1. The Management of ACS “Updated Perspectives and Goals” Rafid F. Al-Aqeedi FIBMS ( Med ), MRCP (London), DM ( Int.Card.), FACC, FESC Consultant Interventional Cardiologist Hawler Teaching Hospital, Hawler Cardiac Center Hawler Teaching Hospital, Hawler Cardiac Center Erbil ACS Forum 30 th November 2018, Divan Hotel, Erbil Kurdistan Copyright © 2018

2. Question ? In The Management of ACS How often you feel that non-invasive therapy is your current & effective primary goal of treatment? A.The majority i.e. >75% B.About 50% of patients C.Only minority (25%) D.Rarely

3. Coronary Heart Disease 187.4 death/100,000

4. Physicians have several goals when treating a patient with ACS:  To relieve ischemia and associated discomfort  To restore blood flow and prevent complete vessel occlusion in patients with NSTE-ACS, and preventing infarction expansion in both patients with STEMI or NSTE-ACS  To prevent complications or death ACS Acute Treatment Goals

5. To achieve these goals, the single most important step to do is:  Vital signs monitoring  Cardiac biomarkers test  GRACE / TIMI risk assessment  Asses previous cardiac history

6. NSTE-ACS Reperfusion Treatment Strategies

7. Risk Assessment 7 Risk assessment is used to help physicians determine whether to pursue an initially conservative strategy or an invasive strategy:

8. TIMI Risk Score 8 The TIMI risk score is a clinical characteristics used at presentation to estimate the early risk for patients hospitalized with ACS and can be factored into a physician’s decision regarding whether to pursue an: Initial conservative strategy or Invasive strategy for patients with NSTE-ACS

9. GRACE Risk Score Components 9 The higher the total points, the greater the risk. Like TIMI risk scoring, GRACE risk scores can be useful to clinicians in guiding treatment type and intensity.

10. GRACE & TIMI Risk Score

11. NSTE-ACS Selection of Acute Treatment Strategy Is a critical strategic decision required whether to move with an invasive or an initially conservative treatment strategy. The invasive strategy involves diagnostic angiography and possible revascularization by PCI when determine is needed. 11

12. Initial Conservative Strategy NSTE-ACS Factors that can prompt a physician to choose an initially conservative treatment strategy: 12

13. Invasive evaluation and revascularization in NSTE-ACS ESC 2018

14. STEMI Reperfusion Treatment Strategies

15. STEMI Fibrinolysis vs Invasive Angiography & PCI 15

16. STEMI Factors Influencing The Choice of Reperfusion Treatment Strategy The choice of reperfusion strategy is strongly influenced by the local EMS i.e. : Whether the patient is transported to a PCI-capable vs. Non-PCI-capable hospital

17. STEMI Reperfusion Treatment Strategies ESC 2017

18. STEMI Reperfusion Treatment Strategies ESC 2017

19. Reperfusion Therapy for Patts with STEMI * Cardiogenic shock or severe HF patients initially seen at non–PCI-center should be transferred to PCI center ASAP, irrespective of time delay from MI onset (Class I, LOE: B). US GL 2013 STEMI The US Guidelines or Reperfusion Therapy

20. STEMI Contraindications for Fibrinolysis  Hemorrhage is the most important risk of fibrinolytic therapy  Certain patients with bleeding risks are contraindicated for fibrinolysis 20

21. PCI After Fibrinolysis 21 PCI after fibrinolysis is indicated when: There is objective evidence of recurrent MI Moderate or severe spontaneous or provocable myocardial ischemia during recovery from STEMI Persistent evidence of ongoing ischemia Cardiogenic shock or hemodynamic instability

22. STEMI ESC 2017 Reperfusion Treatment Strategies of IRA

23. STEMI ESC 2017 Reperfusion Treatment Strategies of IRA

24. STEMI: Primary PCI procedural aspects (strategy and technique) ESC 2018

25. Acute Surgical Reperfusion “CABG” 25 ≈ 10-20% of STEMI patients will be referred for CABG Indication of CABG: Failed PCI in patients with persistent pain or hemodynamic instability Persistent or recurrent ischemia in patients not candidates for PCI or fibrinolysis Life-threatening ventricular arrhythmias in the presence of ≥50% LM stenosis and/or 3VD

