1. Presented by: Fahim H. Jafary, M.D., F.A.C.C. Associate Professor of Medicine Aga Khan University Hospital, Karachi March 14, 2008 Primary Percutaneous Coronary Intervention in Acute ST Elevation MI – A Pakistani Perspective

2. Jafary / Aga Khan University Hospital 52 M Presents within 2 h of CP

3. Jafary / Aga Khan University Hospital  In ER – VF Arrest – defibrillated

4. Cardiac Catheterization

7. Jafary / Aga Khan University Hospital Case  55 M, ex smoker  Right thalamic infarct one year ago  Within 2 hours of chest pain

8. Jafary / Aga Khan University Hospital Initial EKG

9. Jafary / Aga Khan University Hospital  Offered primary PTCA –Taken to cath lab

10. Cardiac Catheterization

13. Jafary / Aga Khan University Hospital Case  38 M  Acute IMI  Cath Lab

14. Cardiac Catheterization

17. Jafary / Aga Khan University Hospital Case  69 physician  Acute IMI  Cath Lab

18. Cardiac Catheterization

22. Jafary / Aga Khan University Hospital Terminology SymptomsArrival to Hospital Immediate PCI (Primary)

23. Jafary / Aga Khan University Hospital Terminology SymptomsArrival to Hospital Rescue PCI Thrombolysis Elective PCI Immediate PCI (Primary)

24. Why Ask The Question ?

25. Jafary / Aga Khan University Hospital Why Ask the Question ?  There are limitations of thrombolytic therapy

26. Jafary / Aga Khan University Hospital Acute ST Elevation MI 30 % Thrombolytic Ineligible Limitations of Thrombolytic Therapy Bleeding Issues Late Presentation LBBB Too Old

27. Jafary / Aga Khan University Hospital Limitations of Thrombolytic Therapy Intracranial Hemorrhage

28. Jafary / Aga Khan University Hospital Limitations of Thrombolytic Therapy Mortality Reduction is Time Dependant

30. Jafary / Aga Khan University Hospital Limitations of Thrombolytic Therapy Issues with Coronary Patency

31. Thrombolytic Eligible Acute ST Elevation MI Long Term Patent Artery 100 30

32. Thrombolytic Eligible Acute ST Elevation MI 90 minute Patency TIMI 3 Flow No Residual Stenosis Long Term Patent Artery 100 30 85 57 35 TIMI Flow 0 = no flow 1 = poor flow 2 = intermed 3 = brisk flow

33. Thrombolytic Eligible Acute ST Elevation MI 90 minute Patency TIMI 3 Flow No Residual Stenosis Long Term Patent Artery 100 30 85 57 35 No Reperfusion Residual Stenosis Late Reocclusion

34. Residual Stenosis in Infarct Artery at 90 minutes after Thrombolysis Am J Cardiol 2000;85:1409-1413

35. Jafary / Aga Khan University Hospital Thrombolytic Therapy Limitations Benefits not clear cut in some subsets CABG Cardiogenic Shock Elderly > 75

36. Jafary / Aga Khan University Hospital Thrombolytic Therapy Limitations Less effective in some “high risk” subsets Anterior Wall MI Lundergan et al; GUSTO I Angiographic Investigators; JACC 1998; 32: 648

37. Jafary / Aga Khan University Hospital What does the data tell us ?

38. Jafary / Aga Khan University Hospital

39. Weaver et al. JAMA 1997

40. Jafary / Aga Khan University Hospital Keeley, Lancet 2003;361:13 Short Term Outcome 7.0% 3.0% 1.0% 0.1% 8.0% 9.0% 7.0% 2.0% 1.0% 14.0% 0.0% 5.0% 10.0% 15.0% DeathRe-MIStrokeICHAny event Primary angioplasty Thrombolysis 0.0002< 0.0001 Meta analysis of 23 trials

41. Jafary / Aga Khan University Hospital Improved MORTALITY Higher initial reperfusion rates Lower recurrence of ischemia Less intracranial bleeding TIMI 3 flow better but not ideal Early recurrent ischemia 10-15% Restenosis/Reocclusion at 6 months up to 50% Lessons Learnt from PTCA vs Thrombolytic Trials

