← Master Index· Section 2 · Cardiovascular Disorders · Chapter 5

Acute Coronary Syndromes

STEMI · NSTEMI · UADAPTFibrinolysis vs PCIDiPiro Ch 5 + IDT II 753

30-Second Snapshot

What it is:Acute myocardial ischemia from a mismatch between oxygen demand and supply. A plaque ruptures, platelets pile onto the exposed collagen, thrombin builds a fibrin mesh around them, and blood flow abruptly drops.

Three flavors, split by ECG and troponin:STEMI (ST elevation + troponin), NSTEMI (troponin, no ST elevation), unstable angina (symptoms, no troponin).

The clock is the treatment.STEMI carries the highest short-term mortality and goes straight to reperfusion. Do not wait for troponin to come back before acting.

The one branch point that organizes everything

ST elevation → the artery is completely occluded → open it NOW(primary PCI, or fibrinolysis if PCI isn't reachable in time).
No ST elevation → the artery is partially occluded with residual flow → you have hours, not minutes.Risk-stratify, then choose early invasive or ischemia-guided.

Pathophysiology

Why "stable" plaques are the dangerous ones

Plaques that rupture typically have thin fibrous caps and are nonobstructive, occluding under 70% of the lumen. That's counterintuitive but important: because the narrowing is modest, autoregulation keeps flow adequate even during exertion, so many patients never had angina before the event. A surge of catecholamines during physical or emotional stress can be what tips a thinning cap into rupture.

The cascade after rupture

  1. Adhesion.The barrier between the necrotic plaque core and the blood is breached. Platelets bind via GP VI to collagenin the damaged cap, and via GP Ib-IX to von Willebrand factor.
  2. Activation.Collagen, thrombin, thromboxane A₂, ADP, epinephrine, and serotonin activate platelets through their receptors - P2Y₁₂ for ADP, PAR-1 for thrombin. Platelets change shape, expand surface area, and dump more activators from their granules.
  3. Thrombin generation.Tenase and prothrombinase complexes assemble on activated platelets, producing most of the factor Xa and thrombin.
  4. Aggregation.GP IIb/IIIareceptors change conformation and cross-link platelets to each other through fibrinogen bridges- the platelet plug.
  5. Stabilization.The clotting cascade lays a fibrin meshwork around the plug, trapping red cells. Flow drops abruptly. Untreated, myocyte necrosis follows.
Read the drug classes off the cascade

Aspirinblocks thromboxane A₂. P2Y₁₂ inhibitorsblock the ADP receptor. GP IIb/IIIa inhibitorsblock the final common aggregation step. Heparins and bivalirudinblock thrombin. Four drug classes, four sequential points on one pathway - which is exactly why you use more than one at once.

The five MI subtypes (by etiology)
  1. Type 1:rupture, fissure, or erosion of an atherosclerotic plaque - 90% of cases.
  2. Type 2:supply/demand mismatch withouta coronary artery process (sepsis, severe anemia, tachyarrhythmia, hypotension).
  3. Type 3:MI resulting in death before biomarkers could be measured.
  4. Type 4:PCI-associated (4a) or stent thrombosis (4b).
  5. Type 5:CABG-associated.

This matters clinically: a Type 2 MI in a septic patientis treated by fixing the sepsis, not by cath lab activation.

Post-MI remodeling

SNS and RAAS activation compensate for reduced cardiac output acutely, but chronic hyperactivation causes ventricular hypertrophy and further impairs contractility. Inflammatory mediators and collagen deposition produce fibrosis and scarring, thinning the LV wall and potentially causing dilated cardiomyopathy. This is why ACE inhibitors and beta blockers are secondary prevention, not just BP drugs.

Clinical Presentation

Classic:abrupt substernal chest pain or discomfort - squeezing, heaviness, tightness - persisting 10 minutes or longer. Radiates to arms and shoulders (especially left), back, abdomen, or jaw. Often with nausea, vomiting, diaphoresis, or shortness of breath.

Atypical presentations - who and what

Who:older adults, women, patients with diabetes, impaired renal function, or dementia.
What:epigastric pain, indigestion, pleuritic chest pain, increasing exertional dyspnea - withoutchest pain at all. Missing these is a major source of delayed diagnosis.

Physical exam:nothing is specific to ACS. Nonspecific findings include S4or paradoxical splitting of S2. Signs of acute decompensated HF include JVD, pulmonary edema, and S3. Patients may present with arrhythmias, heart block, hypertension, hypotension, or shock.

