1) The PLATO study found that ticagrelor was superior to clopidogrel for reducing cardiovascular events in patients with acute coronary syndrome, with a relative risk reduction of 16% and number needed to treat of 54. 2) The ATLAS study found that rivaroxaban was effective for secondary prevention of cardiovascular events with lower rates of bleeding compared to aspirin alone. 3) Several studies explored new antiplatelet and anticoagulant drugs for treatment and secondary prevention of acute coronary syndrome.

1. CARDIOACTUALIDAD: LO MÁS RELEVANTE DE LA CARDIOLOGÍA EUROPEA Y MUNDIAL EN EL ÚLTIMO AÑO CARDIOPATÍA ISQUEMICA Dra. Magda Heras ICT, Hospital Clínic, Barcelona Congreso Nacional Enfermedades CV Barcelona, Octubre 2009

4. PLATO Study Design Primary endpoint: • CV death + MI + Stroke Key secondary: • CV death + MI + Stroke in patients intended for invasive management • Total mortality + MI + Stroke • CV death + MI + Stroke + recurrent ischaemia + TIA + arterial thrombotic events • MI alone / CV death alone / Stroke alone / Total mortality Primary safety: • Total major bleeding 6–12 month exposure Clopidogrel If pre-treated, no additional loading dose; if naive, standard 300 mg loading dose, then 75 mg qd maintenance; (additional 300 mg allowed pre PCI) Ticagrelor 180 mg loading dose, then 90 mg bid maintenance; (additional 90 mg pre-PCI) UA/NSTEMI (moderate-to-high risk) STEMI (if primary PCI) All receiving ASA; clopidogrel-treated or naive; randomised within 24 hours of index event (N=18,624) James S, et al. Am Heart J . 2009;157:599-605.

5. TICAGRELOR IN ACS. THE PLATO STUDY Hierarchical Testing of Major Efficacy Endpoints Wallentin L, et al. New Engl J Med. 2009;361. All Patients* Ticagrelor (n=9,333) Clopidogrel (n=9,291) HR for ticagrelor (95% CI) P value ✝ Primary Objective, n (%/yr) CV death + MI + stroke 864 (9.8) 1,014 (11.7) 0.84 (0.77-0.92) 0.0003 Secondary Objectives, n (%/yr) Total death + MI + stroke 901 (10.2) 1,065 (12.3) 0.84 (0.77-0.92) 0.0001 CV death + MI + stroke + severe + recurrent ischemia + TIA + arterial thrombus 1,290 (14.6) 1,456 (16.7) 0.88 (0.81-0.95) 0.0006 MI 504 (5.8) 593 (6.9) 0.84 (0.75-0.95) 0.0045 CV death 353 (4.0) 442 (5.1) 0.79 (0.69-0.91) 0.0013 Stroke 125 (1.5) 106 (1.3) 1.17 (0.91-1.52) 0.2249 Total Death 399 (4.5) 506 (5.9) 0.78 (0.69-0.89) 0.0003

6. No. at risk Clopidogrel Ticagrelor 9,291 9,333 8,521 8,628 8,362 8,460 8,124 Days after randomisation 6,743 6,743 5,096 5,161 4,047 4,147 0 60 120 180 240 300 360 12 11 10 9 8 7 6 5 4 3 2 1 0 13 Cumulative incidence (%) 9.8 11.7 8,219 Clopidogrel Ticagrelor K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval Wallentin L, et al. New Engl J Med. 2009;361. TICAGRELOR IN ACS. THE PLATO STUDY Death, MI or Stroke p=0.0003 HR 0.84 (95% CI 0.77–0.92 ) RRR = 16%, ARR = 1.87%, NNT = 54

7. Mehta S, et al ESC 2009, Hot Line

8. CLOPIDOGREL IN ACS. THE CURRENT STUDY Mehta S, et al ESC 2009, Hot Line

9. PRASUGREL IN STEMI. THE TRITON – TIMI 38 STUDY Montalescot G et al. Lancet 2009; 373: 723–31

10. PRASUGREL IN STEMI. THE TRITON – TIMI 38 STUDY Montalescot G et al. Lancet 2009; 373: 723–31 Death, MI, stroke Death, MI, urgent TVR Stent thrombosis TIMI major bleeding, non-CABG related

12. OTAMIXABAN IN NSTEMI. THE SEPIA-ACS 1 STUDY Sabatine M. ESC 2009 [ figura REC 2009;62:1149-60]

13. GP IIb/IIIa antagonists in STEMI . The BRAVE-3 study 800 pts with AMI ≤ 24h ASA, heparin, 600 mg clopidogrel. Abciximab vs placebo before pPCI 1º end-point: Infarct size (SPECT) 2º: Death+AMI+TVR+stroke 30 d. No differences in major bleeding Mehilli J, et al. Circulation 2009;119: 1933-40 % pts

14. ROUTINE PCI AFTER FIBRINOLYSIS IN STEMI The TRANSFER study 1059 pts with high risk AMI ≤ 12h, in non-PCI centres ASA, TNK, heparin, clopidogrel (recom). Randomized early routine PCI ≤ 6h (99%) vs standard treatment (1/3 required urgent PCI) 1º end-point: Death+AMI+ Rec isch+ CHF, shock 30 d. Cantor WJ, et al. NEJM 2009;360: 2705-18 P=0.004 P=0.003 P=0.04 RR 0.64 0.09 0.54 % pts

15. PRIMARY PCI VS FIBRINOLYSIS IN STEMI IN THE ELDERLY. The TRIANA study 266 pts with AMI > 75 yrs, admitted to active p PCI (23 centres) Randomized to pPCI vs TNK ASA, heparin, clopidogrel (recom). 1º end-point: Death+AMI+ stroke 30 d. Bueno H, et al ESC 2009, Hot Line OR 1.31 (0.67-2.56) P = 0.43 OR 1.60 (0.60-4.25) P = 0.35 OR 4.03 (0.44-36.5) P = 0.18 OR 1.46 (0.81-2.61) P = 0.21

17. Mega JL, et al. Lancet 2009; 374: 29-38 RIVAROXABAN IN SECONDARY PREVENTION. THE ATLAS STUDY N= 3.491 N= 2.730 N= 761

18. RIVAROXABAN IN SECONDARY PREVENTION. THE ATLAS STUDY Mega JL, et al. Lancet 2009; 374: 29-38 BLEEDING 2 EFFICACY 5,5 3,9 1 EFFICACY 5,6 7,0

19. APIXABAN IN SECONDARY PREVENTION. THE APPRAISE STUDY Appraise Investigators. Circulation 2009; 119: 2877- 85 CR: Clinically relevant Apixaban 2,5 HR 1,78, NS Apixaban 10 HR 2,45, p=0,005 BLEEDING ISTH MAJOR, CR NON-MAJOR Apixaban 2,5 HR 0,73, NS Apixaban 10 HR 0,61, p=0,07 EFFICACY DEATH, MI, REC ISCH, STROKE

20. THROMBIN RECEPTOR ANTAGONIST SCH 530348 THE TRA-PCI STUDY Becker RC, et al Lancet 2009; 373: 919-28