NSTEMI

Non-ST-elevation MI / unstable angina · complete reference · all trials · full doses + brand names · Full Card

Symptoms / Associated Sx

• Substernal pressure, squeezing, or tightness ± radiation to left arm, jaw, neck, or back; diaphoresis; dyspnea; nausea/vomiting; duration typically >20 minutes at rest (unlike stable angina which is <20 minutes and relieves with rest/NTG)

• NSTEMI = troponin rise above 99th percentile URL + ischemic symptoms ± ECG changes (no STE); UA (unstable angina) = ischemic symptoms + no troponin elevation ×2 (increasingly rare with hs-cTn; most UA on conventional troponin converts to NSTEMI with hs-cTn)

• High-risk clinical features: rest pain (>20 min); new onset angina CCS class III or IV; accelerating/crescendo pattern; recent MI (<2 weeks); signs of HF (Killip class ≥2); new MR murmur (papillary muscle ischemia); hemodynamic instability

• Atypical presentations (up to 30% of NSTEMI — particularly in elderly >75, women, diabetics, CKD): isolated dyspnea; fatigue; epigastric pain; jaw pain; syncope; new HF without chest pain — these patients are undertriaged and have worse outcomes

Neg

• Pt denies STE ≥1 mm in ≥2 contiguous leads or STEMI equivalents (new LBBB + Sgarbossa ≥5 pts; de Winter T-waves; posterior STEMI pattern; aVR STE ≥1 mm + 8-lead ST↓) — these require immediate cath lab activation; exit NSTEMI algorithm; do not manage STEMI equivalents as NSTEMI

• Pt denies tearing/ripping quality chest pain radiating between shoulder blades to the back + BP differential >20 mmHg between arms + widened mediastinum on CXR — argues against aortic dissection (CTA chest/abdomen/pelvis BEFORE any anticoag, heparin, or aspirin if dissection possible; RCA ostium dissection mimics inferior STEMI pattern)

• Pt denies sharp pleuritic/positional CP worsening with lying flat, relieved by leaning forward + audible pericardial friction rub + diffuse saddle ST↑ in multiple leads without focal territorial reciprocal changes — argues against pericarditis (pericarditis: PR depression; no focal WMA on echo; no territorial ECG distribution; troponin mildly elevated only in myopericarditis)

• Pt denies troponin elevation with a clear high-burden systemic precipitant (sepsis, AF-RVR, severe hypotension, severe anemia) without focal territorial ECG changes or focal WMA on echo — argues against pure Type 2 MI being managed incorrectly as NSTEMI (if cannot exclude Type 1, proceed with NSTEMI management; if Type 2 clear → treat precipitant; no DAPT without cath-confirmed obstructive CAD)

Social History (SHx)

• Prior CAD, ACS, PCI, CABG (stent type — BMS vs DES; date; vessel; CP within 30 days of PCI = stent thrombosis → cath immediately; prior cath anatomy — known severe stenoses determine ischemia likelihood); tobacco (current/former/pack-years); cocaine/stimulant use

• HTN, hyperlipidemia, DM, obesity, family history of premature CAD (M <55, F <65 — independent RF); current antiplatelet (which agent, dose, compliance) and anticoag; missed DAPT doses post-PCI (↑stent thrombosis risk); prior contrast allergy (N-acetylcysteine [Mucomyst] + IV hydration pre-procedure)

Main Etiology

• Type 1 MI mechanism (~80%): atherosclerotic plaque rupture or erosion → platelet aggregation + thrombus formation → partial or dynamic coronary occlusion; NSTEMI occurs when occlusion is incomplete or with abundant collateral supply; coronary emboli (AF, endocarditis) can produce identical presentation

• SCAD (spontaneous coronary artery dissection): young women, peripartum, fibromuscular dysplasia (FMD); intramural hematoma without atherosclerosis; avoid thrombolytics (propagate dissection); conservative management preferred if hemodynamically stable; coronary angiography approach carefully (avoid occlusive wiring)

• MINOCA (MI with non-obstructive coronary arteries): troponin + symptoms + normal coronaries (<50% stenosis) on cath; mandatory cardiac MRI within 1 week (myocarditis vs Takotsubo vs true ischemic MINOCA from vasospasm or embolism); do NOT reflexively start DAPT — etiology determines management

