BIMODAL TT FOR acs PATIENT NEED EVALUTIOM TO MANG AT LEAST ONE YEAR POST ACS TO UMPROVE OYUT COME

1. IMPROVED
OUTCOMES
START HERE
STEMI
1041485.011
SA-3985; DOP: March 2021; DOE: March 2023

2. UNMET NEED IN STEMI MANAGEMENT
ACS PATIENTS IN THE GULF ARE A DECADE YOUNGER THAN THOSE IN
DEVELOPED COUNTRIES1-3
Adapted from:
1. Widimsky P. www.escardio.org/communities/councils/ccp/e-journal/volume5/Pages/voi5n40.aspx (accessed October 2011).
2. Scott IA, et al. Int J Qual Health Care 2004; 16:275-84. Tan WA. Unstable Angina. http://emedicine.medscape.com/article/159383-overview#a0156v (accessed October 2011)
3a. Gulf RACE II, Ann Saudi Med 2012;32920:9-18.
3b. Zubaid M, et al. Acta Cardiol 2009;64:439-46.

3. UNMET NEED IN STEMI MANAGEMENT3
ACS PATIENTS IN THE GULF ALSO PRESENT LATE TO THE HOSPITAL1-4
Adapted from:
1. Al Habib et al. Ann Saudi Med 2012; 32(2): 9-18.
2. Gibson et al. Am Heart J 2008; 156: 1035-44.
3. Eagle et al. Eur Heart J 2008; 29(5): 609-17.
4. Mandelzweig et al. Eur Heart J 2006; 27: 2285-2293
*Mediterranean Basin
MEDIAN TIME FROM SYMPTOMS ONSET TO HOSPITAL ARRIVAL FOR STEMI PATIENTS

4. Adapted from:
1. Fox K, et al. Time course of events in acute coronary syndromes: implications for clinical practice from the GRACE registry. Nature Clinical Practice/Cardiovascular Medicine 2008; 5(9): 580-89.
DEATH FROM HOSPITAL ADMISSION TO 6 MONTHS1
UNMET NEED IN STEMI MANAGEMENT
STEMI PATIENTS FACE A HIGH RISK OF MORTALITY WITHIN THE FIRST 6
MONTHS AFTER AN EVENT

5. Adapted from:
1. Fox K, et al. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J 2010; 31: 2755-2764.
UNMET NEED IN STEMI MANAGEMENT
STEMI PATIENTS ARE AT A CONTINUED RISK OF MORTALITY UP TO 5 YEARS
AFTER DISCHARGE1
SURVIVAL RATES OF STEMI PATIENTS WITHIN 5 YEARS

6. PLATO: STUDY DESIGN
A LANDMARK CLINICAL TRIAL PROVING THE SUPERIORITY OF BRILINTA IN
REDUCING CV MORTALITY VS. CLOPIDOGREL ACROSS A BROAD RANGE OF
ACS PATIENTS1-3
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca.
2. Wallentin L, et al. N Engl J Med 2009; 36; 1045-1057 supplemental information.
3. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057.

7. PLATO: STUDY DESIGN
A LANDMARK CLINICAL TRIAL PROVING THE SUPERIORITY OF BRILINTA
IN REDUCING CV MORTALITY VS. CLOPIDOGREL ACROSS A BROAD
RANGE OF ACS PATIENTS1-3, 4-6
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca
2. Supplementary Appendix to: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-1057.
doi: 10.1056/NEJMoa0904327.
3. Wallentin L, Becker RC, Budaj A, et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057.
4. Cannon CP, Harrington RA, James S, et al; PLATelet inhibition and patient Outcomes Investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive
strategy coronary Syndrome(PLATO0: a randomised double-blind study. L ancet. 2010;375:283-293.
5 James S, Akerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes :
rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009;157:599-605.
6. James S, Roe MT, Cannon CP, et al; PLATO Study Group. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management:
substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ.2011;342:d3527. doi:10.1136/bmj.d3527.
DEMONSTRATED EFFICACY IN A STUDY OF MORE THAN 18,000 ACS PATIENTS

8. PLATO: STUDY DESIGN
A LANDMARK CLINICAL TRIAL PROVING THE SUPERIORITY OF BRILINTA
IN REDUCING CV MORTALITY VS. CLOPIDOGREL ACROSS A BROAD
RANGE OF ACS PATIENTS1,2
Adapted from:
1. Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
2. James S et al. Circulation. 2012;125:2914-2921.

