Antiplatelet Therapy for Vascular Disease

Aka: Antiplatelet Therapy for Vascular Disease, Antiplatelet Therapy, Cardiovascular Disease-related Antiplatelet Use, Dual Antiplatelet Therapy, DAPT for Coronary Artery Disease

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II. Management: Guidelines

  1. Aspirin or Clopidogrel
    1. Aspirin 81 mg dose appears sufficient in most cases
      1. Post-CABG, Aspirin 325 mg daily may be used for the first year
      2. Initial dosing in Myocardial Infarction is 324 mg
    2. Cerebrovascular Disease
      1. See Antiplatelet Therapy in CVA and TIA
      2. Initial Transient Ischemic Attack (TIA)
      3. Initial Ischemic Cerebrovascular Accident (CVA)
    3. Cardiovascular Disease
      1. Chronic Stable Angina
      2. Peripheral Arterial Disease
  2. Aspirin 81 mg and Clopidogrel 75 mg (or Ticagrelor 90 mg twice daily, Prasugrel 10 mg daily)
    1. See Antiplatelet Therapy in CVA and TIA
    2. ST Segment elevation Acute Coronary Syndrome
    3. Recurrent Acute Coronary Syndrome
    4. Post-coronary stenting (with Clopidogrel duration based on type of stent)
    5. Established cardiovascular disease (or high risk) without indication for coronary stenting
      1. Dual therapy lowers MI and CVA risk but does not lower mortality and does increase bleeding risk
      2. Indications and duration per local expert opinion (consult cardiology)
      3. Squizzato (2017) Cochrane Database Syst Rev (12):CD005158 +PMID:29240976 [PubMed]
  3. Aspirin and Extended release Dipyridamole
    1. See Antiplatelet Therapy in CVA and TIA
    2. Recurrent Transient Ischemic Attack (TIA)
    3. Recurrent Ischemic Cerebrovascular Accident (CVA)
  4. Aspirin, Clopidogrel and Anticoagulant (Warfarin or DOAC)
    1. Triple antithrombotic therapy may at times be indicated
      1. Baseline Atrial Fibrillation or Mechanical Heart Valve with recent coronary stent placement
    2. Avoid triple antithrombotic therapy if at all possible (high bleeding risk)
      1. Serious bleeding in 2% within the first month and 12% in the first year
      2. In some cases Direct Oral Anticoagulants (DOACs, esp. Eliquis) are used in place of Warfarin
      3. In stable heart disease, triple therapy for 3 months after bare stent and 6 months after DES
        1. Then Anticoagulant and Clopidogrel for up to 12 months total
        2. Then Aspirin or Clopidogrel longterm
      4. (2017) Presc Lett 24(4): 22
    3. Often Aspirin may be discontinued while on Clopidogrel and Anticoagulant (Warfarin or DOAC)
      1. Consider triple therapy with Aspirin for first month after stenting, then stop Aspirin
      2. Dual therapy has half of the bleeding risk of triple therapy without significant increased CAD event risk
      3. Consider in those after elective coronary stent placement or multiple bleeding risks
      4. Aspirin may then be restarted when Clopidogrel is discontinued
      5. (2019) Presc Lett 26(5)
      6. Dewilde (2013) Lancet 381(9872): 1107-15 [PubMed]

III. Protocol: Durations of post-coronary stenting Dual Antiplatelet Therapy (e.g. Aspirin 81 AND Clopidogrel)

  1. Duration: 1 month of Dual Antiplatelet Therapy (DAPT)
    1. Bare metal stent
  2. Duration: 3 months of Dual Antiplatelet Therapy (DAPT), followed by 9 months of Clopidogrel (or Ticagrelor) alone, then Aspirin alone
    1. HIgh risk of bleeding (e.g. Gastrointestinal Bleeding, Intracranial Bleeding, advanced age) AND
    2. Stable Ischemic Heart Disease after Drug-eluting Stent
  3. Duration: 6 months of Dual Antiplatelet Therapy (DAPT), then Aspirin daily
    1. Standard duration of DAPT for Stable Ischemic Heart Disease after Drug-eluting Stent (as of 2016)
    2. Follow with 6 months of Clopidogrel (or Ticagrelor) alone, then Aspirin alone
  4. Duration: 12 months of Dual Antiplatelet Therapy (DAPT), then Aspirin daily
    1. Acute Coronary Syndrome event (regardless of stenting)
  5. Duration: 18 months of Dual Antiplatelet Therapy (DAPT), then Aspirin daily
    1. DAPT Score (Dual-Antiplatelet Therapy Decision Rule) of 2 or greater
  6. References
    1. (2022) Presc Lett 29(2): 12
    2. Levine (2016) J Am Coll Cardiol +PMID:27036918 [PubMed]
    3. Yeh (2016) JAMA 315(16):1735-9 [PubMed]

