hour infusion (max 1000 IU/h), adjusted per aPTT, continued for 48 hours or until PCI 1
• Bivalirudin: 0.10 mg/kg loading dose, then 0.25 mg/kg/hour (only for early invasive strategy), continued until angiography or PCI 1

Critical caveat: If PCI is performed while on fondaparinux, administer additional anticoagulant with anti-IIa activity (UFH or bivalirudin) due to catheter thrombosis risk. 1

Do not crossover between UFH and LMWH. 1

Never administer IV fibrinolytic therapy in NSTEMI—this is harmful. 1

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Timing of Invasive Strategy

Immediate Invasive Strategy (<2 hours)

Proceed to immediate coronary angiography if any of the following very high-risk criteria are present:

• Hemodynamic instability or cardiogenic shock 1
• Recurrent or refractory chest pain despite medical treatment 1
• Life-threatening arrhythmias 1
• Mechanical complications 1

Early Invasive Strategy (Within 24-48 hours)

An early invasive strategy is indicated for patients with:

• Elevated cardiac biomarkers (troponin) 1, 2
• High GRACE or TIMI risk score 2
• Hemodynamic or electrical instability 2
• Refractory angina 2

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Peri-Procedural Management During PCI

Anticoagulation During PCI

Administer weight-adjusted UFH during PCI: 70-100 IU/kg IV bolus (or 50-70 IU/kg if using GP IIb/IIIa inhibitor), targeting ACT 250-350 seconds (or 200-250 seconds with GP IIb/IIIa inhibitor). 1

• If already on enoxaparin, continue with 0.5 mg/kg IV bolus at time of PCI 1
• If on fondaparinux, add UFH bolus at time of PCI 1

Antiplatelet Therapy at PCI

If not already loaded, administer P2Y12 inhibitor loading dose after coronary anatomy is determined. 1

• In high-risk patients (elevated troponin) adequately pretreated with clopidogrel and receiving UFH, it is reasonable to administer GP IIb/IIIa inhibitor (eptifibatide or tirofiban) at time of PCI 1

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Post-PCI and Maintenance Therapy

Dual Antiplatelet Therapy (DAPT)

Continue DAPT with aspirin (75-100 mg daily) plus P2Y12 inhibitor for 12 months after coronary stent implantation unless excessive bleeding risk exists. 1

• Ticagrelor or prasugrel are preferred over clopidogrel for post-PCI management 1
• If bleeding risk outweighs benefit, earlier discontinuation (<12 months) is reasonable 1

Anticoagulation Post-PCI

Discontinue anticoagulation after PCI unless there is a compelling indication (e.g., atrial fibrillation) to continue. 1

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Special Population: NSTEMI with Atrial Fibrillation

For patients with NSTEMI, atrial fibrillation (CHA₂DS₂-VASc ≥2 in men or ≥3 in women), and especially those with non-obstructive CAD:

• Initiate dual therapy with DOAC (apixaban 5 mg twice daily, rivaroxaban 15 mg once daily, edoxaban 60 mg once daily, or dabigatran 150 mg twice daily) plus clopidogrel 75 mg daily for up to 1 week post-event 1, 5
• Avoid triple therapy (aspirin + clopidogrel + anticoagulant) beyond 1 week due to dramatically increased bleeding risk 1, 5
• Transition to DOAC monotherapy after 12 months 1, 5
• Do not use ticagrelor or prasugrel as part of triple antithrombotic therapy 1
• Calculate HAS-BLED score (≥3 indicates high bleeding risk) and implement bleeding risk reduction measures including PPI therapy 5

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Long-Term Secondary Prevention

Cardiovascular Medications

Initiate ACE inhibitors for all patients with heart failure, LV dysfunction (LVEF <0.40), hypertension, or diabetes. 2

• Use ARBs for ACE inhibitor-intolerant patients 2
• Continue beta-blocker therapy indefinitely unless contraindicated 1
• Initiate high-intensity statin therapy for all NSTEMI patients 1

Pre-Operative Management for CABG

If urgent CABG is needed:

• Discontinue clopidogrel and ticagrelor for at least 24 hours before surgery to reduce major bleeding 1

If elective CABG is planned:

• Discontinue clopidogrel and ticagrelor for at least 5 days before surgery 1
• Discontinue prasugrel for at least 7 days before surgery 1
• Continue aspirin (81-325 mg daily) preoperatively 1

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Critical Pitfalls to Avoid

Never administer NSAIDs (except aspirin) during hospitalization—they increase mortality, reinfarction, hypertension, heart failure, and myocardial rupture risk. 2

Do not use immediate-release dihydropyridine calcium channel blockers without adequate beta-blockade. 2

Avoid concomitant use of clopidogrel with omeprazole or esomeprazole, as they significantly reduce clopidogrel's antiplatelet activity. 4

Do not use fondaparinux as sole anticoagulant during PCI due to catheter thrombosis risk. 1