26. Antiplatelet Therapy to Support Reperfusion in ACS

28. Why Ticagrelor (Brilinta) is Different? BRI-01-SK-0915-0917-NE

29. Clinical Pharmacology: BRILINTA and Clopidogrel BRILINTAClopidogrel Chemical class CPTPThienopyridine Reversible Inhibition of P2Y 12 receptor YesNo PD variability with CYP2C19 genotype NoYes Mean inhibition of platelet aggregation (IPA) at 30 minutes 41%8% Mean IPA at 2 hours 89%38% Gurbel PA, et al. Circulation. 2009;120:2577–2585. BRILINTA: Summary of Product Characteristics, 2010. PLAVIX ® [package insert]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; 2010.

30. Rapid and Potent Platelet Inhibition BRILINTA Clopidogrel Placebo Time (Hours) *P<0.0001 BRILINTA vs Clopidogrel Loading Dose BRILINTA 180-mg loading dose in Stable CAD patients Clopidogrel 600-mg loading dose in Stable CAD patients * * * * * * Adapted from Gurbel PA, et al. Circulation. 2009;120:2577–2585.

31. PLATO Study PLATelet inhibition and patient Outcomes BRI-01-SK-0915-0917-NE

32. James S, et al. Am Heart J. 2009;157:599-605; Wallentin L, et al. N Engl J Med. 2009;361:1045-1057. PLATO: Study Design Primary endpoint : Composite of CV death, MI or stroke Primary safety: Total major bleeding 6-12 month exposure Mean duration 277 days Clopidogrel 300 mg to 600mg loading dose (unless pretreated), then 75 mg od maintenance Ticagrelor 180 mg loading dose, then 90 mg bid maintenance ACS patients with UA/NSTEMI (moderate-to-high risk) STEMI (if primary PCI) All receiving aspirin (75-100 mg daily); clopidogrel-treated or -naive; randomized within 24 hours of index event ( N=18,624 )

33. Wallentin L, et al. N Engl J Med. 2009;361:1045–1057. PLATO: Primary Efficacy Endpoint (Composite of CV Death, MI, or Stroke) No. at risk Clopidogrel BRILINTA 9,291 9,333 Months After Randomization 8,521 8,628 8,362 8,460 8,1246,650 6,743 5,096 5,161 4,047 4,1478,219 024681012 11 10 9 8 7 6 5 4 3 2 1 0 13 Cumulative Incidence (%) 11.7 Clopidogrel 9.8 BRILINTA 0–30 Days 4.8 5.4 Clopidogrel BRILINTA 0–12 Months RRR 16% P<0.001 RRR 12% P=0.045

36. PLATO : STEMI POPULATION

37. PLATO STE-ACS: Primary efficacy endpoint (Composite of CV Death, MI, or Stroke) 10.8% 9.4% STE-ACS Ticagrelor (n=3752) Clopidogrel (n=3792) HR (95% CI) = 0.87(0.75–1.01) p=0.07 Months after randomisation CV death, MI or stroke (%) ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; STE, ST-segment elevation. Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. [Steg 2010:J–L] Primary endpoint benefit with ticagrelor was consistent with the overall PLATO trial results [Wallentin 2009:J] RRR 13% NE-BRI-SK01-1017

38. PLATO STE-ACS: Cardiovascular Death 4.5% 5.5% Months after randomisation CV death (%) STE-ACS Ticagrelor (n=3752) Clopidogrel (n=3792) HR (95% CI) = 0.83(0.67–1.02) p=0.07 ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; STE, ST-segment elevation. Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. CV death benefit with ticagrelor was consistent with the overall PLATO trial results [Wallentin 2009:J] RRR 17% NE-BRI-SK01-1017

39. PLATO STE-ACS: Major Bleeding 9.0% 9.2% Months after randomisation Major bleeding (%) STE-ACS Ticagrelor (n=3719) Clopidogrel (n=3752) HR (95% CI) = 0.98(0.83–1.14) p=0.76 ACS, acute coronary syndromes; CI, confidence interval; HR, hazard ratio; STE, ST-segment elevation. Steg PG, et al. Circulation 2010;122:2131–2141. [Steg 2010:O,P] Bleeding occurred with similar frequency in the ticagrelor and clopidogrel groups [Steg 2010:O,P] P=NS NE-BRI-SK01-1017

