1 / 42

Primary Angioplasty – The case is not proven: pre-hospital thrombolysis with mandated PCI may be equally effective

Department Academic Cardiology. Department Academic Cardiology. Primary Angioplasty – The case is not proven: pre-hospital thrombolysis with mandated PCI may be equally effective . Tony Gershlick University Hospitals of Leicester UK . TCT 2005.

dulcina
Download Presentation

Primary Angioplasty – The case is not proven: pre-hospital thrombolysis with mandated PCI may be equally effective

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Department Academic Cardiology Department Academic Cardiology Primary Angioplasty – The case is not proven: pre-hospital thrombolysis with mandated PCI may be equally effective Tony Gershlick University Hospitals of Leicester UK TCT 2005

  2. LYTIC MECHANICAL V • The debate is not about alternatives –but about resources, identifying real outcome differences between treatments, trying remain un-polarised, doing best for all patients with AMI i.e strategies applicable to different scenarios • Does the data support the proposal ? • What do Kevin and I agree on? Where are our differences? • In the real world what is important for the AMI patient ? • How good is the PPCI data • How good is real world PPCI (cf trial data) • How robust is the evidence for superiority of PPCI over thrombolysis (?) • How optimal is thrombolysis ? • Are there any trials that can still be done ? PPCI

  3. mission lesions stenting • “To a man with a hammer, - all nails look as though they need pounding” Mark Twain

  4. What do we all agree on ? Relationship of TIMI flow grade to survival5 and 12 year follow up Survival percent P=0.04 100 90 5 5 80 5 70 12 5 12 60 50 12 40 30 20 10 0 TIMI 3 TIMI 2 TIMI 1/0 JACC 1999;34:(1) 62-69

  5. 90 80 70 60 50 40 30 20 10 TIMI GRADE 3 FLOW LYSIS PPCI 100 Adjunctive % TIMI Grade 3 patency @ 90 mins 0 SK tPA Accel Reteplase TNKPA tPA

  6. In the real world what is important for the AMI patient ?TIMI flow/ • How good is the PPCI data • How good is real world PPCI (cf trial data) • How robust is the evidence for superiority of PPCI over thrombolysis • How optimal is thrombolysis ? • Are there any trials that can still be done ? Clinical outcome

  7. Primary angioplasty Thrombolysis Quantitative review of 23 trials of primary angioplasty versus thrombolysis ( n=7739 ) Short-term outcome 15.0% 14.0% 0.0002 < 0.0001 10.0% 9.0% 8.0% 7.0% 7.0% 5.0% 3.0% 2.0% 1.0% 1.0% 0.1% 0.0% Death Re-MI Stroke Haem Any event stroke Keeley, Lancet 2003;361:13

  8. short term death non-fatal AMI death, non fatal MI stroke

  9. Primary PCI for AMI C-PORT - Primary Endpoint Through 6 months Intention to Treat 25 p = 0.03 Accel. t-PA (n=226) PCI (n=225) 19.9 20 Median Door to Needle Time = 46 min Median Door to Balloon Time = 102 min p = 0.04 15 12.4 p = NS % of Patients 10.6 10 7.1 p = NS 6.2 5.3 4.0 5 2.2 0 Combined* Death Reinfarction Disabling Stroke *Primary Endpoint: Death, Reinfarction, or Stroke JAMA 2002; 287:1943-51

  10. Is this evidence to introduce a new strategy ? Issues related to Keeley’s m-a Mortality • 2% absolute difference (p=0.0002) • 1.6% cf fibrin specific (p=0.021) • 1.2% exclude shock (p=0.08) • Size trials (15 < 200 patients) • Variable definition of end points eg re-infarction • Double counting fatal strokes • No blinded validation Other issues And in real life ?