RF

• Traditional: tobacco (strongest modifiable RF — ↑ACS risk 2–4×), HTN (most important chronic modifiable RF), hyperlipidemia (LDL >190 = very high risk), DM (↑plaque burden + silent ischemia), age (M ≥45, F ≥55), family hx premature CAD (M <55, F <65), obesity

• Non-traditional: CKD (eGFR <60 = CAD risk equivalent; ↑uremic toxins → ↑plaque vulnerability; ↑bleeding risk complicates anticoag), RA/SLE (chronic inflammation → accelerated atherosclerosis), HIV (antiretrovirals + chronic inflammation → ↑ACS risk), OSA (untreated → nocturnal hypoxemia + ↑sympathetic tone), cocaine/stimulants (coronary vasospasm + thrombosis + HTN), Lp(a) >50 mg/dL (independent high-risk RF)

Data

• ECG — on arrival + repeat q6–8h + with every symptom recurrence (ST↓ ≥0.5 mm or T-wave inversions = high-risk NSTEMI (TIMI score +2 for ST↓); new LBBB = STEMI equivalent; compare to prior ECG; dynamic ECG changes = highest risk feature; aVR STE ≥1 mm + diffuse ST↓ ≥8 leads = left main/proximal LAD pattern; Wellens syndrome in pain-free state = critical LAD stenosis → urgent cath)

• hs-cTn 0h + 1h (or standard troponin 0h + 3h) (NSTEMI = above 99th percentile URL + ischemic sx + rising and/or falling pattern; UA = ischemic sx + negative troponin ×2; troponin trend: rising = active ischemia; peak then decline = completed infarction; re-elevation = reinfarction; always note exact values and trend, not just "positive" vs "negative")

• GRACE Risk Score (gracescore.org) — calculate at presentation (8 variables: age + heart rate + SBP + creatinine + Killip class + cardiac arrest at presentation + ST deviation + elevated cardiac markers; GRACE >140 = high risk → early invasive strategy within 2–24h [Class I]; GRACE 109–140 = intermediate; GRACE <109 = low; superior to TIMI for in-hospital and 6-month mortality prediction; use online calculator for accuracy)

• TIMI Risk Score for UA/NSTEMI (7 binary variables [1 point each]: age ≥65; ≥3 CAD risk factors; prior coronary stenosis ≥50%; ST deviation ≥0.5 mm on presentation ECG; ≥2 anginal events in prior 24h; ASA use in past 7 days [aspirin failure]; elevated cardiac markers; MACE at 14 days: 0–2 = 4.7%; 3–4 = 13%; 5–7 = 40.9%)

• BMP (K+ — arrhythmia risk; Cr — CRITICAL: enoxaparin [Lovenox] dose reduction required if CrCl 15–30; fondaparinux [Arixtra] preferred in high bleed risk; contrast nephropathy risk stratification; glucose — hyperglycemia ↑post-MI mortality; Na+ — prognosis if HF)

• CBC (Hgb — bleeding risk with DAPT + anticoag; anemia → MINT protocol: Hgb ≥10 target in ACS; platelets — ≥70,000 safe for DAPT; <50,000 → anticoag dose reduction + hematology)

• Coagulation studies (baseline INR/PTT; anti-Xa level if on LMWH; identify patients on anticoag before DAPT initiation)

• Lipid panel + HbA1c (LDL target <70 mg/dL; <55 mg/dL if recurrent ACS; atorvastatin [Lipitor] 80 mg or rosuvastatin [Crestor] 40 mg daily immediately; if LDL still above goal → add ezetimibe [Zetia] 10 mg or PCSK9i [evolocumab (Repatha)/alirocumab (Praluent)])

• Type + screen (pre-procedure blood preparation; 2 units pRBC on hold if EF <30% or prior CABG)

• CXR portable (pulmonary edema — Killip class ≥2; cardiomegaly; widened mediastinum — dissection; pneumothorax; pleural effusion)

• Echo (TTE) (EF — CRITICAL for risk stratification; regional WMA = ischemic territory; new MR — papillary muscle ischemia; pericardial effusion; RV function; IVC — volume; if hemodynamically unstable → immediate bedside echo)

