Optimal Medical Management of ACS

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Optimal Medical Management of ACS

• Khawar Kazmi

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ACUTE CORONARY SYNDROME
PATHOGENESIS
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Supportive Specific

• Oxygen
• Pain relief
• Beta blockers
• Nitrates

• Anti Platelets
• Anti Coagulants

It is crucial to ensure prompt recognition and
rapid delivery of care
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DUAL ANTI PLATLET

• Clopidogrel
• Early use in all cases as benefit in all risk
  categories with or without revascularization
• Loading dose 300 vs. 600mg
• Reloading in NSTMI prior to PCI
• No benefit in stable angina

• CURE, CREDO Trials
• ARMYDA-2 Trial
• CHARISMA Trial

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• Clopidogrel Resistance
• Resistance vs. Treatment Failure
• NONRESPONSE
• Definite entity but wide variation (4 30)
• Variable response to ADP
• Genetic Variability
• Positive interaction with Omega 3

J Am Coll Cardiol. 2010
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Clopidogrel and PPIs

• Data on PPI plus Clopidogrel show inconsistent
  risk of adverse outcome
• Meta Analysis show no increased risk of CV
  events or mortality
• 
  Ailment Pharmacol Ther. 2010

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Clopidogrel Duration and cessation

• Similar rates of cardiac death, MI regardless of
  stopping clopidogrel after 12 months
• Trend towards higher rates of MI, Stroke, or all
  cause death with prolonged dual therapy
• Under powered study does not provide definite
  answer to issue of optimal duration
• 
  
  N Engl J Med. 2010

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• PRASUGREL
• More effective esp. in patients with Clopidogrel
  Non Response
• Better primary efficacy endpoint
• (9.9 vs. 12.1.. Triton- TIMI 38)
• Increased Bleeding including life threatening
• (2.4 vs. 1.8)
• But mainly in patients with H/O stroke or TIA,
• patients gt75 years and those with body weight
  lt60kg

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• Ticagrelor
• Ticagrelor more effective than Clopidogrel
  without increasing bleeding
• Lowers CV death, MI, Stroke vs. Clopidogrel in
  STEMI
• Antiplatelet effect of Ticagrelor kicks in more
  rapidly than high dose Clopidogrel
• Ticagrelor improves platelet inhibition
  regardless of initial Clopidogrel response
• Urgent bypass pts on prior Ticagrelor have better
  survival than those on Clopidogrel
• 
  PLATO Trial. Lancet 2010
• 
  The ONSET/OFFSET Study
• 
  Respond Study. Circulation 2010
• 
  

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• CILOSTAZOL
• Triple therapy lowers platelet response on
  VerifyNow assay but
• Results do not translate to lower ischemic events
  in DES patients
• 
  CILON- T trial

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Anticoagulants

• LMWH vs. UFH
• Enoxaparin vs. Foundaparinaux
• Bivalirudin vs. GPIIb/IIIa plus Heparin

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Benefit-to-Risk Ratio of Antithrombotics in
UA/NSTEMI in the Last Decade Increased Efficacy
at the Price of Increased Bleeding
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Major Bleeding is Associated with an Increased
Risk of Hospital Death in ACS Patients
GRACE Registry in 24,045 ACS patients
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Moscucci et al. Eur Heart J 2003241815-23
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Strong, Independent Association Between Bleeding
and Death, MI and Stroke
OASIS Registry, OASIS-2, CURE
N 34,126
Outcome Major Bleed No Major Bleed Hazard (Adjusted) P- Value
Death 60/470 (12.8) 833/33676 (2.5) 5.37 (3.97-7.26) lt0.0001
MI 46/436 (10.6) 1375/33710 (4.1) 4.44 (3.16-6.24) lt0.0001
Stroke 12/469 (2.6) 187/33677 (0.6) 6.46 (3.54-11.79) lt0.0001
Eikelboom JW et al. Circulation
2006114(8)774-82.
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The OASIS 5 Study
OASIS 5

N Engl J Med 20063541464-76

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In Patients with UA/NSTEMI
OASIS 5

1. Fondaparinux was as effective as enoxaparin in
   reducing the composite of death, MI or refractory
   ischemia at day 9
2. Fondaparinux significantly reduced the risk of
   death by 17 compared with enoxaparin at day 30
   and this benefit was maintained at 6 months
3. Fondaparinux was associated with a significant
   48 reduction in the risk of major bleeding
   versus enoxaparin
4. Consistent results were observed in every
   subgroup examined
5. Fondaparinux consistently reduced the rate of
   major bleeding irrespective of renal function and
   baseline risk
6. The lower rate of bleeding in fondaparinux-treated
   patients translated into a lower mortality rate

OASIS 5 Investigators. N Engl J Med
20063541464-76
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Bivalirudin

• Bivalirudin alone compared to heparin and
  GPIIb/IIIa inhibitors resulted in comparable
  rates of MI and stent thrombosis, with
  significantly reduced rates of major bleeding and
  mortality(all cause and cardiac)

• At 2 years
• 36 reduction in major bleeding and 25 reduction
  in reinfarction
• 41 reduction in cardiac mortality and 25
  reduction in all cause mortality
• But the benefits were variable among the sub
  groups
• 
  HORIZON AMI Trial

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2007 AHA/ACC UA/NSTEMI Guidelines Recommendation
for Anticoagulation

• Class I Recommendations
• For patients in whom an invasive strategy is
  selected, regimens with established efficacy
  include fondaparinux, enoxaparin, UFH or
  bivalirudin
• For patients in whom a conservative strategy is
  selected, regimens with established efficacy
  include fondaparinux, enoxaparin or UFH
• In patients in whom a conservative strategy is
  selected and who have an increased risk of
  bleeding, fondaparinux is preferable.

LOA B for fonda and bivalirudin A for enoxaparin
or UFH
JACC 200750 (7)e1-157
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I will stop here but we will continue our search
for optimal medical therapy

• thank you