40. PLATO : NSTEMI POPULATION Non Invasive Invasive Management

41. Clop5499501949244768392429992395 Tica5581515250364888405631122417 No. at risk HR 0.83 (95% CI 0.74–0.93), p = 0.0013 Lindholm et al. JACC. 2013;61(10):901-3 PLATO NSTE-ACS Overall: Primary efficacy endpoint (Composite of CV Death, MI, or Stroke) RRR 17%

42. PLATO : NSTEMI Invasive Management

43. C, revasc2676259025472299207515281291 T, revasc2738266526262340211615531312 No. at risk HR 0.86 (95% CI 0.68–1.09) NSTE-ACS Invasive Strategy: Primary efficacy endpoint (Composite of CV Death, MI, or Stroke) ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; STE, ST-segment elevation. Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. RRR 14%

44. NSTE-ACS Invasive Strategy: Cardiovascular Death N=5,648 Hazard Ratio: 0.76 (95% CI, 0.52-1.13) ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; STE, ST-segment elevation. Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. RRR 24%

46. PLATO : NSTEMI Non Invasive Management

47. C, no revasc2571241323622084182913261104 T, no revasc2618246123942142191113981160 No. at risk NSTE-ACS Non-Invasive Primary efficacy endpoint (Composite of CV Death, MI, or Stroke) ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. RRR 15%

48. NSTE-ACS Non-Invasive: Cardiovascular Death ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057. RRR 25% Pi=0.95

49. C, no revasc24591933179216011311955879 T, no revasc24721887174615711299951859 No. at risk HR 1.05 (95% CI 0.88–1.26) HR 1.10 (95% CI 0.84–1.43) NSTE-ACS Non-invasive: Major Bleeding Interaction p = 0.82 ACS, acute coronary syndromes; CI, confidence interval; CV, cardiovascular; HR, hazard ratio; MI, myocardial infarction; Steg PG, et al. Circulation 2010;122:2131–2141; Wallentin L, et al. N Engl J Med 2009;361:1045–1057.

50. Brilinta Indication BRILINTA: Summary of Product Characteristics, 2010. References: 1. BRILIQUE SPC, 2011. 2. Cannon C et al. Lancet. 2010;375:283-293. 3. James S et al. Am Heart J. 2009;157:599-605. 4. James S et al. BMJ. 2011;342:d3527. doi:10.1136=bmj.d3527/. 5. Wallentin L et al. Supplement to N Engl J Med. 2009;361. doi:10.1056/NEJMoa0904327.

51. Dosing and Administration Initial treatment: 180 mg Morning – Take one LOADING Continue treatment: 90 mg twice daily + Aspirin: 75–150 mg once daily MAINTENANCE Two 90-mg tablets Initiate BRILINTA with a loading dose of aspirin. BRILINTA tablet in the morning (AM) Night – Take one BRILINTA tablet in the evening (PM) Take aspirin (either in the morning or night) BRILINTA: Summary of Product Characteristics, 2010. 12 months Treatment

52. The ESC Guidelines Recommendations on DAPT 2017

53. High bleeding risk is considered as an increased risk of spontaneous bleeding during DAPT (PRECISE-DAPT score ≥25)

54. Algorithm for the use of antithrombotic drugs in patients undergoing PCI (ESC 2018)

55. DAPT (ESC 2018) May be continued (COR: IIb) beyond 1 year according to the stent-driven risk

57. NSTE-ACS: Antithrombotics in patients undergoing PCI (ESC 2018)

58. STEMI Antithrombotic treatment in patients undergoing PCI (ESC 2018)

59. The EU Guidelines Antiplatelet Therapy to Support Reperfusion Fibrinolytic Therapy

60. ACC/AHA 2016 Focused Update on Duration of DAPT

63. Ticagrelor, is recommended by the ESC guidelines before (or at least at the time of) PCI and maintained over 12 months, COR and LOE: A. Class I – LOE A B. Class I – LOE B C. Class II – LOE A D. Class II – LOE C Question ?

64. In patients presented with ACS (STEMI / NSTE-ACS) whom underwent PCI & stent with PRECISE-DAPT Score of 32 points. The type and duration of DAPT: A. ASA + Ticagrelor for 12 months B. ASA + Ticagrelor for 6 months C. ASA + Clopidogrel for 12 months D. ASA + Prasugrel for 6 months Question ?

65. Questions?