DDx

STEMI (STE ≥1 mm ≥2 leads or STEMI equivalents — cath lab immediately; do not manage as NSTEMI) · Type 2 MI (clear systemic precipitant; focal ECG absent; global vs focal WMA on echo; treat precipitant; DAPT only if cath confirms obstructive CAD) · Aortic dissection (tearing back pain + BP differential >20 mmHg — CTA BEFORE any anticoag; RCA ostium mimics inferior STEMI) · Pericarditis/myopericarditis (diffuse saddle ST↑ + PR↓ + pleuritic + friction rub; troponin mildly elevated in myopericarditis only; no territorial WMA) · PE (pleuritic CP + hypoxia + tachycardia + RV dilation on echo — CT-PA; troponin elevated from RV strain) · Takotsubo CM (stressor + older women + apical ballooning on echo + normal coronaries on cath) · MINOCA (troponin + symptoms + normal coronaries on cath — cardiac MRI within 1 week mandatory; myocarditis vs Takotsubo vs true ischemic)

Home Meds

• Hold: NSAIDs (ibuprofen [Advil]/naproxen [Aleve]/celecoxib [Celebrex] — avoid indefinitely post-ACS; ↑CV events; ↑GI bleed with DAPT); PDE5 inhibitors (sildenafil [Viagra] ×24h, tadalafil [Cialis] ×48h before NTG); metformin (Glucophage) if Cr elevated or contrast planned (restart 48h post-cath if Cr stable)

• Continue (do NOT stop): BB (carvedilol [Coreg]/metoprolol succinate [Toprol-XL]) — abrupt BB discontinuation → rebound ischemia → ↑MI risk; ACEi/ARB; statins (atorvastatin [Lipitor]/rosuvastatin [Crestor]); aspirin (Bayer) if already taking

• Existing anticoagulants: discuss post-cath DAPT + anticoag timing with cardiology (triple therapy — aspirin [Bayer] + P2Y12 + anticoag — ↑major bleeding 3–4×; minimize triple therapy duration per ACC/AHA guidelines)

Plan

• Risk stratification — immediate (determines everything): GRACE score (gracescore.org) + TIMI + clinical assessment; cardiology consult for all confirmed NSTEMI; invasive vs conservative strategy + timing; NPO if early invasive planned

• Monitoring: IV ×2; continuous cardiac monitoring (telemetry); O2 only if SpO2 <90% (avoid routine O2 in normoxic patients); continuous BP monitoring

• Aspirin (Bayer/Ecotrin): 325 mg PO chewed ×1 immediately → 81 mg PO daily indefinitely; give before any diagnostic workup results; aspirin irreversibly inhibits COX-1 → ↓thromboxane A2 → ↓platelet aggregation | Hold ALL P2Y12 agents until coronary anatomy confirmed by cath — CABG required in 5–10% of NSTEMI; prasugrel [Effient] and ticagrelor [Brilinta] require 5–7 day washout before CABG; premature P2Y12 loading = major surgical delay + bleeding if CABG needed

• P2Y12 selection (after PCI confirmed):

  • Ticagrelor (Brilinta) 180 mg PO ×1 → 90 mg PO BID ×12 months (preferred — PLATO 2009, NEJM: ↓CV death/MI/stroke 16% vs clopidogrel [Plavix]; ↓CV death alone 21%; keep ASA dose ≤100 mg/day with ticagrelor [Brilinta]; avoid in prior intracranial hemorrhage)

  • Prasugrel (Effient) 60 mg PO ×1 → 10 mg PO daily ×12 months (NSTEMI post-PCI only — TRITON-TIMI 38: more potent than clopidogrel [Plavix] in PCI setting; NEVER administer pre-cath in NSTEMI — ↑life-threatening bleeding without ↓ischemic events; contraindicated: age ≥75, weight <60 kg, prior stroke/TIA)

  • Clopidogrel (Plavix) 600 mg PO ×1 → 75 mg PO daily ×12 months (if ticagrelor/prasugrel contraindicated — CURE 2001: ↓CV events vs ASA alone; CYP2C19 poor metabolizers have ↓response — test if available; acceptable after CABG if no other option)

• Anticoagulation (choose one):