42. Jafary / Aga Khan University Hospital What predicts good or bad outcomes after primary PCI ?  Time

43. Jafary / Aga Khan University Hospital 23 trials of PCI versus thrombolysis (n=7419) 0 0 -5 5 5 10 15 0 0 20 40 60 80 100 PCI-related time delay (mins) Absolute difference in 4-6 week mortality (%) Absolute difference in 4-6 week mortality (%) Nallamothu & Bates, Am J Cardiol 2003;92:824 Circles reflect trial sample size Blue line: weighted meta-regression Circles reflect trial sample size Blue line: weighted meta-regression Mean time delay 39.5 mins (SD 22.1, range 7-104) 0.94% decrease in mortality benefit for every 10 min delay, p=0.006 No evidence of benefit if delay >62mins Mean time delay 39.5 mins (SD 22.1, range 7-104) 0.94% decrease in mortality benefit for every 10 min delay, p=0.006 No evidence of benefit if delay >62mins

44. Jafary / Aga Khan University Hospital Time to angioplasty in 27080 patients with acute myocardial infarction Cannon, JAMA 2000;283:2941 Multivariate adjusted odds of in-hospital mortality (95% CI) * * * * * p<0.001 Median door to balloon time 116 mins 0 0 0.5 1 1 1.5 2 2 2.5 0-60 61-90 91-120 121-150 151-180 >180 Door to balloon time (min)

45. Jafary / Aga Khan University Hospital ACC/AHA Guidelines Smith et al. Circulation 2005

46. Jafary / Aga Khan University Hospital What predicts good or bad outcomes after primary PCI ?  Operator experience

47. Jafary / Aga Khan University Hospital ACC/AHA Guidelines Smith et al. Circulation 2005

48. Jafary / Aga Khan University Hospital Aga Khan University Hospital Experience

49. Jafary / Aga Khan University Hospital Results – Baseline Characteristics Jafary, et al. J Invasive Cardiol 2007; 19:417-423

50. Jafary / Aga Khan University Hospital Results – Angiographic & Procedural Characteristics Jafary, et al. J Invasive Cardiol 2007; 19:417-423

51. Jafary / Aga Khan University Hospital Results – Mortality Rate  Overall in-hospital mortality rate – 8.1%

52. Jafary / Aga Khan University Hospital Results – Mortality Rate Jafary, et al. J Invasive Cardiol 2007; 19:417-423

53. Jafary / Aga Khan University Hospital Results – Survival Jafary, et al. J Invasive Cardiol 2007; 19:417-423

54. Jafary / Aga Khan University Hospital Predictors of Mortality – Multivariate Analysis Jafary, et al. J Invasive Cardiol 2007; 19:417-423

55. Jafary / Aga Khan University Hospital Conclusions  Primary PCI is the treatment of choice for patients presenting with acute STEMI based on good randomized trials  Limitations: costs, availability  Operator experience and time are extremely important logistical considerations  In the largest series on primary PCI for STEMI from Pakistan Primary PCI for acute STEMI is associated with a high success rate and excellent overall in-hospital survival particularly in the absence of cardiogenic shock.  Independent predictors of in-hospital mortality include age, prior CABG, requirement for intubation, LVEF and cardiogenic shock at presentation.  Our experience suggests that primary PCI is a viable and robust therapeutic option for patients presenting with acute STEMI in Pakistan.

56. Jafary / Aga Khan University Hospital Implications for Pakistan - I  Widespread availability of primary PCI, although vigorously promoted, has yet to become a reality, even in the developed world.  We have shown in the first sizeable report from the Indo-Pakistan subcontinent that primary PCI is a viable therapeutic option and can be performed with excellent results ­despite relatively longer chest pain-to-presentation and door-to-laboratory (surrogate for door-to-balloon) times.  As Pakistan (and India) brace themselves for a cardiovascular epidemic, it is clear that acute STEMI will continue to occur, leading to a loss in productivity. ­The mean age in our study was just under 55 years — an age group that comprises the workforce of any nation.  Although fibrinolytic therapy (almost exclusively streptokinase) is widely available, at least in urban Pakistan, the efficacy of the latter in attaining patency with TIMI 3 flow is, at best, around 50%.

57. Jafary / Aga Khan University Hospital Implications for Pakistan - II  Thus, paradoxically, developing countries like Pakistan need widespread, expensive primary PCI services because such nations cannot afford the burden of lost productivity due to inadequate myocardial salvage.  There is no choice – the state has to fund these programs. ­Preservation of the workforce must be a state priority. ­Cost cutting – reuse wires, guides; cheap bare metal stents ­Involvement of tertiary care hospitals (like AKU) in training operators to do primary PCI ­Drastic cost-cutting measures including  NEED community hospitals to do primary PCI in every nook and corner ……. as opposed to elective PCI ­Elective PCI has NO mortality benefit, primary PCI does

58. Thank You