II. History

  1. Willow bark contains Salicin (Salicylic acid)
    1. Used in folk medicine for mild pain and fever
  2. Acetylsalicylic Acid is a derivative of salicylic acid
    1. Synthesized in 1853 by the Bayer brothers

III. Indications

  1. Analgesia in rheumatic conditions
    1. Other agents including NSAIDs are preferred for analgesia
  2. Prevention of coronary and cerebrovascular events
    1. See Cardiac Risk Management
    2. Mainstay of secondary and tertiary cardiovascular prevention
    3. Has fallen out of favor for primary cardiovascular disease prevention aside from high risk patients age 40 to 60 years
      1. See decision aid in resources below

IV. Contraindications

  1. Children with viral illness (Varicella, Influenza)
    1. Risk of Reye's Syndrome (FDA Black Box Warning)
  2. Gout
  3. Hypersensitivity to Aspirin
  4. Active Peptic Ulcer Disease

V. Mechanism

  1. Aspirin irreversibly inactivates cyclooxygenase (COX)
    1. Blocks Thromboxane and Prostaglandin synthesis
    2. Contrast with NSAIDS which reversibly block COX
  2. Platelet Effects (Thromboxane-related)
    1. Inhibits Platelet aggregation via cyclooxygenase blockade of Thromboxane A2 synthesis
    2. Aspirin Irreversibly poisons Platelets for their remaining life (8-10 days)
    3. New Platelets are generated at a rate of 10% per day (25,000/day for a patient with a 250,000 Platelet Count)
      1. By 2 days off Aspirin, a patient will have 50,000 normal Platelets (enough to counter bleeding)
      2. By 7 days off Aspirin, a patient will have 70% or 175,000 normal Platelets (typical level required for elective surgery)
      3. By 10 days off Aspirin, a patient will have 100%normal Platelets (level required by some clinicians for major surgery)
  3. NSAID effects (Prostaglandin-related)
    1. Antipyretic (Lowers Temperature)
    2. Antiinflammatory effect
      1. Inhibits Prostaglandin biosynthesis at higher dose
    3. Analgesic effect
      1. Relieves pain of mild to moderate intensity at low dose

VI. Medications: Regular Release Aspirin

  1. Strengths
    1. Low dose (baby ASA): 81 mg (range 75 to 100 mg)
    2. Higher dose: 325 mg (range 200 to 325 mg)
  2. Formulations
    1. Immediate release tablets
    2. Enteric coated
    3. Buffered
  3. Combinations (examples)
    1. Aspirin with Dipyridamole (Aggrenox)
    2. Aspirin with Acetaminophen and Caffeine (Excedrin Migraine)

VII. Medications: Extended Release Aspirin

  1. Durlaza ( Extended-release Aspirin)
    1. No evidence that extended release Aspirin ($6/pill) has advantages over Aspirin 81 mg ($0.01/pill)
    2. (2015) Presc Lett 22(12): 71
  2. Vazalore (liquid-filled Aspirin capsule)
    1. Designed for delayed absorption to Small Intestine, postulated to reduce Gastrointestinal Bleeding
    2. No evidence that Vazalore reduces longterm Gastrointestinal Bleeding risk
    3. Expensive ($1 per capsule, compaired with $0.01/pill of standard Aspirin)
    4. (2021) Presc Lett 28(11): 62

VIII. Dosing

  1. Use lowest appropriate dose (reduces adverse effects)
  2. Anti-Platelet action
    1. General
      1. Do not exceed 81 to 160 mg daily if on Coumadin
    2. Coronary Artery Disease
      1. See Cardiovascular Disease-related Antiplatelet Use
      2. Immediate Myocardial Infarction Management: 325 mg
      3. Primary coronary disease prevention: 81 mg orally daily
        1. As of 2018, Aspirin is no longer recommended for primary prevention in most patients
      4. Tertiary prevention (post-MI)
        1. Aspirin 81 mg orally daily
          1. Similar efficacy in coronary disease prevention as the 325 mg dose
          2. Half the risk of gastrointestinal Hemorrhage as the 325 mg dose
        2. References
          1. Eikelboom (2012) Chest 141(2 Suppl):e89S-119S [PubMed]
    3. Cerebrovascular Accident
      1. See Antiplatelet Therapy in CVA and TIA
      2. Prevention in known vascular disease: 81 to 325 mg orally daily
      3. OConnor (2001) Am J Cardiol 88:541-6 [PubMed]
  3. Antipyretic or Analgesic Dose
    1. Adult: 600 mg PO q4 hours
    2. Adult: 650-1000 mg PO q4-6 hours
  4. Antiinflammatory dose
    1. Adult: 4 grams maximum per day