  • Enoxaparin (Lovenox) 1 mg/kg SQ q12h (preferred — SYNERGY 2004: ≥UFH for composite MACE; ↓recurrent MI; reduce to 1 mg/kg SQ daily if CrCl 15–30; AVOID CrCl <15; anti-Xa monitoring if CrCl <30 or BMI >40 or weight <45 kg)

  • UFH 60 units/kg IV bolus (max 4,000 units) → 12 units/kg/hr infusion (max 1,000 units/hr; titrate aPTT 50–70 seconds; preferred if urgent CABG anticipated — rapid reversal with protamine sulfate; preferred in CrCl <15; preferred in hemodynamic instability)

  • Fondaparinux (Arixtra) 2.5 mg SQ daily (OASIS-5 2006, NEJM: ↓major bleeding 50% vs enoxaparin [Lovenox] with equivalent ischemic outcomes; preferred in very high bleed risk [GI bleed, thrombocytopenia, prior CABG]; MUST add UFH 50 units/kg IV bolus at time of PCI — catheter thrombosis risk with fondaparinux alone at PCI site; avoid CrCl <20)

• Invasive strategy timing:

  • Immediate (<2h): refractory ischemia (ongoing CP despite max medical Rx); hemodynamic instability (cardiogenic shock, SBP <90); life-threatening arrhythmia (sustained VT/VF); acute pulmonary edema

  • Early (2–24h): GRACE >140 (TIMACS 2009, NEJM: early invasive ↓refractory ischemia/MI; greatest benefit in GRACE >140; Class I, Level A); TIMI ≥3; elevated troponin; ST↓ ≥0.5 mm on ECG; EF <40%

  • Delayed (25–72h): GRACE 109–140; moderate-risk features; stable after initial medical management

  • Conservative (selective): GRACE <109; TIMI 0–1; negative troponin ×2; no high-risk features; low-risk women (ICTUS 2005: no benefit of early invasive in low-risk NSTEMI); still requires stress testing or CTCA before discharge

• Anti-ischemic therapy: nitroglycerin (NTG SL/Nitro-Bid) 0.4 mg SL q5 min ×3 PRN (hold if SBP <90, suspected RV MI, PDE5i within 24–48h); IV NTG (Nitro-Bid) 5–200 mcg/min if refractory ischemia/HTN/pulm edema; metoprolol tartrate (Lopressor) 25–50 mg PO q6–8h → metoprolol succinate (Toprol-XL) 25–100 mg PO daily within 24h (hold if SBP <100, HR <60, PR >0.24, active HF decompensation, bronchospasm); morphine (MSIR) AVOID — IMPRESSION trial (2016): morphine ↓ticagrelor [Brilinta] peak plasma level ~36% via ↓GI motility → ↑platelet reactivity; CRUSADE registry: morphine ↑in-hospital mortality; use IV fentanyl (Sublimaze) 25–50 mcg q15 min PRN for pain

• Statins + ACEi + eplerenone (initiate on admission):

  • Atorvastatin (Lipitor) 80 mg PO daily (PROVE-IT 2004, NEJM: intensive atorvastatin [Lipitor] 80 mg ↓CV events vs pravastatin [Pravachol] 40 mg; NNT 25; begin immediately regardless of baseline LDL; target LDL <70 mg/dL; <55 mg/dL if recurrent ACS — add ezetimibe [Zetia] 10 mg PO daily or PCSK9i if above goal)

  • Lisinopril (Zestril/Prinivil) 2.5→10–20 mg PO daily (GISSI-3, ISIS-4: ACEi ↓30-day mortality post-MI; continue indefinitely if EF ≤40%, HTN, or DM; hold if SBP <100 or ↑Cr)

  • Eplerenone (Inspra) 25→50 mg PO daily starting at Day 30 post-MI if EF ≤40% + HF symptoms or DM (EPHESUS 2003: ↓CV death 15%, ↓SCD 21%; hold if K+ >5.0 or Cr >2.5M/>2.0F)

• MINOCA management (normal coronaries + troponin on cath): cardiac MRI within 1 week (mandatory — most important diagnostic step); ACEi + statin standard; DAPT only if true ischemic MINOCA (vasospasm/embolism); provocation testing (ergonovine or acetylcholine) for vasospasm; CCB (amlodipine [Norvasc] or diltiazem [Cardizem]) if vasospasm confirmed

