PPCI in STEMI Dr Hassan Mhish Interventional Cardiology Consultant Cardiology Fellowship Program Director Prince Salman Heart Center King Fahd Medical City Riyadh, KSA ESC at the 22nd Annual Conference of the Saudi Heart Association February 21th, 2011
Primary PCI vs Thrombolysis in STEMI: Quantitative Analysis (23 RCTs*, N=7739) 25 Short-term outcomes (4 6 wk) 20 P<.0001 PCI Thrombolytic therapy Frequency y, % 15 10 P=.0002 P<.0001 P=.032 P<.0001 5 P<.0001 0 Death Nonfatal MI Recurrent Ischemia Hemorrhagic Stroke *The criterion for time to treatment was 6 h or less in 9 of the trials, 12 h in 13 trials, and up to 36 h in the SHOCK trial. Major Bleed Death, Nonfatal Reinfarction, or Stroke Keeley EC, et al. Lancet. 2003;361:13-20.
Background: 2007 focused update of the ACC/AHA STEMI guidelines
Pathway: Triage and Transfer for PCI (in STEMI) STEMI patient who is a candidate for reperfusion Initially seen at a PCI capable facility Send to Cath Lab for primary PCI (Class I, LOE:A) Prep antithrombotic (anticoagulant plus antiplatelet) regimen Diagnostic angio Transfer for primary PCI (Class I, LOE:A) At PCI facility, evaluate for timing of diagnostic angio Initially seen at a non-pci capable facility HIGH RISK Transfer to a PCI facility is reasonable for early diagnostic angio & possible PCI or CABG (Class IIa, LOE:B), High-risk patients as defined by 2007 Medical PCI CABG STEMI Focused therapy only Update should undergo cath (Class 1: LOE B) 2009 STEMI Focused Update. Appendix 5 Initial Treatment with fibrinolytic therapy (Class 1, LOE:A) NOT HIGH RISK Transfer to a PCI facility may be considered (Class IIb, LOE:C), especially if ischemic symptoms persist and failure to reperfuse is suspected
Clinical Implications Incremental time delays to reperfusion have the greatest t impact on myocardial salvage and survival in the first 2-3 hours and have much less impact after 3 hours. Short DBT impact mortality most in pts presenting early who can be reperfused within the 3 hour window of optimum benefit 100 80 60 40 20 0 Myocardial Salvage % Mortality Reduction % Mortality Reduction % Myocardial Salvage % 0 3 6 9 12 24 Hours Gersh JAMA 2007
Mortality With Primary PCI vs Lysis ath (%) Abs solute Ris sk Differen nce in De 15 10 5 0-5 by Relative Timing i P=.006 62 min Favors PCI Favors Lysis 0 20 40 60 80 100 PCI-Related Time Delay (Door-to-Balloon Minus Door-to-Needle), min Circle sizes=sample size of individual study; solid line=weighted meta-regression. For every 10-minute delay to PCI: 0.94% reduction in mortality difference vs lytics. Nallamothu et al. Am J Cardiol. 2003;92:824-826 (B).
Time vs. In-Hospital Mortality Door to Balloon Time: NRMI 3/4 -hospita al Mortali ity % 8 6 4 2 N = 29,222 P < 0.001 3.0 30 4.2 5.7 7.4 In 0 <= 90 90-120 120-150 > 150 Door-to-Balloon (minutes) McNamara RL, et al. JACC. 2006;47:2180.
Interhospital Delay in Transfer Patients Door-to-Door Times 15 12.1 ortality (%) 10 6.4 6.2 M 5 3.2 0 < 30" 30 59" 60 89" > 90" De Luca G, et al. Am J Cardiol. 2005;95:1361.
D2B Time And Mortality 2300 Patients Brodie BR, JACC 2006;47:289 High risk = Killip class 3 or 4, age >70, anterior MI
Terkelsen et al, JAMA 2010
Background: Various delays Symptom onset EMS call Arrival at PCI centre PPCI Fieldtriaged to a PCI centre Patient delay Transportation D2B delay delay Health Care System delay Treatment delay Arrival at local hospital Departure from local hospital Arrival at PCI centre PPCI Transferred from local hospitals Patient delay Transportation delay Local hospital delay Interhospital delay Health Care System delay D2B delay Treatment delay
System delay and mortality Kaplan-Meier Cumulative failure estimates Mortality System delay 0.25 0.30.15 0.20 0 Morta ality, % 0.00 0 0.5 05 0.10 0 15 20 1 2 3 4 5 6 Follow-up (years) 1 2 3 4 5 6 Follow-up (years) 181-360 min. 121-180 min. 61-120 min. 0-60 min. Terkelsen et al, JAMA 2010
MANAGEMENT OF STEMI It is not enough that we do our best; sometimes we have to do what is required Sir Winston Churchill
Thrombolysis Golden time: the first 2 hours from symptoms onset DOOR TO NEEDLE TIME LESS THAN 30 MINUTES
Any Role for Facilitated PCI?