IX. Management: Reversal

  1. Platelet Transfusion 1 unit (6 pack)
  2. Consider Desmopressin (DDAVP) 0.3 mcg/kg (expert opinion)
  3. Consider Recombinant activated Clotting Factor VII (rFVIIa) 30-90 mcg/kg (expert opinion)

X. Pharmacokinetics

  1. Aspirin is rapidly absorbed in the upper Small Intestine
  2. Hepatic metabolism

XI. Drug Interactions

  1. Ibuprofen inactivates Aspirin Anticoagulation effect
    1. Competes for same receptors
    2. Naprosyn and Indocin do not do this
    3. Avoid NSAIDS in patients on prophylactic Aspirin for cardiovascular indications

XII. Adverse Effects

  1. Gastrointestinal Effects
    1. Gastrointestinal intolerance
    2. Peptic Ulcer Disease (Erosive Gastritis)
      1. Aspirin higher risk for Peptic Ulcer Disease
      2. Other Salicylates have lower risk than most NSAIDs
    3. Gastrointestinal Bleeding
      1. Middle aged: 2-4 per 1000 on Aspirin 5 years
      2. Older patient: 4-12 per 1000 on Aspirin for 5 years
      3. Roderick (1993) Br J Clin Pharmacol 35:219-26 [PubMed]
  2. Central Nervous System Effects: Salicylism
    1. Tinnitus
    2. Decreased Hearing acuity
    3. Vertigo
  3. Central Respiratory effects
    1. Very high dose: Hyperpnea
    2. Lethal doses: Respiratory depression or apnea
  4. Miscellaneous Effects
    1. Serum Uric Acid changes
      1. Aspirin <2 g/day: increases serum Uric Acid
      2. Aspirin >4 g/day: lowers serum Uric Acid <2.5 mg/dl
    2. Asymptomatic hepatitis
    3. Exacerbation of Renal Insufficiency
    4. Hypersensitivity Reaction (Aspirin Allergy)
      1. Associated with Nasal Polyps and Asthma

XIII. Safety

  1. Pregnancy Category D in third trimester (Category C in first and second trimesters)
  2. Lactation
    1. Low dose Aspirin (75 to 325 mg/day) results in minimal to no Aspirin in Breastmilk
    2. High dose Aspirin is excreted in Breast Milk and is not recommended (risks include Reye's Syndrome)
    3. LactMed Database
      1. https://www.ncbi.nlm.nih.gov/books/NBK501196/

XIV. Efficacy

  1. Safer and lower cost than many NSAIDs
    1. Aspirin is an underused medication
  2. Coronary disease prevention
    1. Falling out of favor in the primary prevention of lower risk patients without Myocardial Infarction or stroke
      1. Number Needed to Treat: 1 in 250 to prevent one first cardiovascular event (primary prevention)
      2. Aspirin is still an important mainstay of secondary prevention (known cardiovascular disease)
      3. Aspirin is still considered beneficial for primary prevention when 10 year CVD risk >10% in age 40 to 60 years
      4. Aspirin risk may outweigh benefit over age 75 years (consider discontinuing Aspirin in advanced age)
    2. Benefits may not outweigh the risks of GI Bleeding, Hemorrhagic CVA
      1. Number Needed to Harm: 1 in 200 to result in major bleeding
      2. Hemorrhage risk increases with older age, male gender, Tobacco Abuse, NSAID and Anticoagulant use
    3. References
      1. Davidson (2022) JAMA 327(16):1577-84 [PubMed]
  3. Other benefits
    1. May reduce Colorectal Cancer risk (NNT 77)

XVI. References

  1. McCarty (1972) Arthritis and Allied Conditions
  2. Katzung (1989) Basic and Clinical Pharmacology
  3. (2000) Med Lett Drugs Ther 42(1085):73-8 [PubMed]

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aspirin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
ASPIRIN 325 MG TABLET Generic OTC $0.01 each
ASPIRIN EC 325 MG TABLET Generic OTC $0.02 each
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asa (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
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