9. PLATO: EFFICACY & SAFETY RESULTS
BRILINTA 90MG ABSOLUTE RISK REDUCTION STARTS AS EARLY AS DAY
30 AND CONTINUES TO INCREASE THROUGHOUT THE 12 MONTHS1
Adapted from:
1. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057.
PRIMARY EFFICACY ENDPOINT: RISK REDUCTION TO 12 MONTHS

10. PLATO: EFFICACY & SAFETY RESULTS
BRILINTA 90MG DEMONSTRATED A 21% RRR IN CV MORTALITY VS.
CLOPIDOGREL
Adapted from:
1. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057.
SECONDARY EFFICACY ENDPOINT: CV MORTALITY AT 12 MONTHS1
Adapted from wallentin L et al. N Engl J Med 2009; 361: 1045-1057. supplementary information.1
All patients were on a background of aspirin therapy
months after
randomisation
CV
MORTALITY
(KM%)
0
1
2
3
4
6
5
n=18,62
4
0 2 4 6 8 1
0
1
2
BRILINTA 90mg
(n=9,333)
clopidogrel
(n=9,291)
H
R
0.7
9
95%
CI
0.69-
0.91
P=0.00
1
NNT=91

11. Adapted from:
1. Steg PG, et al. Circulation 2010; 122: 2131-2141.
PLATO STEMI SUBGROUP1
PLATO: EFFICACY & SAFETY RESULTS
IN THE STEMI SUBGROUP OF PLATO, BRILINTA 90MG DEMONSTRATED A
17% RRR IN CV MORTALITY VS. CLOPIDOGREL
HR 0.83
(0.67-1.02)
P=0.07

12. PLATO: EFFICACY & SAFETY RESULTS
BRILINTA 90MG DEMONSTRATED NO INCREASE IN OVERALL MAJOR
BLEEDING OR FATAL BLEEDING VS. CLOPIDOGREL1
Adapted from:
1. Wallentin L, et al. N Engl J Med 2009; 1045-1057.

13. PLATO: EFFICACY & SAFETY RESULTS
AT 12 MONTHS, BRILINTA SHOWED NO SIGNIFICANT INCREASE IN TOTAL
MAJOR BLEEDING VS. CLOPIDOGREL1
Adapted from:
1. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057.

14. PLATO vs. TIMI BLEEDING DEFINITIONS1
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca

15. PLATO: EFFICACY & SAFETY RESULTS
NO SIGNIFICANT DIFFERENCE IN MAJOR BLEEDING SEEN WITH BRILINTA1
Adapted from:
1. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057.
PLATO: MAJOR BLEEDING

16. PLATO: EFFICACY & SAFETY RESULTS
DYSPNOEA
Adapted from:
1. BRILINTA: Summary of product Characteristics, 2016.
2. Wallentin L, et al. N Engl J Med. 2009:361: 1045-1057.
3. Storey RF, Bliden K, Patil SB, et al. Abstract 5768: The Effect of Ticagrelor on Cardiopulmonary Function in Patients With Stable Coronary Artery Disease.Circulation 2009: 120:S1145-a-.

17. PRACTICAL
EVALUATION OF OUTCOMES IN A LARGE POPULATION OF REAL-WORLD ACS
PATIENTS TREATED WITH BRILINTA 90MG OR CLOPIDOGREL19
Adapted from:
19. Sahlén A, et al. Eur Heart J 2016; pii: ehw284 [Epub ahead of print].
Due to BRILINTA 90mg 12 months license, only 12 months sensitivity analysis of the primary endpoints can be shared during this presentation
for efficacy analysis.
Data from PRACTICAL, an observational study of 45,073 patients prospectively enrolled into the SWEDEHEART registry, patients who were discharged on either BRILINTA 90mg
or clopidogrel were evaluated for the composite primary endpoints of death, MI or stroke.19

18. PRACTICAL
STUDY DESIGN
Adapted from:
19. Sahlén A, et al. Eur Heart J 2016; pii: ehw284 [Epub ahead of print].
Data from PRACTICAL, an observational study of 45,073 patients prospectively enrolled into the SWEDEHEART registry, patients who were
discharged on either BRILINTA 90mg or clopidogrel were evaluated for the composite primary endpoints of death, MI or stroke.

19. PRACTICAL
BRILINTA WAS RAPIDLY ADOPTED IN SWEDEN FOLLOWING ITS LAUNCH AND
INCLUSION IN ESC GUIDELINES19
Adapted from:
19. Sahlén A, et al. Eur Heart J 2016; pii: ehw284 [Epub ahead of print].
WITHIN 9 MONTHS OF LAUNCH BRILINTA HAS ACHIEVED ALMOST 50% SHARE IN DAPT MARKET19
Data from PRACTICAL, an observational study of 45,073 patients prospectively enrolled into the SWEDEHEART registry, patients who were
discharged on either BRILINTA 90mg or clopidogrel were evaluated for the composite primary endpoints of death, MI or stroke.