Meta-analysis of 17 Trials* Facilitated PCI Event Facilitated PCI (%) PCI (%) P Death 5.0 3.0.04 Reinfarction 30 3.0 20 2.0.006 Urgent TVR 4.0 1.0.010 Major bleeding 7.0 5.0.010 Stroke 1.1 0.3.0008 *Includes 9 GP IIb/IIIa inhibitor trials (n=1148); 6 thrombolytic therapy trials (n=2957); 2 combination therapy trials (n=399). Keeley EC, et al. Lancet. 2006;367:579-588.
Primary PCI: Door to balloon time of 60-90 minutes is essential Is benefit related to time of presentation? Is benefit related to the risk status? What are the risk factors?
1. Time is Myocardium 2. Infarct Size is 100 Outcome duction (%) ortality Red Mo 80 60 40 20 0 D C Extent of Myocardial Salvage B A 0 4 8 12 16 20 24 Time From Symptom Onset to Reperfusion Therapy, h Critical Time-dependent Period Goal: Myocardial Salvage Time-independent independent Period Goal: Open Infarct-Related Artery Gersh BJ, et al. JAMA 2005;293:979.
Cadillac Plus Horizons-AMI CADILLAC N= 2082 HORIZONS-AMI N = 3602 PCI Performed PCI Performed N=2082 N = 3345 Door-to-Balloon Time Data Available N = 1909 Door-to-Balloon Time Data Available N = 2639 Total Study Population PCI Performed and DBT Data Available N = 4548
Impact of Door-to-Balloon Time (90 min) on One Year Mortality All Patients DBT > 90 min 4.3% 3.1% DBT < 90 min Unadjusted HR 0.72 (0.52 0.99) j ( ) p = 0.045
Impact of Door-to-Balloon Time on One Year Mortality Early (< 1.5 hrs) vs Late Presenters Time to Presentation < 1.5 hours Time Time to to Presentation > 1.5 1.5 hoursti HR 0.49 (0.26-0.93) p = 0.029 DBT > 90 DBT < 90 38% 3.8% 1.9% HR 0.86 (0.58-1.28) p = 0.47 DBT DBT > 90 > 90 min DBT < 90 DBT < 90 min 4.6% 4.6% 4.0%
Impact of Door-to-Balloon Time in Early Presenters: Comparison of High and Low Risk Groups (TIMI Risk < 2 vs > 2) Time to Presentation < 1.5 hrs High Risk Low Risk DBT > 90 7.0% DBT < 90 3.7% HR052(0241 0.52 (0.24-1.08) 08) p = 0.08 HR052(014-1 0.52 (0.14 1.89) p = 0.32 DBT > 90 1.5% DBT < 90 0.8%
TRANSFER-AMI Study of pharmacoinvasive strategy 1059 patients with STEMI non-pci-capable hospitals within 12 hrs of symptom onset with 1 high-risk feature Cantor et al. N Eng J Med 2009;360:26.
Recommendations for Triage and Transfer for PCI: *High Risk Definition Defined in TRANSFER-AMI AMI as >2 mmst STsegment elevation in 2 anterior leads or ST elevation at least 1 mm in inferior leads with at least one of the following: systolic blood pressure <100 mm Hg heart rate >100 beats per minute Killip Class II-III >2 mm of ST-segment depression in the anterior leads >1mm of ST elevation in right-sided lead V4 indicative of right ventricular involvement Cantor et al. N Eng J Med 2009;360:26.
TRANSFER-AMI--Design All patients received standard-dose tenecteplase (TNK), ASA, and either UFH or enoxaparin. a pharmaco-invasive strategy (immediate transfer for PCI within 6 hours of fibrinolytic therapy) or to standard treatment after fibrinolytic therapy (included rescue PCI as required for ongoing chest pain and less than 50% resolution of STelevation at 60-90 minutes or hemodynamic instability). Standard treatment patients who did not require rescue PCI remained at the initial hospital for at least 24 hours and coronary angiography within the first 2 weeks encouraged Cantor et al. N Eng J Med 2009;360:26.
TRANSFER-AMI--Design (cont.) Clopidogrel loading (300 mg for patients < 75 years of age, and 75 mg >75 years of age) strongly encouraged in all study patients GP IIb/IIIa receptor antagonists administered at the PCI-capable hospitals according to institutions standard practice Cantor et al. N Eng J Med 2009;360:26.
TRANSFER-AMI: Results Procedures Median time to TNK administration from symptom onset Pharmaco-invasive vs. Standard Treatment Approximately 2 hrs in both groups Median time from 2.8 hrs vs. 32.5 hrs TNK to catheterization Coronary 98.5% vs. 88.7% angiography PCI performed 84.9% vs. 67.4% Cantor et al. N Engl J Med 2009;360:26.