  11. 10.0% Primary angioplasty (n=4939) Alteplase (n=24705) 5.4% 5.2% 5.0% 2.9% 2.5% 1.6% 0.7% 0.0% Death Re-MI Stroke NRMI-2: Primary angioplasty versus thrombolysis P<0.0001 Presentation to alteplase 42 min Presentation to balloon 111 min Tiefenbrunn, JACC 1998;31:1240

  12. TRANSFER

  13. DANAMI-2: transfer for primary PCIvs on-site Alteplase (n=1572) P=0.0003 15.0% 13.7% Primary angioplasty Thrombolysis P=0.35 10.0% P<0.001 8.0% 7.8% 6.6% 6.3% p=0.002 5.0% 2.0% 1.6% 1.1% 0.0% Death Re-MI Stroke Any event Anderson 2003;349:733

  14. TIMI Risk Score N= 1134 Low 0-4 High >5 In-H Lysis 5.6% PPCI 8.0 In-H Lysis 36.2% PPCI 25.3% p=0.02

  15. 15.0% Primary PCI (n=1466) 15.0% Thrombolysis (n=1443) 10.0% 8.9% 8.2% 7.0% 6.7% 5.0% 2.2% 1.8% 1.1% 0.0% Death Re-MI Stroke Any event Transfer for primary PCI vs on-site lyticQuantitative review of 5 trials* P<0.0001 P=0.057 P<0.0001 *LIMI, Prague I & II, Air PAMI, DANAMI-2 Keeley, Lancet 2003;361:13

  16. DANAMI-2 Study • The reduction in re-infarction occurred where only 2.5% of ‘lysed pts in the referring hospitals subsequently received PCI compared with 28% in invasive centres • i.e. Lysed patients were treated conservatively in the referring hospitals • By 30days, 19% ‘lysed pts had PCI and 9% PCI group required repeat PCI • ie Primary PCI reduces the need but a significant number require repeat PCI NEJM 2003;349:733

  17. 20% Transfer for PCI 15.3% Streptokinase 15% 10.0% 10% 7.4% 7.3% 6.8% 6.0% 5% 0% All patients Rx <3hrs of Rx >3hrs of symptoms symptoms Prague-2: Transfer for PCI vson-site thrombolysis in acute MI (n=850) Mortality at 30 days p=0.12 p=0.02 Symptoms to balloon 277 min Symptom to lysis 195 min Planned 1200 patients Widimsky, Eur Heart J 2003;24:94

  18. In the real world what is important for the AMI patient ? TIMI flow/CO • How good is the PPCI data NOT GREAT ! • How good is real world PPCI (cf trial data) Can the trial criteria be achieved • How robust is the evidence for superiority of PPCI over thrombolysis • How optimal is thrombolysis ? • Are there any trials that can still be done ?

  19. 15 10 5 0 -5 0 20 40 60 80 100 23 trials of PCI versus thrombolysis (n=7419) 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 Absolute difference in 4-6 week mortality (%) PCI-related time delay (mins) Circles reflect trial sample size Blue line: weighted meta-regression Nallamothu & Bates, Am J Cardiol 2003;92:824

  20. 2.5 2 1.5 1 0.5 0 0-60 61-90 91-120 121-150 151-180 >180 Door to balloon time (min) Time to angioplasty in 27080 patients with acute myocardial infarction Multivariate adjusted odds of in-hospital mortality (95% CI) * * * p<0.001 Median door to balloon time 116 mins Cannon, JAMA 2000;283:2941

  21. High failure rate with out-of-hours PCI even in high volume centre In 1702 cases • referral centre for 11 hospitals • 48% presented between 1800hrs and 0800hrs • PCI failure rate 6.9% vs. 3.8% p<0.01 • 30d mortality 4.2% vs. 1.9% p< 0.01 Zwolle Group JACC 2003;41:2138

  22. 4278 transfer patients Thrombolysis (IH) can be given 30-60 mins after presentation - 60 min (lysis-PPCI) = 90-120 mins door> 80% lost incremental benefit Nallamothu BK, Bates E R, Herrin J, et al. Times to treatment in transfer patients undergoing primary percutaneous coronary intervention in the US. National Registry of Myocardial Infarction (NRMI)-3/4 Analysis. Circulation 2005; 111:761-767

  23. MINAP Data UK 2004 -6 month 2005

  24. X • In the real world what is important for the AMI patient ? TIMI flow/CO • How good is the PPCI dataNOT GREAT ! • How good is real world PPCI (cf trial data) Can the trial criteria be achieved • Are there any trials that can still be done ? re AMI