IV. Protocol: Post-Myocardial Infarction

  1. Aspirin 81 mg orally daily indefinitely
  2. Platelet ADP Receptor Antagonist (e.g. Clopidogrel or Plavix) added to Aspirin routinely following ST Elevation MI
    1. Platelet ADP Receptor Antagonist options (Ticagrelor, Prasugrel, Clopidogrel)
    2. Duration following ST Elevation MI (typically 12 months)
      1. See Platelet ADP Receptor Antagonist (e.g. Clopidogrel)
      2. Continue for at least 14 days and consider one year of therapy in all post-STEMI cases
    3. Stenting-related durations
      1. Bare metal stents require minimum of 1 month of Platelet ADP Receptor Antagonist (e.g. Clopidogrel)
      2. Drug-eluting Stents require minimum of >6-12 months (depending on stent-type)
        1. See Angioplasty
        2. Possible benefit of Ticagrelor, Prasugrel over Clopidogrel, but at higher bleeding risk and 30x cost
          1. Rezaei (2017) Int J Cardiol 235:61-66 [PubMed]
        3. However, Clopidogrel may offer similar efficacy after the first week post-stenting
          1. Sibbing (2017) Lancet 390(10104):1747-57 [PubMed]

V. Precautions: Perioperative Stent Implications

  1. See Angioplasty
  2. Balloon Angioplasty
    1. Time since surgery <14 days: Delay non-urgent or elective surgery
    2. Time since surgery >14 days: Proceed to surgery with Aspirin
  3. Bare-Metal Stent
    1. Time since surgery <30-45 days: Delay non-urgent or elective surgery
    2. Time since surgery >45-90 days: Proceed to surgery with Aspirin
  4. Drug-eluting Stent
    1. Time since surgery <365 days: Delay non-urgent or elective surgery
    2. Time since surgery >365 days: Proceed to surgery with Aspirin
  5. Minimum dual antiplatelet time for stents
    1. Dual Antiplatelet Therapy should be continued for one year with all drug eluting stents
      1. Deviation from the one year minimum is for serious extenuating circumstances
      2. All deviations from the one year minimum should be discussed with cardiology
    2. Balloon Angioplasty: >2 weeks
    3. Bare metal stents: >1 month
    4. Sirolimus (Rapamune) eluting stents: >3 months
    5. All other Drug-eluting Stents: >6-12 months

VI. Management: Gastrointestinal Prophylaxis

  1. Proton Pump Inhibitors are often used for Peptic Ulcer prevention while on combined anti-Platelet agents
    1. Ranitidine has been used more commonly for GI prophylaxis
    2. Potential Cytochrome P450 2C19 Drug Interaction with Proton Pump Inhibitors
  2. Cytochrome P450 2C19 Drug Interaction with Proton Pump Inhibitors
    1. Potential to predispose to more post-stenting events
    2. Cogent study (see Bhatt below) left open that this interaction may be important
    3. Studies have not observed an increase in number of cardiovascular events
      1. Ho (2009) JAMA 301: 937-44 [PubMed]
      2. Bhatt (2010) N Engl J Med 363:1909-17 [PubMed]

VII. Protocol: Perioperative Plavix

  1. Precautions
    1. See perioperative stenting implications above
    2. Mortality doubles in Acute Coronary Syndrome patients in first 90 days after stopping Plavix
      1. Consider tapering off by taking every other day for 2-3 weeks
      2. Conitinue Aspirin 162 after stopping Plavix
      3. Ho (2008) JAMA 299(5):532-9 [PubMed]
  2. Timing of stopping Plavix (if no contraindications)
    1. Stop 7 days before surgery (delay surgery if too soon after cardiovascular event)

VIII. Protocol: Perioperative Aspirin

  1. Precautions
    1. Aspirin used for secondary prevention
      1. Stopping Aspirin before surgery resulted in a 3 fold increased risk of cardiovascular events
    2. Aspirin used after coronary stenting
      1. Stopping Aspirin before surgery resulted in a 90 fold increasd risk of cardiovascular events
  2. Protocol
    1. Consult with surgeon regarding whether Aspirin may be continued
    2. Low dose Aspirin can be continued in the perioperative period for most surgeries
      1. Avoid Aspirin prior to intracranial surgery
      2. Avoid Aspirin prior to Prostatectomy
    3. Surgical bleeding risk increases with Aspirin by 20%
      1. However, no increase in severe bleeding for most surgeries (except intracranial surgery or Prostatectomy)
  3. References
    1. Eberli (2010) J Urol 183(6): 2128-36 [PubMed]
    2. Burger (2005) J Intern Med 257(5): 399-414 [PubMed]
    3. Biondi-Zoccai (2006) Eur Heart J 27(22): 2667-74 [PubMed]

IX. References

  1. Dehmer (2009) Am Fam Physician 80(11): 1245-53 [PubMed]
  2. Hannan (2008) Circulation 117(16): 2071-8 [PubMed]
  3. Moses (2003) N Engl J Med 349:1315-23 [PubMed]
  4. Serruys (2001) N Engl J Med 344:1117-24 [PubMed]
  5. Tran (2004) JAMA 292:1867-74 [PubMed]

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