TRANSFER-AMI: Efficacy Kaplan Meier Curves for Primary Endpoint primary end point: composite of death, reinfarction, recurrent ischemia, new or worsening CHF, or shock within 30 days pharmaco-invasive group=11.0% vs. standard treatment group=17.2% 17.2% Cumulative Incidence p=0.004 11.0% Days RR= 0.64, 95 CI% (0.47-0.87) Cantor et al. N Engl J Med 2009;360:26
TRANSFER-AMI--Safety Results Incidence of TIMI major and minor bleeding and GUSTO moderate and severe bleeding was not different between groups There was higher incidence of GUSTO mild bleeding in the pharmaco-invasive group (13.0% compared to 9.0% in the standard treatment group, p=0.036). Cantor et al. N Eng J M 2009;360:26.
TRANSFER-AMI Study Conclusion Following treatment with fibrinolytic therapy in high risk STEMI pts presenting to hospitals without PCIcapability, transfer to a PCI center to undergo coronary angiography and PCI should be initiated immediately without waiting to determine whether reperfusion has occurred. Cantor et al. N Eng J M 2009;360:26.
CARESS-IN-AMI: AMI: inclusion Criteria STEMI patients presenting within 12 hours from symptom onset with one or more of the following high-risk criteria: summation of ST-segment elevation 15 mm in all 12 ECG leads, new left bundle branch block, previous MI, Killip class II or III, and left ventricular ejection fraction <35%
CARESS-IN-AMI: Primary Outcome primary outcome (composite of all cause mortality, reinfarction, & refractory MI within 30 days) occurred significantly less often in the immediate PCI group vs. standard care/rescue PCI group 10.7% 44% 4.4% HR=0.40 (0.21-0.76) Di Mario et al. Lancet 2008;371.
Adjuvant Medical Therapy ASA 300 mg PO Heparin 5000 IV bolus Plavix 300-600 mg PO GpIIb-IIIa IIIa inhibitors?
Source Meta-analysis analysis of Clopidogrel Pretreatment in PCI Clopidogrel No. (%) Placebo MI Before PCI PCI-CURE CURE 2001 47/1313 (3.6) 68/1345 (5.1) CREDO 2002 PCI-CLARITY CLARITY 37/933 (4.0) 57/930 (6.1) Overall 84/2246 (3.7) 125/2275 (5.5) CV Death or MI After PCI to 30 Days PCI-CURE CURE 2001 38/1313 (2.9) 59/1345 (4.4) CREDO 2002 54/9000 (6.0) 65/915 (7.1) PCI-CLARITY CLARITY 31/933 (3.3) 50/930 (5.4) Overall 123/3146 (3.9) 174/3190 (5.5) OR (95% CI) P=.005 P=.004 Sabatine et al. JAMA. 2005;294:1224-1232 (A). 0 0.25 0.5 0.75 1 1.25 Favors Favors No Pretreatment Pretreatment
BRAVE 3: Study design TREATMENT: pre-pci treatment t t with clopidogrel l (600 mg), followed by abciximab vs. placebo INCLUSION: suspected acute MI (ST change or LBBB) within 24 h of symptom onset EXCLUSION: high risk for bleeding, prior stroke,shock, trauma, thrombolytics, hypertension, relevant hematologic deviations 1 OUTCOMES: infarct size, death, stroke, urgent revascularization of affected artery Mehilli et al. Circ. 2009;119:1933-1940
Effects of Abciximab P= 047 0.47 P= 0.40 No significant difference in infarct size or major bleeding Mehilli et al. Circ. 2009;119:1933-1940
Use of Glycoprotein IIb/IIIa Receptor Antagonists in STEMI Modified Recommendation I IIa IIb III It is reasonable to start treatment with glycoprotein gy IIb/IIIa receptor antagonists at the time of primary PCI (with or without stenting) in selected patients with STEMI: abciximab I IIa IIb III tirofiban and eptifibatide
CONCLUSIONS: STEMI patients who present to hospitals with requisite facilities and expertise, PPCI is the preferred strategy. t Fibrinolysis without delay may provide maximal advantage in younger patients at low risk of hemorrhage and mortality presenting earlier (only if the delay to PPCI is beyond the acceptable time frame for that patient), High-risk STEMI patients, except very early STEMI patients without Q waves on the admission ECG, might benefit from PPCI, even when longer delays are unavoidable. Routine but non-emergent invasive strategy after fibrinolytic therapy is not only safe and effective but also the preferred approach.
