 | | 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 |
|  | | Slide 16 |
|
 | | 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 |
|
 | | Slide 49 |
|  | | Slide 50 |
|
 | | 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 |
|  | | 84 |
|
 | | 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 |
|  | | Slide 94 |
|
 | | 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 |
|  | | 104 |
|
 | | 105 |
|  | | 106 |
|
 | | 107 |
|  | | 108 |
|
 | | 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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