Diagnosis

The 10-minute rule

12-lead ECG within 10 minutes of presentation.Prehospital ECG if possible. This single step determines whether the patient goes to the cath lab immediately or gets risk-stratified.

ECG findings

Troponin

DiagnosisECGTroponin
STEMIST elevation ≥1 mm in 2 contiguous leads, or new LBBBElevated, dynamic
NSTEMINo ST elevation (may have depression or T inversion)Elevated
Unstable anginaNo ST elevationNot elevated
The differentiator is troponin, not symptoms

NSTEMI and unstable angina present identically. The onlything separating them is whether troponin rose. And STEMI is separated from both by the ECG, not the troponin - which is why you never delay reperfusion waiting for a troponin result.

Other baseline labs:renal function (identifies dose adjustments and high-risk patients), potassium and magnesium (rhythm), CBC, fasting lipid panel, and coagulation tests (aPTT or anti-Xa, INR) since nearly everyone gets antithrombotics.

Acute Supportive Care - Everyone Gets This

InterventionDoseNotes
Aspirin162–325 mg non-enteric-coated, chewed and swallowedAll ACS patients without contraindication, any type, any strategy. Chewing gets platelet inhibition in <30 min. Then 81 mg daily indefinitely
Nitroglycerin SL0.3–0.4 mg q5min × up to 3 doses PRNFor angina, uncontrolled HTN, acute HF
Nitroglycerin IVStart 10 mcg/min, titrate to symptoms and BPFor persistent angina despite SL. Continue until symptoms resolve, BP controlled, HF subsided. Taper graduallyon discontinuation
Oxygen2–4 L/min, only if SaO₂ <90%Routine use may harm- increases coronary vascular resistance and reduces coronary blood flow
MorphineSTEMI: 4–8 mg IV × 1 (lower if elderly), then 2–8 mg q5–15 min PRN
NSTE-ACS: 1–5 mg q5–30 min, only if refractoryto other anti-ischemics
Role is uncertain - some studies show adverse outcomes
Beta blocker (oral)Within first 24 hoursAll patients without contraindications. Continue ≥3 yearsif normal LVEF; often lifelong if LVEF <40%
Two hard contraindications

Nitrates are contraindicatedin anyone who recently took a PDE-5 inhibitor (sildenafil, tadalafil, vardenafil). Ask directly - profound hypotension otherwise.
Aspirin contraindicationsare hypersensitivity and major GI intolerance. In those cases use clopidogrel with a loading dose instead.

"MONA" is outdated

The old mnemonic implies you give all four to everyone in that order. Reality: aspirinis the only one that's genuinely universal and outcome-improving. Oxygenis now restricted to SaO₂ <90% because routine use may cause harm. Morphinehas uncertain benefit and is second-line in NSTE-ACS. Nitratesrelieve symptoms but don't reduce mortality.

Beta blocker dosing

Calcium channel blockers

Anti-ischemic but no proven mortality benefit. Use non-dihydropyridines (diltiazem 120–360 mg/day, verapamil 240–480 mg/day)for angina in patients who are intolerant of, contraindicated to, or refractory to beta blockers - but onlyin the absence of LV dysfunction, cardiogenic shock risk, or AV conduction defects. Long-acting CCBs for known or suspected vasospasm (amlodipine 5–10 mg, nifedipine ER 30–120 mg, nicardipine 60–120 mg/day).

‍ STEMI - Reperfusion Strategy

PREFERRED

Primary PCI

Within 90 minutesof first medical contact. If transfer needed, within 120 minutes.
IF PCI UNREACHABLE

Fibrinolysis

When PCI can't happen within 120 min. Give within 30 min of hospital arrival.

Why PCI wins:compared to fibrinolysis it improves survival, gives consistent revascularization of the infarct artery, reduces stroke and intracranial hemorrhage, and reduces reinfarction and recurrent ischemia.

Fibrinolytic agents

AgentDose
Alteplase15 mg IV bolus over 1–2 min → 0.75 mg/kg (max 50 mg) over 30 min → 0.5 mg/kg (max 35 mg) over 60 min. Max total 100 mg
Reteplase10 units IV over 2 min, repeat 10 units 30 min later
TenecteplaseSingle IV bolus over 5 sec by weight: <60 kg → 30 mg · 60–69.9 → 35 mg · 70–79.9 → 40 mg · 80–89.9 → 45 mg · ≥90 kg → 50 mg

Fibrin-specific agents(alteplase, reteplase, tenecteplase) are preferred over streptokinasebecause of greater reperfusion success and less systemic bleeding.