AMI: special Groups Cardiogenic Shock Large thrombotic burden Late presentation 12-24 hours
Randomized Studies in Cardiogenic Shock Trial Follow-up n/n n/n Relative Risk 95% CI Relative Risk 95% CI Revascularization (PCI/CABG) SHOCK SMASH 1-year 30 days 76/152 22/32 83/149 18/23 0.80 (0.66;0.98) 0.87 (0.66;1.29) Total 103/184 117/172 0.82 (0.70;0.98) Catecholamines SOAP II (CS Subgroup) Glycoprotein IIb/IIIa-Inhibitors PRAGUE-7 NO Synthase Inhibitors TRIUMPH SHOCK-2 Cotter et al Total 28 days 64/145 50/135 Early revascularization better Norepinephrine better Medical treatment better Dopamine better 0.75 (0.55;0.93) In-hospital 15/40 13/40 1.15 (0.59;2.27) Up-stream Abciximab better Standard treatment better 30 days 97/201 76/180 1.1414 (0.91;1.45) 30 days 30 days 24/59 4/15 125/275 7/20 10/15 93/215 IABP IABP-SHOCK I 30 days 7/19 6/21 NO Synthase inhibition better Placebo better 1.16 (0.59;2.69) 0.40 (0.13;1.05) 1.05 (0.85;1.29) 1.28 (0.45;3.72) LVAD Thiele et al Burkhoff et al Seyfarth et al Total 30 days 9/21 30 days 9/19 30 days 6/13 24/53 9/20 5/14 6/13 20/47 IABP better LVAD better Standard treatment better IABP better 0.95 (0.48;1.90) 1.33 (0.57-3.10) 100(0442 1.00 (0.44-2.29) 29) 1.06 (0.68-1.66) Thiele et al. Eur Heart J 2010;31:1828-1835 00.25 0.50.75 1 1.5 2 2.5 3
TAPAS: 1-Year Results Ti Trial ldesign: Patients t with ST-elevation myocardial infarction were randomized d to thrombus aspiration prior to PCI (n = 535) or standard PCI without aspiration (n = 536) and followed for 1 year. % 8 4 0 (p = 0.042) (p = 0.05) 4.7 7.6 2.2 4.3 Results All-cause mortality: 4.7% vs. 7.6% (p = 0.042), respectively Cardiac death: 3.6% vs. 6.7% (p = 0.02), 02) respectively Reinfarction: 2.2% vs. 4.3% (p = 0.05), respectively Conclusions In earlier presentation of TAPAS, thrombus All-cause mortality Reinfarction Re-infarction aspiration during acute MI improved reperfusion Thrombus aspiration Standard PCI Extended follow-up to 1 year demonstrates that this strategy reduces death and MI Vlaar PJ, et al. Lancet 2008;371:1915-20
FINESSE: Study design Treatment Pre-PCI treatment with ½ -dose lytic plus abciximab, pre-pci abciximab alone, and abciximab at time of PCI Inclusion Suspected acute MI (ST change or LBBB) within 6 h of symptom onset Exclusion Low risk (<60 yo, localized inferior infarct) high risk for bleeding 1 OUTCOMES Death, VF after 48 hours, shock, CHF within 90 days Ellis et al. N Eng J Med. 2008;358:2205-2217. 51
Primary, secondary, and bleeding end points in FINESSE End point Primary PCI (%) Abciximab- facilitated (%) Combination (abciximab/ reteplase)- facilitated (%) p, combination- facilitated vs primary PCI p, combinationfacilitated vs abciximabfacilitated Primary end point* at 90 days >70% ST segment resolution within 60 90 min TIMI major or minor bleeding through discharge or day 7 10.7 10.5 9.8 NS NS 31.0 33.1 43.9 0.003 0.01 6.9 10.1 14.5 <0.001 0.008 *All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock Ellis et al. N Eng J Med. 2008;358:2205-2217 52
OnTIME 2: Study design Acute myocardial infarction diagnosed in ambulance or referral center ASA+600 mg Clopidogrel Placebo Tirofiban * Transportation Angiogram PCI centre Angiogram Tirofiban provisional PCI Tirofiban cont d van t Hof et al. Lancet 2008;372:537-46. 53
OnTIME 2: endpoints Primary Residual ST segment deviation (>3mm) 1 hour after PCI Key Clinical i l Secondary Combined occurrence of death, recurrent MI, urgent TVR or thrombotic bailout at 30 days follow-up Safety (major bleeding) Death at 1 year follow-up 54
On-TIME 2: Results Residual ST Deviation after PCI p=0.003 3.6± 4.6mm 4.8± 6.3mm van t Hof et al. Lancet 2008;372:537-46 55
On-TIME 2: Results Event-free Survival at 30 days Clinical outcome Placebo tirofiban P-value Death/recurrent MI 39/477 33/473 or urgent TVR (8.2%) (7.0%) 0.485 van t Hof et al. Lancet 2008;372:537-46. 56