Karimi ACD

Define Acute Coronary Syndrome (ACS) and Myocardial Infarction (MI)

• Acs is an umbrella term for acute clinical manifestations including unstable angina (UA), non-ST-segment evaluation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction 

  • If unstable angina not treated → often progresses to NSTEMI or STEMI

• Unstable angina is the most severe form of angina with increasing intensity, frequency, and duration

  • A combination of of atherosclerotic plaque formation, platelet aggregation (clot formation), and vasospasm 

  • Usually an immediate precursor to MI

• MI (heart attack): occurs when ischemia block blood flow entirely, causing that affected cardiomyocytes to slow down and eventually die, leading to the formation of irreplaceable scar tissue

Serum Protein Elevations During MI ?

• Troponin T and I

  • Troponin unique to heart muscle

• Creatine Kinase Myocardial Brand (CK-MB)

  • Semi-specific 

• Myoglobin 

  • Non-specific

• Troponins play an important role in the MI detection as they are part of the contractile apparatus of cardiomyocytes and are released into the circulation upon a myocardial injury

  • Troponin levels peak = 36 hours after an infarct and may remain high for 7 -10 days 

Define MI’s two major types: ST-Segment Elevation (STEMI) and Non-ST-Segment Elevation (NSTEMI)

• NSTEMI: a partial thickness (subendocardial) infarct caused by the occlusion of a coronary artery, resulting a partial necrosis of the left ventricular wall (⅓ to ½ of left ventricular wall)

• STEMI: a full thickness (transmural) infarct caused by complete occlusion of blood vessel lumen, resulting in necrosis completely through the left ventricular wall 

Know the risk factors for ACS

• Risk factors for ACS are the same as those that cause CAD/CCD since ACS is the acute progression of plaque buildup and rupture 

Describe the pathophysiology of ACS including unstable angina (UA), STEMI and NSTEMI

• UA: the plaque ruptures and a thrombus forms, causing partial occlusion. This is a "supply ischemia” without true infarct

• NSTEMI: the ruptured plaque thrombus causes a partial occlusion that is severe enough to result in injury and subendocardial infarct

• STEMI: complete occlusion of the blood vessels lumen result in a transmural infarct and injury to myocardium

Recall the characteristic biomarker and ECG differences between UA, STEMI and NSTEMI

• UA: Normal tropons. ECG may be normal, show inverted T waves, or ST depression

• NSTEMI: Elevated troponins, ECG is similar to UA (normal, inverted I waves, ST depression)

• STEMI: elevated troponins. ECG shows hyperacute T waves or ST elevation (not cardiac troponins peak about 36 hours after infarct)

Aspirin

• irreversibly inhibits COX-1, which decreases thromboxane A2 (TXA2) and prevents platelet aggregation

  • Gives aspirin antiplatelet effect that may be useful for patients at high risk for CV disease

  • DOA of antiplatelet effect: 7-10 days

    • Other tissue 6-12 hrs

  • Avoid normal aspirin dose in children due to link to Reye’s syndrome

P2Y12 inhibitors

• inhibit the ADP receptor to decrease platelet aggregation 

  • Agents:

    • Clopidogrel (Plavix)

      • Both prodrug and irreversible inhibitor of P2Y12 and thereby inhibits ADP-mediated platelet aggregation

      • Slow offset of actions (return to baseline after 5 days)

      • DI: proton pump inhibitor may reduce its effectiveness due to inhibition of CYP2C19 

      • ADE: increase risk of bleeding 

    • Prasugrel

      • Produrg but activated by hydrolysis in liver

      • Activation not as variable as clopidogrel, and activated mor efficiently then clop., having a faster onset of action

      • ADE: Bleeding, more than Clopidogrel

      • CI: pt with hx of stroke due to bleeding risk 

    • Ticagrelor

      • More rapid onset and offset than clopidogrel

      • Also causes greater and more predictable inhibition of platelet aggregation

      • Metabolized in liver via CYP 3A4 and thus has interactions with potent 3A4 inhibitors or inducers 

      • ADE: Bleeding, dyspnea reported in 17% of patients

    • Cangrelor (only IV)

  • Stronger platelet inhibition than aspirin

  • ADE: Bleeding 

Gllb/llla inhibitors

• IV biologic agents that inhibits Gllb/llla receptors to decrease  aggregation 

  • Agents

    • Abiximab

      • Has a long DOA (24 hr after infusion)

    • Tirofiban

    • Eptifibatide

  • ADE: bleeding 

    • Less common: thrombocytopenia 

Anticoagulants

Inhibit the coagulation cascade by activating antithrombin III, which inhibits factor Xa, ultimately decreasing fibrin formation and clot formation 

• Agents

  • Unfractionated 

  • Heparin 

  • Enoxaparin

• Admin: parenterally 

• ADE: Bleeding (common), Thrombocytopenia (less common)

Fibrinolytics (Tissue Plasminogen Activators): Enzymes that mimic native native tissue plasminogen activator. They increase the formation of plasmin, which directly degrades fibrin and fibrinogen to restore blood flow

• Agents:

  • Alteplase

  • Tenecteplase

  • Reteplase 

• ADE: Bleeding 

Describe why agents such as ACE-Inhibitors, Statins, nitroglycerin, and beta blockers are useful in ACS

• Statins: all patients with UA, STEMI or NSTEMI should be discharged on an intensive statin (atorvastatin 40-80 mg/day), unless contraindicated or patients > 75 years receive a moderate-intensity statine (due to AE)
  

• ACEi/ARBs: treatment with an ACEi is recommended in all patients with MI, if intolerable use ARB
  

• Nitroglycerin: short-acting (sublingual tablets or spray) or long-acting if vasospasms  

• Beta-Blockers: reduce oxygen demand (by lowering heart rate, contractility, and blood pressure), which helps relieve anxiety and reduce pain. Less oxygen demand means less anaerobic oxidation, reducing lactic acid formation