Absolute contraindications to fibrinolysis
  • Any prior hemorrhagic stroke
  • Ischemic stroke within 3 months
  • Intracranial neoplasm or AV malformation
  • Active internal bleeding
  • Aortic dissection
  • Considerable facial or closed head trauma in past 3 months
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled hypertension
  • For streptokinase: prior treatment within 6 months

Primary PCI is preferred in all of these situations.Between 12 and 24 hours after symptom onset, limit fibrinolysis to patients with ongoing clinical or ECG evidence of ischemia.

Intracranial hemorrhage risk

Fibrinolysis carries a 0.9–1.0%ICH rate. Predictors: advanced age, lower body weight, female sex, preexisting cerebrovascular disease, and systolic or diastolic hypertension at presentation.

NSTE-ACS - Invasive vs Ischemia-Guided

These patients typically have a partially occludedartery with residual perfusion, so the urgency to open it is lower.

StrategyWhoWhat happens
Early invasiveIntermediate to high risk for death, MI, refractory angina, acute HF, cardiogenic shock, or arrhythmiasDiagnostic angiography within 24 hours, revascularize if appropriate
Ischemia-guided(medical management)Select low-riskpatientsAntiplatelet + anticoagulant, no planned PCI. Noninvasive stress testing; angiography only if symptoms recur or instability develops

P2Y₁₂ choice in NSTE-ACS

Antiplatelet Therapy

Both antiplatelet andanticoagulant therapy are needed acutely, because platelets dominate arterial thrombosis while thrombin drives both platelet activation and coagulation. After discharge, most patients continue antiplatelet only.

Aspirin

P2Y₁₂ inhibitors

AgentLoading doseMaintenanceNotes
Clopidogrel600 mgbefore primary PCI
300 mgwith fibrinolysis or no reperfusion
No loading dose if age ≥75
75 mg dailyThe only agent studied in large trials with fibrinolysis
PrasugrelPer protocol, at time of PCIDailyMore potent. Avoid with prior stroke/TIA; caution age ≥75 and low body weight
TicagrelorLoading doseTwice dailyReversible. Dyspnea is a characteristic side effect
CangrelorIVIV infusionAdjunct to PCI in patients noton an oral P2Y₁₂ inhibitor or planned GP IIb/IIIa inhibitor
Two details that get tested

1.With fibrinolysis, use clopidogrel- it's the only P2Y₁₂ inhibitor with large-trial evidence in that setting. Any of the four can be used with primary PCI.
2.No clopidogrel loading dose in patients ≥75 years old.Go straight to maintenance.

GP IIb/IIIa inhibitors

Considered during PCI when no P2Y₁₂ inhibitor was given beforehand, or in high-risk NSTE-ACS. They block the final common aggregation step, so bleeding risk is meaningful and they've become more selective in modern practice.

Parenteral Anticoagulation

SettingOptions
STEMI - primary PCIUFHor bivalirudin; may switch to bivalirudin during PCI
STEMI - fibrinolysisUFHor LMWH
NSTE-ACS - early invasiveUFHor LMWH, may switch to bivalirudin during PCI
NSTE-ACS - ischemia-guidedFondaparinux, LMWH, or UFH
Fondaparinux has a narrow lane here

It appears in the ischemia-guided NSTE-ACSpathway, not in the PCI pathways, because of catheter thrombosis risk when used alone during PCI. If a patient on fondaparinux goes to the cath lab, additional anticoagulation with anti-IIa activity is needed.

Secondary Prevention - The Discharge Bundle

Every ACS patient should leave on this unless contraindicated. This is a very common exam and rotation question.

Drug classWhyDuration
Aspirin 81 mg dailyAntiplateletIndefinitely
P2Y₁₂ inhibitorDAPT prevents stent thrombosis and recurrent eventsTypically 12 months, individualized by bleeding vs ischemic risk
High-intensity statinEstablished ASCVD = secondary preventionIndefinitely. Atorvastatin 40–80 or rosuvastatin 20–40
Beta blockerReduces angina, MI, arrhythmias; limits remodeling≥3 yearsif normal LVEF; often lifelong if LVEF <40%
ACE inhibitor / ARBBlocks RAAS-driven remodelingEspecially with LV dysfunction, HF, diabetes, or CKD
Aldosterone antagonistPost-MI with LVEF <40% plus HF or diabetesWatch potassium and renal function
Sublingual NTGPRN for breakthrough anginaEvery patient goes home with it
Discharge checklist mnemonic

A-B-C-D-E:Aspirin + ACE inhibitor · Beta blocker · Clopidogrel (or other P2Y₁₂) + Cholesterol (high-intensity statin) · Diet and Diabetes control · Exercise / cardiac rehab. Add smoking cessation to every one of these.

