΢ΠΤΡΟ΢ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD....

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Transcript of ΢ΠΤΡΟ΢ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD....

  • NOVEL ANTIPLATELET

    DRUGS

    IN ACS

    ΢ΠΤΡΟ΢ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD. PHD. FESC

    ΕΙΔΙΚΟ΢ ΚΑΡΔΙΟΛΟΓΟ΢

    ΔΙΔΑΚΣΩΡ ΑΠΘ

    ΑΝΑΠΛΗΡΩΣΗ΢ ΔΙΕΤΘΤΝΣΗ΢ ΚΑΡΔΙΟΛΟΓΙΚΗ΢

    ΚΛΙΝΙΚΗ΢ ΝΑΤΣΙΚΟΤ ΝΟ΢ΟΚΟΜΕΙΟΤ ΑΘΗΝΩΝ

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • August 30, 2009 at 08.00 CET

  • PLATO background

     In NSTE-ACS and STEMI, current guidelines

    recommend 12 months aspirin and clopidogrel

     Efficacy of clopidogrel is hampered by

     slow and variable transformation to the active metabolite

     modest and variable platelet inhibition

     increased risk of bleeding

     risk of stent thrombosis and MI in poor responders

  • K-M estimate of time to first primary efficacy

    event (composite of CV death, MI or stroke)

  • Secondary efficacy endpoints

  • Stent thrombosis

    Ticagrelor

    (n=5,640)

    Clopidogrel

    (n=5,649)

    HR

    (95% CI) p value

    Stent thrombosis, n (%)

    Definite

    Probable or definite

    Possible, probable, definite

    71 (1.3)

    118 (2.1)

    155 (2.8)

    106 (1.9)

    158 (2.8)

    202 (3.6)

    0.67 (0.50–0.91)

    0.75 (0.59–0.95)

    0.77 (0.62–0.95)

    0.009

    0.02

    0.01

  • Time to major bleeding – primary

    safety event

  • Total major bleeding

  • Conclusions  Reversible, more intense P2Y12 receptor inhibition for one year

    with ticagrelor in comparison with clopidogrel in a broad

    population with ST- and non-ST-elevation ACS provides

     Reduction in myocardial infarction and stent thrombosis

     Reduction in cardiovascular and total mortality

     No change in the overall risk of major bleeding

    Ticagrelor is a more effective alternative than clopidogrel

    for the continuous prevention of ischaemic events, stent

    thrombosis and death in the acute and long-term treatment

    of patients with ACS

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • TRITON TIMI-38

  • Study Overview

     Antiplatelet therapy with aspirin and a thienopyridine is a key component in the management of acute coronary syndromes

     This trial compared a novel, potent thienopyridine (prasugrel) with the standard thienopyridine (clopidogrel) in patients with acute coronary syndromes scheduled to have a coronary intervention

     Prasugrel led to better cardiovascular outcomes, but at the expense of more bleeding, including fatal bleeding

  • A shows data for the primary efficacy end point (death from cardiovascular

    causes, nonfatal myocardial infarction [MI], or nonfatal stroke) and for the key

    safety end point (Thrombolysis in Myocardial Infarction [TIMI] major bleeding not

    related to coronary-artery bypass grafting) (bottom) during the full follow-up

    period. The hazard ratio for prasugrel, as compared with clopidogrel, for the primary

    efficacy end point at 30 days was 0.77 (95% confidence interval [CI], 0.67 to 0.88;

    P

  • TRITON TIMI 38

  • TRITON Diabetic Subgroup

  • TRITON STEMI cohort

    Primary EP (CV death, MI and stroke at 15 months)

  • TRITON Net Clinical Benefit

    Bleeding Risk Subgroups

  • Conclusion

     In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding

     Overall mortality did not differ significantly between treatment groups

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • CANGRELOR

     A NOVEL INTRAVENOUS ANTIPLATELET AGENT??

    •ATP analogue

    •Relatively resistant to the

    breakdown of endonucleotidases

    •Not require metabolic activation

    • Reversible competitive

    antagonist

    •Administered intravenously

    •Th

  • CANGRELOR

     CHAMPION PCI – CHAMPION PLATFORM

    Negative Trials But Some Positive Angles for Cangrelor?

    Both trials were discontinued prematurely due to insufficient evidence of the

    clinical effectiveness of cangrelor.

    There were, however, reductions in stent thrombosis and death from any

    cause.

  • CHAMPION PHOENIX

    Cangrelor

  • CHAMPION PHOENIX Cangrelor Cuts Complications at PCI vs Clopidogrel in

    CHAMPION-PHOENIX; Bleeding a Caution

  • CANGRELOR

    February 12, 2014

     Administration (FDA) advisory panel voted 7 to 2 that cangrelor (the Medicines Company, Parsippany, NJ), an intravenously administered antiplatelet agent, should not be approved for the reduction of thrombotic cardiovascular events in patients with coronary artery disease undergoing PCI.

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • ELINOGREL  The only reversible and competitive P2Y12 receptor antagonist

     Direct-acting: no metabolic activation required

     Available for intravenous and oral administration, enabling acute and chronic use

     Immediate and near maximal platelet inhibition achieved with IV

     Duration of action

     Half-life: 12 hours

     No major CYP metabolism – low potential for drug-drug interactions (including PPIs)

     Balanced clearance: 50% renal; 50% hepatic (10% metabolized to pharmacologically inactive metabolite)

  • INNOVATE PCI-treatment schema

  • Clinical Endpoints

  • Bleeding at 24 hours

    *mainly on access site

  • Adverse Events

    * Dyspnea was generally mild, transient, and infrequently led to discontinuation

    ^ Most cases occurred within first 60 days and were asymptomatic; All cases resolved, even

    when treatment was continued; No Hy’s Law cases.

  • Conclusions

     IV and oral elinogrel result in greater and more rapid antiplatelet effect than clopidogrel during both the acute and chronic phase of therapy

     No excess TIMI major or minor bleeding at both the 24- hr and 120-day timepoints

     Dose-dependent trend of increase in less severe bleeds (Bleeding Requiring Medical Attention), mostly occurring at the vascular access site in the peri-procedural period

     No significant differences in efficacy at 24 hrs or 120 days (trial not powered for efficacy)

  • ΠΕΡΙΕΧΟΜΕΝΑ

    1. Novel antiplatelet agents-Mechanism of action

    2. Ticagrelor

    3. Prasugrel

    4. Cangrelor

    5. Elinogrel

    6. Guidelines (ESC-AHA)

  • Conclusions

    NEW ANTIPLATELET AGENTS ARE:

    Effective

    Rapid

    Safe

    And,,, In the future they could lead to decrease of the duration of DAPT in

    patients with with ACS and PCI with stent implantation if combined

    with new generation stents