  25. Primary PCI in the UK Resource Implications BCS Working Group on Cardiology Workforce Requirements • 2 to 3 pmp additional interventionists for resident shift system or 1-2 pmp for non-resident shift system for Primary PCI • additional 150 interventionists for the UK • 381 SpR’s in UK We would need to train and recruit the entire output from the SpR scheme for 2 years to fill these posts

  26. X • In the real world what is important for the AMI patient ? TIMI flow/CO • How good is the PPCI dataNOT GREAT ! • How good is real world PPCI (cf trial data) Can the trial criteria be achieved • How robust is the evidence for superiority of PPCI over thrombolysis • How optimal is thrombolysis ? • Are there any trials that can still be done ? re AMI

  27. Recurrent MI post Thrombolysis

  28. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.Boersma E, Maas AC, Deckers JW, Simoons ML.Lancet. 1996 Sep 21;348(9030):771-5. Difficult to achieve – can lysis be optimised ?

  29. Pre-hospital thrombolysis:meta-analysis of 6 trials (n=6436) 14 12 10 8 Time (SE) to thrombolysis: 104 (7) min for pre-hospital 162 (16) mins for in-hospital 6 % mortality pre-hospital thrombolysis 4 2 OR 0.83 95% CI 0.70-0.98 0 2 0 4 6 8 10 12 14 % mortality in-hospital thrombolysis Morrison JAMA 2000;283:2686

  30. EAST MIDLANDS AMBULANCE SERVICE UK 8 mins 50 mins 42 mins arrival to needle 34 mins 11 mins

  31. PCI ~ 60 mins ~ 80- 90mins FMC PAIN CALL ?~ 60 mins 40 mins FMC PAIN NEEDLE CALL ~ 20 mins DOOR ?~ 60 mins ~ 30 mins Door to PCI time to compete is ~ 60 mins 11 mins 50 mins

  32. Can we improve the outcome of patients receiving pre-hospital lysis ?

  33. Primary Endpoint:Occluded Artery (or D/MI thru Angio/HD) Odds Ratio 0.64(95% CI 0.53-0.76) 36% Odds Reduction P=0.00000036 0.4 0.6 0.8 1.0 1.2 1.6 n=1752 n=1739 Clopidogrel better Placebo better Clopidogrel Placebo

  34. Hierarchical Analysis at 6 Months Re-Lysis Conservative Rescue -PCI C Death 10.6 9.9 5.6 Re AMI 10.6 8.5 2.1 CVA (ich) 0.7 0.72.1 Severe HF 7.0 7.84.9 The REACT trial in press Gershlick et al

  35. Chest Pain Paramedic D AMI PH Lysis REACT-2 600 mg clopidogrel PPCI Pre-discharge angio (GRACIA) MANDATED RESCUE PCI (REACT) 300 mg clopidogrel 90 min ECG

  36. Primary PCI in the UK Resource Implications BCS Working Group on Cardiology Workforce Requirements • 2 to 3 pmp additional interventionists for resident shift system or 1-2 pmp for non-resident shift system for Primary PCI • additional 150 interventionists for the UK • 381 SpR’s in UK We would need to train and recruit the entire output from the SpR scheme for 2 years to fill these posts

  37. Advantages of Integrated approach • Combines the best of 2 complementary treatments • From the start treatment can be individualised • Lives and myocardium being saved from the start • Emergency PCI required less often (>50% have TIMI 3 flow) • PCI done more safely –more stable patients, patent IRA , better visualisation etc etc

  38. Summary & Conclusions • Case versus Non PPCI is unproven • PPCI only approach is blinkered • Primary PCI may have some advantages if it can be undertaken extremely quickly and within the time frames of the RCT earlier if to compete with PHL ! • PHL with mandated rescue has added advantages of earlier treatment, but must have mandated rescue and pre-hospital discharge assessment built in • ONLY when the appropriate trial has been done can PPCI be considered the optimal treatment of choice considering the changes in logistics required for a whole country – even then there is evidence of failure to meet time lines and serious resource implications • Can we afford to implement a strategy that cannot be delivered and may be no better than a model that suits all PHL + Mandated R-PCI ?

  39. The “Kevins” of the world “The clinical scientist” The problems with the catch-all unselective approach

More Related