Complications of MI

Don't skip the depression point

Many ACS patients develop depression while recovering. It's listed in the complications for a reason. On rotations, a patient who "isn't taking their meds" after an MI is often depressed rather than noncompliant.

Monitoring

ParameterWhenWatching for
Continuous multilead ECGThroughout admissionArrhythmias, ongoing or recurrent ischemia
Serial troponinPresentation, 3–6 h, beyond 6 h if high risk with normal valuesDynamic rise/fall ≥20% confirms acute injury
Vital signsFrequentlyHypotension limiting beta blocker, ACEi, nitrate titration
Renal functionBaseline and during admissionDrives anticoagulant dosing; contrast nephropathy after PCI
Potassium and magnesiumBaseline and periodicallyArrhythmia risk
CBC, aPTT/anti-Xa, INRBaseline and during antithrombotic therapyBleeding, HIT
Lipid panelFasting, on admissionConfirms high-intensity statin need
LVEF (echo)Before or shortly after dischargeDetermines beta blocker duration, ACEi and MRA indication, ICD candidacy

Patient Counseling

  • Never stop the P2Y₁₂ inhibitor early on your own.If a stent was placed, stopping DAPT prematurely can cause stent thrombosis, which is often fatal. Any provider or dentist who wants it held must talk to cardiology first. This is the single most important thing to say.
  • Sublingual nitroglycerin technique:sit down first (it can drop your BP). One tablet under the tongue, wait 5 minutes. If pain persists, call 911, then may take up to 3 doses total 5 minutes apart. Keep it in the original amber glass bottle, not a pill organizer - light and moisture destroy it. Replace every 6 months after opening.
  • No sildenafil, tadalafil, or vardenafilwith nitrates. Ask directly and non-judgmentally; patients often won't volunteer it.
  • Symptoms to return for:chest pain lasting more than a few minutes, pain radiating to arm/jaw/back, shortness of breath, sweating, nausea. Emphasize that a repeat event may feel different from the first one.
  • Bleeding on DAPT:report black tarry stools, blood in urine, coughing or vomiting blood, prolonged nosebleeds, unusual bruising, or any head injury.
  • Ticagrelor dyspneais common, usually mild and transient, and is not heart failure. Warn them so they don't stop the drug.
  • Cardiac rehabimproves survival and quality of life. Push it actively - enrollment rates are terrible.
  • Smoking cessationis the single highest-yield lifestyle change after an MI.
  • Mood check.Depression after a heart attack is common and treatable. Tell them upfront so they'll mention it.

High-Yield Recall Sheet

  • ECG within 10 minutes.Don't wait for troponin in STEMI.
  • STEMI= ST elevation ≥1 mm in 2 contiguous leads, or new LBBB, + troponin.
  • NSTEMI vs UA:troponin is the only difference.
  • Troponinrises 2–4 h, stays up to 2 weeks, acute = ≥20% dynamic change.
  • Primary PCI within 90 minof first medical contact; 120 minif transfer required.
  • Fibrinolysis if PCI >120 min away, given within 30 min of arrival.
  • Aspirin 162–325 mg chewed, then 81 mg indefinitely.
  • Clopidogrel 600 mg before PCI, 300 mg with fibrinolysis, NO load if age ≥75.
  • Clopidogrel is the P2Y₁₂ of choice with fibrinolysis(only one with large-trial data).
  • Oxygen only if SaO₂ <90%- routine oxygen may cause harm.
  • Nitrates contraindicated with PDE-5 inhibitors.
  • Beta blocker orally within 24 h, continue ≥3 years (lifelong if EF <40%).
  • Non-DHP CCBsonly if beta blocker contraindicated AND no LV dysfunction, shock risk, or AV block.
  • Absolute fibrinolysis contraindications:any prior hemorrhagic stroke, ischemic stroke <3 mo, intracranial neoplasm/AVM, active bleeding, aortic dissection, head trauma <3 mo, intracranial surgery <2 mo, severe uncontrolled HTN.
  • ICH risk with fibrinolysis ~1%.
  • Fondaparinux= ischemia-guided NSTE-ACS only, not standalone during PCI.
  • Discharge bundle:aspirin + P2Y₁₂ + high-intensity statin + beta blocker + ACEi/ARB (± MRA if EF <40%) + SL NTG.
  • 90% of MIs are Type 1(plaque rupture). Type 2 = supply/demand mismatch, treat the underlying cause.
  • Plaques that rupture are usually <70% occlusive- which is why many patients had no prior angina.