Cardiovascular · Topic 3 of 48

NSTE-ACS (NSTEMI & Unstable Angina)

Cardiovascular · acute coronary syndrome

NSTE-ACS (NSTEMI & Unstable Angina)

Ischemia without ST elevation: antithrombotics now, risk-stratify, and time angiography to risk — immediate if unstable, within 24 hours if high risk. No fibrinolytics.

Key numbers

Unstable patient: immediate angiography≤ 2 h

High risk: cath within 24 hoursGRACE > 140 → < 24 h

Dual antiplatelet therapy for 12 months12 months

01 · What it isNSTEMI: troponin rise, no ST elevation

NSTE-ACS is ischemia without persistent ST elevation: NSTEMI has troponin above the 99th percentile with a rise and/or fall; unstable angina does not. The ECG may show ST depression, T-wave inversion or transient ST elevation.

02 · DoHigh risk: cath within 24 hours

GRACE score above 140, steeply rising troponin or dynamic ST changes → angiography within 24 hours; GRACE 109–140 → before discharge (within 72 hours); low risk → routine or selective invasive strategy.

03 · AvoidNo fibrinolytics in NSTE-ACS

Fibrinolytics benefit only STEMI; in unstable angina and NSTEMI they worsen outcomes, so reperfusion is by PCI or CABG after angiography.

Diagnosis & monitoring

Work-up

Unstable angina: rest, new or crescendo anginaUnstable angina presents as prolonged rest angina (usually over 20 minutes), new-onset angina of at least CCS class 3, or known angina that is clearly more frequent, longer or triggered by less exertion.

Do right now

In this order

First moves

Aspirin, P2Y12 inhibitor and anticoagulant

→

Nitroglycerin for ongoing ischemic pain

→

Unstable patient: immediate angiography≤ 2 h

→

High risk: cath within 24 hoursGRACE > 140 → < 24 h

Why each step

Aspirin, P2Y12 inhibitor and anticoagulantEvery NSTE-ACS patient without contraindication gets chewed non-enteric-coated aspirin 162–325 mg (then 81 mg daily), a P2Y12 inhibitor and a parenteral anticoagulant (unfractionated heparin or enoxaparin).

Nitroglycerin for ongoing ischemic painTreat ongoing pain with sublingual nitroglycerin 0.3–0.6 mg every 5 minutes up to 3 doses, then IV; withhold for SBP below 90 mmHg or a fall over 30 mmHg. Opioids only if refractory.

Unstable patient: immediate angiographyNSTE-ACS with cardiogenic shock, new or worsening heart failure, refractory angina, sustained VT/VF or hemodynamic instability needs immediate angiography with intent to revascularize — within 2 hours.

High risk: cath within 24 hoursGRACE score above 140, steeply rising troponin or dynamic ST changes → angiography within 24 hours; GRACE 109–140 → before discharge (within 72 hours); low risk → routine or selective invasive strategy.

Management

Orders

Prefer ticagrelor or prasugrel over clopidogrelFor ACS treated with PCI, ticagrelor (180 mg load, then 90 mg twice daily) or prasugrel (60 mg load, then 10 mg daily) is preferred over clopidogrel (300–600 mg load, then 75 mg daily).

Cath beyond 24 hours: start P2Y12 upstreamWhen angiography is planned more than 24 hours out, upstream clopidogrel or ticagrelor may be started to reduce events; prasugrel is reserved for patients proceeding to PCI.

Heparin for invasive strategy; enoxaparin otherwiseUnfractionated heparin (60–70 units/kg bolus, max 5000; 12–15 units/kg/h, max 1000) suits an early invasive strategy; enoxaparin or fondaparinux suit an ischemia-guided strategy — fondaparinux alone is not used for PCI.

Dual antiplatelet therapy for 12 monthsContinue aspirin plus a P2Y12 inhibitor for at least 12 months after ACS when bleeding risk is not high, and add a proton pump inhibitor for patients at GI bleeding risk.

