A Michael Lincoff MD

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Anticoagulation to the max

• A Michael Lincoff MD
• Cardiologist
• Division of Cardiology
• Cleveland Clinic
• Cleveland, OH

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Anticoagulation to the max
Bivalirudin (Angiomax)

• A synthetic molecule
• Structure based on study of the saliva of the
  medicinal leech
• Directly and reversibly binds to thrombin
  molecule at 2 sites

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Anticoagulation to the max
Bivalirudin vs heparin

• Heparin has difficulty penetrating clot,
  indirect binding, indirect thrombin inhibitor,
  neutralized by circulating inhibitors, depends on
  a circulating antithrombin
• Bivalirudin easy penetration, direct binding,
• direct thrombin inhibitor, not neutralized by
  circulating inhibitors, acts independently of a
  circulating antithrombin

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Anticoagulation to the max
3 of 4
Hirulog angioplasty trial
1993-4 (balloon angioplasty era). 4000-patients. E
fficacy bivalirudin is as effective as heparin
in reducing ischemic complications, in
high-risk patients, is more effective. Safetya
marked reduction in rate of bleeding in patients
who received bivalirudin instead of heparin.
N Engl J Med 1995333(12)764-9
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Anticoagulation to the max
2 of 4
CACHET trial

• CACHET a pilot study of how bivalirudin
  interacts with IIb/IIIa inhibitors
• (Hirulog angioplasty trial was carried out before
  the stenting IIb/IIIa era)
•  Compared bivalirudin in various doses with
  abciximab, and without abciximab (bail-out
  approach) vs heparin abciximab
•  Resultstreatments with bivalirudin are at
  least equivalent in efficacy and safety as
  treatments with heparin.

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Anticoagulation to the max
Low-molecular-weight heparin

• We lack data from large-scale, randomized trials
  showing low-molecular weight heparin is better
  than unfractionated heparin in coronary
  intervention.
•  
• Limited data in the current era of coronary
  interventions support the superiority of
  bivalirudin to heparin.
•  
• We need the large-scale REPLACE trial.

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Anticoagulation to the max
Bivalirudin vs lepirudin

• Lepirudin (Refludan), a hirudin, is approved for
  treatment of heparin-induced thrombocytopenia.
• Hirudin irreversible inhibition of thrombin,
  dependence on renal function, significantly
  increased bleeding
• Bivalirudin reversible inhibition of thrombin,
  independent of renal function, no increased
  bleeding

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Anticoagulation to the max
Cost effectiveness?

• There is planned economic component to the
  REPLACE trial.
• Savings with bivalirudin relative to heparin
  expected
• 1) by allowing physicians to direct use of
  IIb/IIIa to patients at high risk
• 2) by reducing bleeding complications. (Expense
  of a major bleeding event equals that of
  angioplasty or bypass surgery)
•  

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Anticoagulation to the max
Summary

• Bivalirudin appears to be a safe and suitable
  replacement for heparin.
•  
• How bivalirudin works with IIb/IIIa inhibitors,
  and with setting, remains to be determined.