Antianginal Therapy

Snapshot

A 50-year-old man presents to the emergency department after experiencing chest pain. He describes the pain as pressure-like that affects the sternum and radiates down the left arm. Medical history is significant for hypertension, hypercholesterolemia, and type II diabetes. He smokes 1 pack of cigarettes per day for the past 20 years. On physical exam, the patient appears anxious and diaphoretic. An electrocardiogram demonstrates an ST-segment elevation in leads V1 and V2. Cardiac troponins are sent. He is given aspirin, nitroglycerin, metoprolol, clopidogrel, and unfractionated heparin. The cardiac catheterization lab is activated and the cardiologist is consulted.

Introduction

Appropriate treatment for acute coronary syndrome must be instituted immediately in order to

• limit myocardial damage
  • decrease the risk of complications
  • restore the balance between myocardial oxygen supply and demand

NSTEMI and Unstable Angina (UA)

Introduction

NSTEMI and UA are managed in the same manner

the goal is to to provide 

• anti-ischemic therapy

  restores the myocardial oxygen supply and demand

• anti-thrombotic therapy

  prevents further growth of the partial thrombotic occlusion

Medications

• anti-ischemic therapy
  • β-blockers (e.g., metoprolol)
    • mechanism
      • decreased sympathetic drive to the heart
        • promotes myocardial electrical stability
        • decreases myocardial demand
        • ↓ cAMP 
      • improves mortality in patients with an MI
    • contraindications
      • bronchospasm
      • decompensated heart failure
      • hypotension
  • nitrates (e.g., nitroglycerin, isosorbide mononitrate, and dinitrate)  
    • mechanism
      • venodilation reduces preload to the heart, which reduces myocardial demand
        • recall that a reduction in preload reduces ventricular wall stress
      • coronary artery dilation improves blood flow to the myocardium
        • recall that venodilation >> arterial dilation 
      • ↑ cGMP 
      • arginine is a biochemical precursor of nitric oxide, and supplementation of this amino acid may have a role in augmenting the treatment regimen for chronic stable angina patients   
      • contraindicated in patients taking vasodilatory medication for erectile dysfunction (e.g., sildenafil)   
    • adverse events
      • nitroprusside causes cyanide toxicity 
      • development of tolerance for the vasodilating action during the work week 
      • a headache may result from vasodilation of cerebral arteries  
  • calcium channel blockers (e.g., verapamil and diltiazem)
    • mechanism
      • reduces heart rate and cardiac contractility
      • this medication is reserved for patients unresponsive to β-blockers and nitrates or have contraindications to β-blockers
        • this is because calcium channel blockers do not provide a mortality benefit
  • anti-thrombotic therapy
    • aspirin
      • mechanism
        • an inhibitor of thromboxane A2 synthesis 
          • thromboxane A2 is a prominent promoter of platelet activation
        • improves mortality and should be continued indefinitely
    •  P2Y12 ADP receptor inhibitor (e.g., clopidogrel and ticagrelor)
      • mechanism
        • prevents ADP from binding to the P2Y12 receptor, which would normally further activate platelets
  • anti-coagulation therapy
    • unfractionated heparin
      • mechanism
        • binds to antithrombin to enhance its effects
        • inhibits factor Xa

ST-Segment Elevation Myocardial Infarction (STEMI)

Introduction

• STEMI suggest that there is a total occlusion of the vessel
  • thus the main goal is to induce rapid reperfusion via
    • percutaneous coronary intervention (PCI) OR
    • fibrinolytic therapy
  • patients are also given medications such as those used in NSTEMI and UA
    • aspirin
    • unfractionated heparin
    • β-blockers
    • nitrates
    • P2Y12 ADP receptor inhibitor 
• Reperfusion therapy
  • primary PCI 
    • the preferred method for reperfusion
    • must be performed within 90 minutes of first medical contact
      • aspirin and a P2Y12 receptor inhibitor is given prior to the procedure
  • fibrinolytic therapy (e.g., alteplase)
    • performed if PCI cannot be performed within 90 minutes or is unavailable
    • fibrinolytics convert plasminogen to plasmin, which degrades newly formed clots

Adjunctive Therapy

• Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril)
  • provides a mortality benefit
  • prevents ventricular cardiac remodeling and reduces the rate of heart failure
• Statins (e.g., atorvastatin) 
• an HMG-CoA reductase inhibitor that lowers cholesterol levels