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Appropriate Use of Lytics: Adherence to the Guidelines Appropriate Use of Lytics: Adherence to the Guidelines W. Frank Peacock, MD, FACEP Vice Chief of Research Department of Emergency Medicine Cleveland Clinic Chagrin Falls, OH

Appropriate Use of Lytics: Adherence to the Guidelines W. Frank Peacock, MD, FACEP Vice Chief Emergency Department The Cleveland Clinic

ST-segment Elevation Spectrum of Acute Coronary Syndromes Ischemic Discomfort at Rest Unstable Angina (UA) Non-Q-wave MI (NSTEMI) Q-wave MI (STEMI) No ST-segment Elevation – ++ + Cardiac Markers Presentation Emergency Department In-hospital 6-24 hours Adapted from Braunwald E, et al. Available at:

Class I Recommendation All STEMI patients should undergo rapid evaluation for reperfusion therapy and have a reperfusion strategy implemented promptly after contact with the medical system. (Level of Evidence: A) Reperfusion Therapy Antman EM, et al. Available at: Accessed November 1, Medical system goal is to facilitate rapid recognition and treatment of patients with STEMI such that door-to-needle (or medical contact–to-needle) time for initiation of fibrinolytic therapy can be achieved within 30 minutes or that door-to- balloon (or medical contact–to-balloon) time for PCI can be kept within 90 minutes.

ED Management

Not critical CDU, d/c? Cath lab?

STEMI: Brief Physical Exam in the Emergency Department Airway, Breathing, Circulation (ABC) Vital signs, general observation Presence or absence of jugular venous distension Pulmonary auscultation for rales Cardiac auscultation for murmurs or gallops Presence or absence of stroke Presence or absence of pulses Presence or absence of systemic hypoperfusion (cool, clammy, pale/ashen) Antman EM, et al. Available at: Accessed November 1, 2005.

STEMI: Acute Medical Therapy General treatment measures Antman EM, et al. Available at: Accessed November 1, Analgesics Nitrates Oxygen β-blockers (decrease heart rate) Primary PCI or coronary thrombolysis (primary PCI preferred after 3 hours) Aspirin ( mg, acute dose) Heparin If PCI: – Clopidogrel – GP IIb/IIIa inhibitors Infarct size limitation Reperfusion Antithrombotic and antiplatelet therapy

Goal of Fibrinolytic Therapy Alone: Open Arteries and Reduce Mortality Ross AM, et al. Circulation. 1998;97: min TIMI Flow Post-fibrinolytic GUSTO-I (STK vs t-PA) Angiographic Investigators: Post-lytic TIMI Flow Predicts Mortality

Pharmacologic Reperfusion Available Resources Class I Recommendations STEMI patients presenting to a facility without the capability for expert, prompt intervention with primary PCI within 90 minutes of first medical contact should undergo fibrinolysis unless contraindicated (Level of Evidence: A) Antman EM, et al. J Am Coll Cardiol. Available at: Accessed November 1, 2005.

STEMI: Transfer Status PTCA NRMI ( ) Door-to-balloon times for primary PTCA patients, by primary transfer status. Gibson, CM Am Heart J 2004;148:S29–33. NRMI 1NRMI 2NRMI 3 NRMI 4 NRMI transfer-in patients NRMI non-transfer-in patients

Nallamothu BK et al. Circulation 2005;111: STEMI: Transfer for PCI NRMI ( ) 4,278 patients Door-to-balloon time% of patients <90 min4.2 <2 h h55.4 >4 h

ACC/AHA STEMI Guidelines: Primary Percutaneous Coronary Intervention Class I Recommendations If immediately available, primary PCI should be performed: –In patients with STEMI (including true posterior MI) or MI with new or presumably new LBBB within 12 hours of symptom onset; –In a timely fashion (balloon inflation within 90 minutes); –By persons skilled in the procedure (>75 PCI procedures per year). The procedure should be supported by: –Experienced personnel; –An appropriate laboratory environment (> 200 PCI procedures per year, of which > 36 are primary PCI for STEMI); and –Cardiac surgery backup. (Level of Evidence: A) Antman EM, et al. J Am Coll Cardiol. Available at:

ACC/AHA STEMI Guidelines: Primary Percutaneous Coronary Intervention Class I Recommendations Level of Evidence: B –Primary PCI should be performed as quickly as possible (goal of medical contact-to-balloon or door-to-balloon time < 90 minutes). –If the symptom duration is within 3 hours and the expected door-to-balloon time minus the expected door-to-needle time is: Within 1 hour, primary PCI is generally preferred. Greater than 1 hour, fibrinolytic therapy (fibrin-specific agents) is generally preferred. –If symptom duration is greater than 3 hours, primary PCI is generally preferred. Antman EM, et al. J Am Coll Cardiol. Available at:

In-hospital Mortality vs Door to Balloon Time Door to Balloon Time (hours) In-hosp Death Rate >3.0 N= 2,322 Brodie BR, JACC 47, 2006 N=384N=493N=750N=673

7 year Mortality vs Door to Balloon Time Door to Balloon Time (hours) 7 year Death Rate >3.0 N= 2,322 Brodie BR, JACC 47, 2006 N=384 N=493N=750N=673

Primary PCI vs Thrombolysis in STEMI: Meta-analysis (23 RCTs, N=7739) Adapted with permission from Keeley EC, et al. Lancet. 2003;361: PCI Thrombolytic therapy Frequency (%) Short-term Outcomes (4-6 weeks) Death P =.0002 Nonfatal MI P <.0001 Recurrent Ischemia P <.0001 Hemor- rhagic Stroke P <.0001 Major Bleed P =.032 Death, Nonfatal Reinfarction, or Stroke P <.0001 Bonferroni correction 6 variables: p <0.0083

PCI-Related Time Delay (door-to-balloon, door to-needle) Circle sizes =sample size of the individual study. Solid line=weighted meta-regression. For every 10 min delay to PCI: 1% reduction in mortality difference vs lytics Nallamothu BK, Bates ER. Am J Cardiol. 2003:92:824 Favors PCI Favors Lysis P = min Absolute Risk Difference in Death (%) Mortality With 1° PCI Vs Time

Valentines Day Massacre Keely EC, Boura JA, Grines CL. Feb 14, 2006, Lancet

PCI vs Faciliated PCI: Meta-analysis 17 STEMI trials Received either –Primary PCI (N=2267) –Facilitated PCI N=2237) Short term outcomes (< 42 days) –Death, CVA, non-fatal re-MI –Urgent TVR, re-bleed Keely EC, Boura JA, Grines CL. Lancet, 2006

Facilitated PCI Meta-analysis f-PCI (%)PCI (%)OR (95% CI) Initial TIMI (2.22, 4.45) Final TIMI (0.88, 1.64) Death (1.01, 1.87) Urgent TVR (1.23, 4.66) ICH0.70.1P= Keely EC, Boura JA, Grines CL. Lancet, 2006

Facilitated PCI Meta-analysis Conclusions “Facilitated PCI offers no benefit over primary PCI and should not be used outside of the context of randomized clinical trials” Furthermore, facilitated interventions with thrombolytic based regimens should be avoided.

Time Dependency?

NRMI 2,3,4 452,544 Reperfusion Eligible STEMI Patients 1963 Hospitals Transfer Out Patients n=119,235 Missing Time Intervals n=13,137 Did Not Receive PCI or Fibrinolytic Therapy as Initial Reperfusion n=89,524 Study Population 192,509 Patients 645 Hospitals 230,648 Patients 1860 Hospitals ≥20 STEMI Patients Treated Treatment of ≥10 Patients With Primary PCI and ≥10 Patients With Fibrinolytic Therapy CM Gibson Pinto DS, et al. Circulation. 2006;114: Implications of Hospital Delays for Selection of Reperfusion Strategy in STEMI

Pre-hospital Delay (Min) <65 years and Anterior Infarction <65 years and Non-anterior Infarction ≥65 years and Anterior Infarction ≥65 years and Non-anterior Infarction min Met goal w/o transfer: 2.6% Met goal w/ transfer: 3.6% (n=19,517 pts; n=269 hospitals) 56 min Met goal w/o transfer: 20.2% Met goal w/ transfer: 17.3% (n=19,517 pts; n=269 hospitals) 109 min Met goal w/o transfer: 94.1% Met goal w/ transfer: 92.8% (n=9,812 pts; n=180 hospitals) 154 min Met goal w/o transfer: 99.8% Met goal w/ transfer: 100.0% ( n=20,424 pts; n=271 hospitals) min Met goal w/o transfer: 7.9% Met goal w/ transfer: 11.9% (n=5,296 pts; n=117 hospitals) 103 min Met goal w/o transfer: 89.1% Met goal w/ transfer: 82.2% (n=16,119 pts; n=244 hospitals) 142 min Met goal w/o transfer: 98.1% Met goal w/ transfer: 97.1% (n=3,739 pts; n=91 hospitals) 183 min Met goal w/o transfer: 100.0% Met goal w/ transfer: 100.0% (n=10,614 pts; n=191 hospitals) Time at Which PCI Loses Superiority in Survival Over Fibrinolysis Varies by Patient Risk CM Gibson Pinto DS, et al. Circulation. 2006;114:

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