Ticagrelor monotherapy after 1 monthTo reduce bleeding after PCI, patients who tolerate ticagrelor-based DAPT can stop aspirin at 1 month or later and continue ticagrelor alone (a Class 1 option in the 2025 ACS guideline).

On an anticoagulant: drop aspirin at 1–4 weeksPatients who need long-term oral anticoagulation (e.g., atrial fibrillation) stop aspirin 1–4 weeks after PCI and continue the anticoagulant — a DOAC preferred over warfarin — plus a P2Y12 inhibitor, preferably clopidogrel.

High-intensity statin; LDL-C goal under 55 mg/dLStart a high-intensity statin in hospital and add ezetimibe, a PCSK9 inhibitor, inclisiran or bempedoic acid until LDL-C reaches goal: < 55 mg/dL for very-high-risk ASCVD (most patients with ASCVD events), otherwise < 70 mg/dL.

Oral beta-blocker unless shock risk or blockGive an oral beta-blocker unless there is hypotension, bradycardia, heart block or asthma; avoid IV beta-blockers in patients at risk of cardiogenic shock. Benefit is limited when LVEF is preserved.

Low risk: stress test or CCTA allowedStable low-risk NSTE-ACS (including unstable angina without instability) may have angiography before discharge or noninvasive risk stratification with stress testing or CCTA, proceeding to angiography if abnormal.

Unstable angina or NSTEMI?

Commonly confused

Troponin	Not above the 99th percentile
Presentation	Rest angina > 20 min, new severe or crescendo angina
Fibrinolytics	Contraindicated
Antithrombotics	Aspirin, P2Y12 inhibitor, anticoagulant

More detail

Reference

Show 6 reference facts

Radial access is preferred over femoral for ACS PCI — fewer bleeding and vascular complications and lower mortality — and complete revascularization of significant lesions is recommended.

Glycoprotein IIb/IIIa inhibitors (eptifibatide, tirofiban) are reserved for PCI with high-risk lesions such as large thrombus burden or no-reflow.

With prior heparin-induced thrombocytopenia, use bivalirudin (or argatroban) for anticoagulation during PCI.

Ticagrelor is labeled for use with an aspirin maintenance dose of only 75–100 mg daily.

Red blood cell transfusion to a hemoglobin of 10 g/dL may be reasonable in ACS patients with acute or chronic anemia who are not actively bleeding.

TIMI and GRACE risk scores, combined with the troponin trend, symptoms and ECG, guide the timing of angiography versus an initial noninvasive approach.

Pearl

In NSTE-ACS the risk score sets the clock for the cath lab — and fibrinolytics are never the answer.

Sources · Merck Manual Professional — Overview of Acute Coronary Syndromes (risk stratification and management strategy for NSTE-ACS) · Merck Manual Professional — Unstable Angina · Merck Manual Professional — Medications for Acute Coronary Syndromes · Rao SV et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes (summary of key recommendations, Medical Dialogues, March 2025) · Ticagrelor tablets prescribing information — DailyMed · Rao SV et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. Circulation 2025;151:e771–e862 · Merck Manual Professional — Complications of Acute Coronary Syndromes · Cipla Med — ACC.25 panel: talking about the new ACS guidelines (upstream clopidogrel/ticagrelor Class 2b when angiography is not within 24 h; no prasugrel preloading) · Cleveland Clinic Consult QD — New guideline on acute coronary syndromes: key takeaways (Tamis-Holland, guideline vice chair; ticagrelor monotherapy after 1 month = Class 1) · EBM Consult — Contraindications to nitroglycerin in ACS (SBP < 90 mmHg or fall > 30 mmHg; recent PDE-5 inhibitor) · AJMC — AHA, ACC update guidelines for acute coronary syndrome management (Feb 2025) · AABB — New ACC/AHA guidelines include transfusion strategies for ACS management (Class 2b, Hgb ≥ 10 g/dL) · Guideline Central — 2026 ACC/AHA Management of Dyslipidemia Guideline: key highlights · EBSCO EBM Focus — Top takeaways from the updated ACC/AHA guideline on management of dyslipidemia (2026) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).