20. PRACTICAL
BENEFITS OF BRILINTA 90MG IN PRACTICAL VS. CLOPIDOGREL SHOWED
CONSISTENCY WITH PLATO SECONDARY ENDPOINT IN A REAL-WORLD
SETTING AT 12 MONTHS12,18
Adapted from:
12. Wallentin L, et al. N Engl J Med 2009; 361: 1045-1057
18. Sahlén A, et al. Eur Heart J 2016; pii: ehw284 [Epub ahead of print].
BRILINTA 90MG WAS ASSOCIATED WITH A 0.85% HAZARD RATIO IN THE COMPOSITE OF ALL-CAUSE
DEATH, MI AND STROKE VS. CLOPIDOGREL AT 12 MONTHS12
*Graph adapted with 12-month sensitivity analysis data performed by PRACTICAL study team.
Data from PRACTICAL, an observational study of 45,073 patients prospectively enrolled into the SWEDEHEART registry. BRILINTA 90mg was associated
with a lower risk of all-cause death, MI or stroke vs. clopidogrel (crude rates 11.7% vs. 22.3%, respectively, with a multivariate risk adjusted HR 0.85, 95%
CI 0.78-0.93). Final values are adjusted for hospital and calendar time, age, sex, discharge medication, in-hospital course, presentation characteristics and
pre-existing comorbidities. As an observational study of real-world evidence, the data from this study are subject to potential confounding bias usually
associated with observational research. Data are for treatment at discharge and planned treatment duration only.18

21. PRACTICAL
BRILINTA 90MG DEMONSTRATED NO SIGNIFICANT INCREASE IN OVERALL
MAJOR BLEEDING VS. CLOPIDOGREL, CONSISTENT WITH RESULTS SEEN
IN PLATO
Adapted from:
12. Wallentin L, et al. N Engl J Med 2009; 36: 1045-1057. Supplemental information.
PRACTICAL PRIMARY SAFTEY END POINT (MULTIVARIATE RISK ADJUSTED) AT 12 MONTHS:
BLEEDING REQUIRING HOSPITALIZATION

29. Switching between oral P2Y12 inhibitors as per SmPc2:
Switching from clopidogrel 75 mg to ticagrelor 90 mg twice daily results in an
absolute IPA increase of 26.4% and switching from ticagrelor to clopidogrel
results in an absolute IPA decrease of 24.5%. Patients can be switched from
clopidogrel to ticagrelor without any interruption of antiplatelet effect.
Adapted from:
1. Valgimigli M et al. Eur Heart J. 2018;39:213-254. DOI:10.1093/eurheartj/ehx419.
2. Brilinta. Summary of Product Characteristics.
aClass of recommendation.
bLevel of evidence.
cContraindications for ticagrelor:previous intracranial haemorrhage
of ongoin bleedds.

30. aClass of recommendation.
bLevel of evidence.
cContraindications for ticagrelor:previous intracranial haemorrhage
of ongoin bleedds.
Adapted from:
1. Valgimigli M et al. Eur Heart J. 2018;39:213-254. DOI:10.1093/eurheartj/ehx419.
2. Brilinta. Summary of Product Characteristics.
Switching between oral P2Y12 inhibitors as per SmPc2:
Switching from clopidogrel 75 mg to ticagrelor 90 mg twice daily results in
an absolute IPA increase of 26.4% and switching from ticagrelor to
clopidogrel results in an absolute IPA decrease of 24.5%. Patients can be
switched from clopidogrel to ticagrelor without any interruption of
antiplatelet effect (see section 4.2).

33. GUIDELINES
FOR YOUR STEMI PATIENTS, MAJOR INTERNATIONAL GUIDELINES NOW PREFER
TICAGRELOR 90MG OVER CLOPIDOGREL FOR THE FIRST 12 MONTHS1-3
Adapted from:
1. Neumann FJ et al. Eur Heart J. 2019; 40(2):87-165 DOI:10.1093/eurheartj/ehy394.
2. Ibanez B et al. Eur Heart J 2018: 1-66. DOI: 10.1093/eurheartj/ehx393.
3. Levine GN et al. Circulation 2016:DOI; 10.1161/CIR.00000000000000404.
LOE, Level of evidence; PCI=percutaneous coronary intervention; STEMI=ST-elevation myocardial infarction; DAPT=dual antiplatelet therapy
*Drug eluting stent or bare metal stent implantation