• PT/OT eval and treat — early ambulation as hemodynamically tolerated; functional capacity assessment; cardiac rehab referral (NACR trial: cardiac rehab ↓mortality 26%)

• Trend daily: BMP (K+ — target ≥4.0 with DAPT; Cr — enoxaparin [Lovenox] dose; glucose); CBC (Hgb — MINT protocol: Hgb ≥10 in ACS + anemia); troponin q3–6h until clear peak then plateau (re-elevation = reinfarction → urgent repeat cath); ECG daily + with any symptom; LFTs at 1 week (statin monitoring); fever curve — Days 2–6 = Dressler pericarditis; Days 5+ = infection/drug fever

• Escalation triggers: refractory ischemia (ongoing CP + ECG changes despite max medical Rx including NTG + anticoag + BB) → immediate cath regardless of initial conservative strategy decision · hemodynamic instability (SBP <90, MAP <65, lactate >2) → CCU + MCS (Impella CP [Abiomed] or IABP [Datascope]) · sustained VT/VF → amiodarone (Pacerone) 150 mg IV → 1 mg/min ×6h + defibrillation · new systolic murmur → emergency echo (papillary muscle rupture = MR; VSD = new harsh holosystolic murmur) → surgical emergency + IABP bridge · troponin re-elevation after initial decline → reinfarction/stent thrombosis → urgent repeat cath · cardiogenic shock → CCU + early PCI (SHOCK trial: ↓1-year mortality)

• Discharge: aspirin (Bayer) 81 mg PO daily indefinitely + ticagrelor (Brilinta) 90 mg PO BID ×12 months (or clopidogrel [Plavix] 75 mg if ticagrelor contraindicated); metoprolol succinate (Toprol-XL) titrated to HR 55–65 bpm; ACEi (lisinopril [Zestril] 10–20 mg PO daily) or ARB (valsartan [Diovan] 80–160 mg BID) if ACEi intolerant; atorvastatin (Lipitor) 80 mg PO daily (+ ezetimibe [Zetia] 10 mg PO daily if LDL >70 mg/dL on statin alone; + evolocumab [Repatha] 140 mg SQ q2 weeks or alirocumab [Praluent] 75–150 mg SQ q2 weeks if LDL >55 mg/dL on statin + ezetimibe); eplerenone (Inspra) 50 mg PO daily if EF ≤40% at 30 days; nitroglycerin (NTG SL) 0.4 mg q5 min ×3 PRN + return if not relieved; cardiac rehab (Class I — NACR: ↓mortality 26%, ↓rehospitalization, ↑QoL); ICD evaluation at 40 days if EF ≤35% after GDMT (MADIT-II, SCD-HeFT); cardiology f/u 1–2 weeks; no driving 24–48h post-PCI (4 weeks if EF impaired or arrhythmia); dietary counseling (<2 g Na+/day; Mediterranean diet); smoking cessation (varenicline [Chantix] 0.5 mg PO daily ×3 days → 0.5 mg BID ×4 days → 1 mg BID ×12 weeks); ACS symptom recognition + return precaution education

⚠ Red Flags

• Refractory ischemia (ongoing CP + ECG changes despite max medical therapy including NTG + anticoag + BB) → immediate coronary angiography regardless of initial conservative strategy — delay worsens outcomes; this is the most common indication to upgrade from conservative to early invasive in NSTEMI

• STEMI equivalents mismanaged as NSTEMI (Wellens syndrome, de Winter T-waves, posterior STEMI with ST↓ V1–V3, aVR STE + 8-lead ST↓) → these require cath lab activation, not NSTEMI medical management; know the STEMI equivalents at the bedside

• Prasugrel (Effient) given pre-cath in NSTEMI → TRITON-TIMI 38 showed ↑life-threatening bleeding pre-cath without ↓ischemic events; NEVER administer prasugrel (Effient) before coronary anatomy is confirmed; CABG washout requirement is 7 days for prasugrel

• Morphine (MSIR/MS Contin) administered for pain in NSTEMI → IMPRESSION trial: morphine ↓ticagrelor (Brilinta) peak plasma concentration ~36% via ↓GI motility → ↑residual platelet reactivity → worse outcomes; use IV fentanyl (Sublimaze) 25–50 mcg PRN instead

