Academic Day Seminars

ADS – Acute Coronary Syndrome

Types of MIs:

  1. Spontaneous MI
  2. MI 2ry to an ischemic imbalance
  3. MI resulting in death when biomarker values are unavailable
  4. a) MI related to percutaneous coronary intervention (PCI)

4. b) MI related to stent thrombosis

5. MI related to coronary artery bypass grafting (CABG)

Pathophysiology:

  1. Plaque rupture
  2. Dynamic obstruction
    • Coronary spasm, vasoconstriction
  3. Progressive mechanical obstruction
    • Atherosclerosis, restenosis post-PCI
  4. ↑ Myocardial O2 demand –> ↑ HR, ↓ BP, anemia

Complications:

  • Cardiogenic shock
  • Heart failure
  • Valvular dysfunction
  • Atrial and/or ventricular tachyarrhythmias
  • Bradycardia
  • Heart block
  • Pericarditis
  • Stroke (thrombus embolization)
  • Venous thromboembolism
  • Left ventricular free- wall rupture
  • Mortality

Diagnosis:

NSTE- and STE-ACS identified by: symptoms, ECG findings, biomarkers for myocardial injury and necrosis (must have 2/3 of above criteria)

  • Usually the symptoms and ECG are the most timely to get (as opposed to biomarkers)
  UA NSTEMI STEMI
Symptoms Chest pain ≥ 20 mins Chest pain ≥ 20 mins Chest pain ≥ 20 mins
Cardiomyocyte Damage Ischemia; no damage Infarction; non- transmural damage Infarction; transmural damage
ECG Normal ST depression, T wave inversion, transient ST elevation, non-specific changes ST elevation ≥ 2 contiguous leads, new LBBB
Troponins Normal Elevated Elevated

Risk stratifying tools:

TIMI GRACE
  • NSTE-ACS only
  • Predicts 30 day and 1 year mortality
  • Validated
  • Doesn’t include heart failure
  • Simple integer-based scoring system, easily done at bedside
  • Both STE-ACS and NSTE-ACS
  • Predicts in hospital and 6 month mortality
  • Validated
  • Includes heart failure and renal function
  • Requires calculating too

Morphine/Analgesics:

Indication Pain not immediately relieved by nitrates, anxiety, pulmonary edema
MOA/Benefits Alleviates work of breathing, reduces anxiety, and favourably affects ventricular loading conditions ↓’d preload ↓ myocardial oxygen demand
Dose/ Administration IV morphine sulfate 4-8 mg initially, with increments of 2-8 mg IV at 5- to 15-minute intervals PRN
Avoid/Caution Lethargic
Hypotension
Respiratory depression
Nausea and vomiting
Contraindicated in patients with R ventricular infarction (b/c they’re so dependent on preload)
Tips Naloxone 0.1-0.2 mg IV q15 when indicated to reverse Atropine 0.5-1.5 mg IV for morphine-related bradycardia

Oxygen

Indication Hypoxemia (O2 sat <90%), HF, dyspnea
MOA Oxygen supplementation
Benefits Benefits on myocardial damage or reducing morbidity/mortality not known
May limit ischemic myocardial injury
Dose/ Administration 2-4 L/minute via nasal prongs
Avoid/Caution Meta Analysis 3x ↑ risk of death vs room air COPD and CO2 retention

Nitrates

Indication Ongoing chest pain, HTN, and HF
MOA ↓’s preload and afterload through peripheral arterial and venous dilation
Relaxes epicardial coronary arteries ↑ coronary flow Dilation of collateral vessels
Benefits Ameliorates signs/symptoms of MI
Does not attenuate myocardial injury unless vasospasm plays a significant role
Dose/ Administration 0.4 mg SL every 5 minutes x 3 doses
Avoid/Caution Suspected R Ventricular infarction
Sys BP<90 or >30 below baseline Recent (24-48 hours) 5’-PDE inhibitors

Aspirin

Indication ALL patients without contraindication
MOA At doses >162 mg, rapid antithrombotic effect caused by inhibition of thromboxane A2 production
Benefits ISIS-2: ASA effective alone for treatment of evolving acute MI
• ↓ 35 day mortality (ARR 2.4%, NNT = 42/35 days)
Dose/ Administration 160-325 mg po chewed x 1, then 75-325 mg po daily
Avoid/Caution Allergy

Antiplatelets in STEMIs:

Drug Initial Dose Maintenance Dose Duration COR
ASA 165-325 mg chewed 81-325 mg po daily Indefinitely I
Thienopyridines to support reperfusion with fibrinolytic therapy  
Clopidogrel ≤75 y: 300 mg po >75 y: 75 mg 75 mg po daily At least 14 days and up to 1 yr I
Thienopyridines to support reperfusion with PCI  
Clopidogrel 600 mg po 75 mg po daily 1 year I
Ticagrelor 180 mg po 90 mg po BID
Prasugrel 60 mg po 10 mg po daily

 

Drug Initial Dose Maintenance Dose Duration COR
GP IIb/IIIa receptor antagonists with UFH/bivalirudin to support reperfusion with PCI
Abciximab 0.25 mg/kg IV bolus 0.125 mcg/kg/min (max 10 mcg/min) 12 hours IIa
Tirofiban 25 mcg/kg IV bolus 0.15 mcg/kg/min CrCl<30mL/min: • ↓ inf. by 50%

 

18-24 hours
Eptifibatide

(double bolus)

180 mcg/kg IV bolus, then
180 mcg/kg IV bolus 10 min later 2 mcg/kg/min CrCl<50 mL/min:

•      ↓ inf. by 50%

•      Avoid in HD

 

12-24 hours
Pre-cath lab IV GPIIb/IIIa administration
Intracoronary abciximab 0.25 mg/kg bolus     IIb

Anticoagulants in STEMIs:

Adjunct Dose Duration  
UFH Primary PCI – weight-based IV bolus to achieve therapeutic ACT Until PCI complete  
Fibrinolysis –
Weight-based IV bolus and infusion adjusted to obtain aPTT of 1.5-2.0 times control

 

48 hrs or until revascularization  
Enoxaparin Age <75y – 30-mg IV bolus, followed in 15 min by 1 mg/kg SC q12h (max 100 mg for 1st two doses)
Age ≥75 y – no bolus, 0.75 mg/kg sc q12h (max 75 mg for 1st two doses)

CrCl <30 ml/min – 1 mg/kg sc q24h

 

Index hospitalization, up to 8 d or until revascularization  
Fondaparinux 2.5 mg IV, then 2.5 mg sc daily starting the following day CrCl <30 ml/min – contraindicated
Not recommended as sole anticoagulant in patients with PCI

 

Index hospitalization, up to 8 d or until revascularization  
Bivalirudin Only PCI 0.75 mg/kg IV bolus, then 1.75 mg/kg/h infusion with or without prior treatment with UFH (may give additional 0.3 mg/kg bolus) CrCl <30 ml/min – ↓ infusion to 1 mg/kg/h Until PCI complete

Early management of ACS

  • Beta-blockers:
    • ↓ myocardial oxygen consumption alleviates ischemic symptoms
    • Mortality benefits seen in setting of Heart Failure
      • Metoprolol succinate SR (MERIT-HF)
      • Carvedilol (COPERNICUS)
      • Bisoprolol (CIBIS-II)
    • The benefit of PO BB are mostly seen in the older studies (e.g. the pre-reperfusion era) – this benefit is not seen as much so in the reperfusion era.
    • Contemporary practice of treatment of MI, B-blockers have: Ø no mortality benefit (all-cause or CV), ↓ recurrent MI and angina (short-term), at the expense of ↑ heart failure, cardiogenic shock, and drug discontinuation

    • Guidelines:1. Initiate oral beta blockers within the first 24 h in the absence of HF, low-output state, risk for cardiogenic shock, or other contraindications to beta blockade

      2. Use of sustained-release metoprolol succinate, carvedilol, or bisoprolol is recommended for beta-blocker therapy with concomitant NSTE-ACS, stabilized HF, and reduced systolic function

      3. Re-evaluate to determine subsequent eligibility in patients with initial contraindications to beta blockers

  • ACE inhibitors: prevent infarct growth and reduce ventricular remodeling
    • Mortality benefit seen in heart failure pts post-MI: captopril (SAVE), ramipril (AIRE), trandolapril (TRACE), lisinopril (GISSI-3)
    • Recommended: LVEF ≤ 40%, diabetes, anterior MI, or hypertension
    • Unless contraindicated: Hypersensitivity (including angioedema), combined use with aliskerin in diabetic patients, Pregnant/breastfeeding, Bilateral renal artery stenosis or unilateral artery stenosis in patients with a solitary kidney
  • Calcium channel blockers: dec myocardial O2 demand through coronary vasodilation, neg inotropy and chronotropy
    • Consider calcium channel blockers and nitrates in vasospastic angina (IIa)
      • Avoid beta blockers
    • Unless contraindicated:
      • Hypersensitivity, SBP < 90 mmHg
      • Non-DHP:
        • LV dysfunction, 2nd or 3rd degree AV block
        • Concurrent use of IV route with IV beta blockers
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