34. CONCLUSION
BRILINTA IS SIMPLE AND EFFECTIVE IN THE MANAGEMENT OF YOUR ACS
PATIENTS FOR UP TO 12 MONTHS*1,2
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca
2. Wallentin L, et al. N Engl J Med 2009; 361: 1045-1057.
✝Unless contraindicated

35. CONCLUSION
BRILINTA IS SIMPLE TO USE WITHIN A BROAD RANGE OF ACS PATIENTS
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca.
BRILINTA LOADING IS NOT RESTRICTED BY1:

36. Adapted from:
1. Brilinta SmPC 2016. AstraZeneca
2. Wallentin L, et al. N Engl J Med 2009; 361: 1045-1057. Supplementary information.
3. Wallentin L, et al. N Engl J Med 2009; 361: 1045-1057.
4. Windecker S, et al. Eur Heart J 2014: 2541-2619.
5. Levine GN, et al. Circulation 2016; DOI; 10.1161
6. Jemberg T, et al. Eur Heart J 2015; 136: 1163-1170.
CONCLUSION
BRILINTA, IN COMBINATION WITH LOW DOSE ASA, PROTECTS YOUR MI
PATIENTS AGAINST SUBSEQUENT EVENTS FOR UP TO 12 MONTHS1
*In combination with low dose aspirin

38. BRILINTA IS THE FIRST IN A NEW CHEMICAL CLASS OF
OAPs DIFFERENT FROM THIENOPYRIDINES1,2
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca.
2. Husted S, et al. Cardio Ther 2009;27:259-274.

39. THE DUAL PATHWAY MEDIATES BOTH ANTI-PLATELETS
EFFECTS AND ENHANCED ADENOSINE RESPONSE
Adapted from:
1. Van Giezen JJJ, et al. J Thromb Haemost 2009;7:1556-1565.
2. Wallentin L. Eur Heart J 2009;30:1964-1977.
3. Nylander S. et al. J Thromb Haemost 2013;11:1867-1876.
4. Armstrong D. et al. J Cardiovasc. Pharmacol Ther; In press.
5. Van Giezen JJJ, et al. J Cardiovasc. Pharmacol Ther 2012;17;164-172.
6. Wang K. et al. Thromb Haemost 2010;104:609-17.
7. Wittfeldt A. et al. J Am CollCardiol 2013;61:723-727.

40. BRILINTA IS DIRECT ACTING; UNLIKE THIENOPYRIDINES ARE
PRO-DRUGS1
Figure Adapted from
1. Schoming A (2009) CYP, cytochrome P450. Schoming A. N Engl J Medicine 2009;361:1108-1111.

41. BRILINTA DELIVERS MORE RAPID PLATELET
INHIBITION VS. CLOPIDOGREL1,2
Adapted from:
1. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery
disease: the ONSET/OFFSET study. Circulation 2009;120:2577-2585.
2. Brilinta SmPC 2016, AstraZeneca.

42. ONSET/OFFSET: INHIBITION OF PLATELETS
AGGREGATION1
Adapted from:
1. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease:
the ONSET/OFFSET study. Circulation 2009;120:2577-2585.

43. BRILINTA IS INDICATED FOR USE EITHER WHOLE,
OR AS CRUSHED TABLETS1,2
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca.
2. Teng R. Clin Pharmacokinet. 2015;54:1125-1138.
Administration of crushed 90mg tablets (orally or via nasogastric tube) resulted in higher ticagrelor plasma concentrations
at early timepoints (0.5 and 1 h) vs. whole tablets*2
*36 healthy subjects were randomized in this open-label, three-period, three-treatment crossover study

44. ACS PATIENTS RECEIVING BRILINTA HAD FEWER
DEFINITE STENT THROMBOSIS VS. PATIENTS
RECEIVING CLOPIDOGREL 1,2
Adapted from:
1. Brilinta SmPC 2016. AstraZeneca.
2. Wallentin L, Becker RC. Budaj A, et al. PLATO Investigators. Ticagrelor versus Clopidogrel in Patients with Acute Cornary Syndrome. N Engl J Med. 2009; 361 (11):1045-1057.
INCIDENCE OF STENT THROMBOSIS AT 12 MONTHS
With BRILINTA® vs clopidogrel, risk of definite stent thrombosis
was reduced by one third

45. Patients with concomitant administration of medicinal products that
may increase the risk of bleeding (e.g. non-steroidal anti-
inflammatory drugs (NSAIDs), oral anticoagulants and/or
fibrinolytics) within 24 hours of ticagrelor dosing.
SPECIAL WARNINGS AND PRECAUTIONS FOR USE