• New systolic murmur post-NSTEMI → emergency echo; papillary muscle rupture (posterior more common — RCA territory; acute severe MR → pulmonary edema + cardiogenic shock → surgical emergency); VSD (harsh holosystolic murmur + left-to-right shunt → RV failure → surgical emergency); IABP bridge to surgery in both

• Troponin re-elevation after initial decline → reinfarction or stent thrombosis; urgent repeat coronary angiography; every minute of delay = additional myocardial loss

• Aortic dissection mismanaged as ACS (given thrombolytics or heparin) → massive hemorrhage + death; always consider dissection before anticoag in any patient with CP + tearing quality + BP differential or widened mediastinum

Senior IM Resident Pearls

• GRACE score — use it every time (gracescore.org): 8 variables: age, heart rate, SBP, creatinine, Killip class, cardiac arrest at presentation, ST deviation, elevated troponin; GRACE >140 = high risk → early invasive within 24h (Class I, Level A); superior to TIMI for mortality prediction; 30-second calculation on gracescore.org; document in chart; determines everything downstream

• TIMI Risk Score for UA/NSTEMI — 7 binary variables (1 pt each): age ≥65; ≥3 CAD RFs; prior stenosis ≥50%; ST deviation ≥0.5 mm; ≥2 anginal events in 24h; ASA in past 7 days (aspirin failure); elevated troponin; MACE at 14 days: 0–2 = 4.7%, 3–4 = 13%, 5–7 = 40.9%; quick bedside calculation; use alongside GRACE

• P2Y12 timing — the most critical antiplatelet decision in NSTEMI: early invasive strategy → hold P2Y12 until post-cath (CABG in 5–10%; prasugrel [Effient] and ticagrelor [Brilinta] require 5–7 day washout pre-CABG → major surgical delay + mortality risk); conservative strategy → load P2Y12 upfront; PRASUGREL RULE: NEVER pre-cath in NSTEMI — TRITON-TIMI 38 showed ↑life-threatening bleeding without ↓ischemic events pre-cath

• PLATO (2009, NEJM): ticagrelor (Brilinta) vs clopidogrel (Plavix) in ACS → ↓CV death/MI/stroke 16% (NNT 54); ↓CV mortality 21%; ↓all-cause mortality 22%; keep ASA ≤100 mg/day (higher ASA dose ↓ticagrelor benefit — the "North American paradox"); ticagrelor (Brilinta) is preferred P2Y12 in NSTEMI unless contraindicated; side effects: dyspnea (10–15%, benign, often resolves), ventricular pauses (usually asymptomatic)

• OASIS-5 (2006, NEJM): fondaparinux (Arixtra) vs enoxaparin (Lovenox) in NSTEMI → equivalent ischemic outcomes at 9 days; fondaparinux ↓major bleeding 50%; preferred in very high bleed risk (GI bleed, thrombocytopenia, elderly frail); MUST add UFH 50 units/kg IV at PCI (catheter thrombosis with fondaparinux alone)

• Morphine avoidance — IMPRESSION trial (2016): morphine co-administration with ticagrelor (Brilinta) → ↓ticagrelor peak plasma level ~36% (↓GI motility → ↓absorption) → ↑residual platelet reactivity; CRUSADE registry: morphine ↑in-hospital mortality in NSTEMI; use IV fentanyl (Sublimaze) 25–50 mcg PRN — faster onset, short duration, no GI motility effect

• TIMACS (2009, NEJM): early invasive (≤24h) vs delayed (≥36h) in NSTEMI + moderate-high risk → early invasive ↓composite refractory ischemia/MI/death at 6 months (primarily ↓refractory ischemia); greatest benefit in GRACE >140 (↓death/MI/stroke 35%); no benefit in GRACE <109 (low-risk patients); timing of invasion matters — know your GRACE score

• Common mistake — loading P2Y12 before coronary anatomy confirmed: CABG required in 5–10% of NSTEMI; prasugrel (Effient) washout = 7 days, ticagrelor (Brilinta) washout = 5 days before CABG; premature loading → surgical delay + ↑bleeding if CABG needed; always hold P2Y12 until post-cath in early invasive strategy; this is the most consequential antiplatelet decision in NSTEMI management