ΠΑΝΕΠΙΣΤΗΜΙΟ ΙΩΑΝΝΙΝΩΝ

Transcription

1 ΠΑΝΕΠΙΣΤΗΜΙΟ ΙΩΑΝΝΙΝΩΝ ΕΡΕΥΝΗΤΙΚΟ ΚΕΝΤΡΟ ΑΘΗΡΟΘΡΟΜΒΩΣΗΣ Σημαντικές Εξελίξεις στη Θρόμβωση TRA 2P TIMI 50 και TRACER Substudies ΚΑΛΑΝΤΖΗ ΚΑΛΛΙΡΡΟΗ Καρδιολόγος ιδάκτωρ Ιατρικής Σχολής Πανεπιστημίου Ιωαννίνων

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3 Trial Design Placebo NSTE Acute Coronary Syndromes 1:1 Randomized Double-blind Key inclusion criteria Within 24 hrs of symptoms biomarkers or ECG changes 1 other high-risk feature Vorapaxar Loading: 40 mg Maintenance: 2.5 mg daily Follow-up: 1, 4, 8, 12 months, then every 6 months Standard of care based on practice guidelines Efficacy Endpoints Primary: CV death, MI, stroke, hospitalization for ischemia, urgent revascularization Key Secondary: CV death, MI, stroke Bleeding Endpoints: GUSTO moderate or severe and clinically significant TIMI bleeding

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9 1580 MI events in 1319 patients Vorapaxar significantly reduced the hazard of a first MI of any type by 12% and the hazard of total number of MIs by 14%. Eur Heart J 2013;34:

10 64.9% type1 MI 22.3% type 4a MI (PCI related) Type 1 MI occurred in significantly less patients in the vorapaxar group (not for type 4a MI) Eur Heart J 2013;34:

11 2/3 of participants had a history of MI. 52% STEMI, 41% non STEMI, 7% unknown Lancet 2012;380: Table adopted by Moschonas et al, International Journal of Cardiology, 2015;185:9 18

12 In patients with previous MI and DM, the addition of vorapaxar to standard therapy significantly reduced the risk of major vascular events with greater potential for absolute benefit in this group at high risk of reccurrent ischemic events Circulation 2015;131:

13 58% PCI with BMS or DES The effect of vorapaxar, among patients with PCI, is consistent with the overall TRACER results. Patients with BMS displayed trends towards greater ischemic benefit from Vorapaxar vs Am J Cardiol 2014;114: patients with DES.

14 Patients with BMS displayed trends towards lesser bleeding from Vorapaxar vs patients with DES. Am J Cardiol 2014;114:665 73

15 53% history of PCI 1.4% ST in 3year follow up (92% late or very late ST) Vorapaxar significantly reduced definite ST, including very late thrombosis J Am Coll Cardiol 2014;64:

16 Vorapaxar increased GUSTO moderate/severe bleeding J Am Coll Cardiol 2014;64:

17 The reduction on ST was consistent in all subgroups prior STEMI,DES or BMS, smoking. DM patients had a numerically greater reduction in definite ST 83% on DAPT (98% clopidogrel) J Am Coll Cardiol 2014;64:

18 7.2% history of PAD The relative effect of Vorapaxar compared with placebo on the primary efficacy composite outcome was similar in patients with or without PAD (numerically lower for vorapaxar) Am Heart J 2014;168:588 96

19 There were trends favoring Vorapaxar in patients with or without PAD for the individual efficacy endpoints without reaching statistical significance. Stroke PAD Vorapaxar increased bleeding in both patients with and without PAD Am Heart J 2014;168:588 96

20 14.3% history of PAD Vorapaxar did not reduce the risk of CVD, MI or Stroke in patients with PAD Circulation 2013;127:

21 Vorapaxar significantly reduced acute limb ischemia peripheral revascularization Circulation 2013;127:

22 When including events involving coronary and cerebral circulations Vorapaxar significantly reduced urgent vascular hospitalization. Circulation 2013;127:

23 The beneficial effect of vorapaxar on limb vascular events were accompanied by an increased risk of bleeding Circulation 2013;127:

24 10.1% underwent CABG during index hospitalization, 78% on the study drug at the time of surgery. Vorapaxar was associated with a significant reduction in ischemic events compared with placebo. J Am Coll Cardiol 2014;63:

25 No significant increase in CABG related bleeding numerically higher with vorapaxar with no excess on fatal bleeding or need for reoperation J Am Coll Cardiol 2014;63:

26 Vorapaxar reduces ischemic stroke in patients with MI or PAD and no prior Stroke or TIA. J Am Coll Cardiol 2014;64:

27 There does not appear to be a significant increase in the incidence in the risk of hemorrhagic conversion or death in patients who experienced a first ischemic stroke on Vorapaxar. J Am Coll Cardiol 2014;64:

28 J Am Coll Cardiol 2014;64:

29 Although hemorrhagic stroke was increased, Vorapaxar led to a significant reduction in overall stroke J Am Coll Cardiol 2014;64:

30 Most TRACER participants were treated with low dose ASA, although a high dose was common in North America. High dose participants tended to have higher rates of ischemic and bleeding outcomes. NS. Consistent trends support use of low dose ASA with other antiplatelet therapies Am J Cardiol 2014;113:936 44

31 No interaction between vorapaxar and clopidogrel after non STEMI ACS on efficacy and safety outcomes Complementary role of PAR 1 and P2Y12 antagonism Am Heart J 2014;168:869 77

32 Lancet 2012;380:

33 There was no interaction between GP IIb/IIIa and vorapaxar s safety and efficacy. Nonetheless the combination increased the bleeding risk. Am J Cardiol 2015 Feb 18

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