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Improving outcomes with antithrombotics in patients at risk of vascular events

Slides (presentatie) - Mar. 25, 2010

Improving Outcomes with Antithrombotics in Patients at Risk of Vascular Events

Improving outcomes with antithrombotics in patients at risk of vascular events Dutch Atherosclerosis Society 25 March 2010

„Fathers“ of invasive cardiology

Lenfant C. N Engl J Med 2003;349:868-974

Plaque growth and rupture

Plaque ruptuur met totale afsluiting

The great attack on plaque growth and rupture

Balance of Hemostasis and Thrombosis

Adapted from Brouwer MA, Verheugt FWA. Circulation 2002;105:1270-1274

Aspirin and P2Y12 ADP Antagonists: Mechanisms of Action

Slide 11

ACUTE CORONARY SYNDROMES

Slide 13

ASSENT-2. Lancet 1999;354:716-722

Primary PCI versus Thrombolysis

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ASPIRIN AND HEPARIN PRIOR TO PRIMARY PCI

Clopidogrel Trials – ACS/CAD

Ross AM. J Am Coll Cardiol 1999;34:1954-1962

Van den Merkhof LFM. JACC 1999;33:1528-1532

Adjunctive abciximab has been shown to reduce mortality in STEMI patients undergoing PPCI Mortality 6 Months

ESC PCI Guidelines

The most critical point for PPCI is TIME GOLDEN PERIOD for myocardial salvage is first 2 hrs

In-ambulance abciximab administration in STEMI patients undergoing primary PCI is associated with smaller infarct size, improved LV function and lower incidence of heart failure: Results from the Leiden MISSION! infarct treatment optimization program Catheterization and Cardiovascular Interventions, Epub 2009 Jan

The MISSION! protocol is a rigorously standardized protocol. Contains a pre-hospital, in-hospital, and outpatient clinical framework for decision making and treatment, up to 1 year after the index event.

Aim of our Mission! Early vs late abciximab study

Study groups

End points of the study

Results

Baseline characteristics of the study population

TREATMENT TIME INTERVALS

Angiographic and procedural results

Primary angiographic endpoint: IRA patency

Aborted Myocardial Infarction in patients with STEMI treated with PPCI and early (in ambulance) vs late (in cathlab) abciximab.

Secondary endpoints: 1) ST- segment resolution ≥ 70% at 90 min post PPCI

Secondary endpoints: 2) Enzymatic infarct size (by cumulative 48h CK release)

Secondary endpoints: 3) Three-month LV function results by gated SPECT

Clinical outcome at follow-up (median 7 months)

Limitations

Key findings of the early vs late abciximab MISSION substudy (STEMI patients treated with PPCI)

(n=3,366)

(n=3,366)

BRAVE-3 presented ACC 08

BRAVE-3 presented ACC 08

BRAVE-3 presented ACC 08

ACUTE CORONARY SYNDROMES

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

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Clopidogrel Trials – ACS/CAD

Oral Antithrombotics

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

Aspirin and P2Y12 ADP Antagonists: Mechanisms of Action

Background

Prasugrel: Active Metabolite Formation Faster Onset of IPA

Is faster always better to reach your goal?

Healthy Volunteer Crossover Study

   

Balance of Efficacy and Safety

Ticagrelor (AZD 6140): an oral reversible P2Y12 antagonist

Note: Prasugrel must be metabolized to its active form. For Ticagrelor, both the parent compound and metabolites are active.

Study Objectives

NSTE-ACS (Trop 80%) STEMI (if primary PCI 37%) Clopidogrel-treated or -naive; randomised within 24 hours of index event (N=18,624)

Wallentin L et al. N Engl J Med. 2009;361:1045-57

Wallentin L et al. N Engl J Med. 2009;361:1045-57

PLATO

Bleeding Definitions

PLATO vs. TRITON: Key Differences

PLATO vs. TRITON: Key Differences

Slide 72

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

Balance of Hemostasis and Thrombosis

Aspirin and P2Y12 ADP Antagonists: Mechanisms of Action

Development Strategy for Thrombin Receptor Antagonist

TRA Background

Research = Investigation!

Patients with high-risk Non-ST-Segment Elevation Acute Coronary Syndrome

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

Adapted from Brouwer MA, Verheugt FWA. Circulation 2002;105:1270-1274

Desirable qualities of a new anticoagulant

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Slide 85

PROPERTIES OF PATENTERAL ANTICOAGULANTS

Simoons ML. J Am Coll Cardiol 2004;43:2183-2190

Simoons ML. J Am Coll Cardiol 2004;43:2183-2190

N Engl J Med 2006;354:1464-76

N Engl J Med 2006;354:1464-76

N Engl J Med 2006;354:1464-76

NOVEL LONG-TERM Anti-Coagulants Anti-Platelet Agents

ESTEEM

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RE-LY

Connoly SJ et al. N Engl J Med. 2009;361:1139-1151.

Conclusion RELY: in NVAF dabigatran is better, safer and more user-friendly than warfarin

Combined analysis of dabigatran trials

Conclusions

NOVEL LONG-TERM I. Anti-Platelet Agents II. Anti-Coagulants

Slide 101

APPRAISE

APPRAISE

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105

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ATLAS ACS-TIMI 46

Antithrombotic Therapy in ACS 2009

NOVEL LONG-TERM I. Anti-Platelet Agents (Prasugrel/Ticagrelor/Thrombin-Rec.-Inhib.) II. Anti-Coagulants (Factor Xa inhibitors, Thrombin (fact II) inhibitors)

New Antithrombotics -

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