Time-Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction: Every minute counts Giuseppe De Luca MD, Harry Suryapranata MD, PhD, Jan Paul Ottervanger MD, PhD, and Elliot M Antman MD* On behalf of the Zwolle Myocardial Infarction Study Group Department of Cardiology, ISALA Klinieken, Zwolle, The Netherlands, and *Cardiovascular Division, Brigham and Women’s Hospital, Boston, USA Submitted to Circt 2003 _________________________________________ About 1800 pts Zwolle 7yr 1994-2001 Highly stat sig exp relationship between sx-ballon and 1 yr mortality After adjusting for baseline characteristics every 30 min delay from sx-b--- 8% incr in RR of dying at 1 yr TIME TO REP IS AS IMPORTANT FOR PCI AS IT IS FOR LYSIS
In a cohort of 192,509 patients from 645 National Registry of Myocardial Infarction hospitals, the multivariate adjusted odds of death were the same for fibrinolytic therapy or percutaneous coronary intervention (PCI) when the PCI-related delay was 114 minutes (95% CI, 96-132 minutes; P <.001). In this adjusted analysis, the association of increasing PCI-related delay (increasing door-to-balloon–door-to-needle time), with increasing mortality remained significant ( P <.001). The interaction of treatment with fibrinolytic therapy and door-to-balloon–door-to-needle time was also significant ( P <.001). This suggests that the benefit of one treatment over another varied depending on increasing door-to-balloon–door-to-needle time. Pinto DS, Kirtane AJ, Nallamothu BK, et al. Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation . 2006;114:2019-2025.
Shown here are the primary results of the trial. At both sites where patients were transferred as well as in those sites that did not require transfer, there was a reduction in the composite endpoint of death/recurrent MI and stroke.
Trans 32 min D-B 26 min
Welcome Ask The Experts March 24-27, 2007
<ul><li>Welcome </li></ul><ul><li>Ask The Experts </li></ul><ul><li>March 24-27, 2007 </li></ul><ul><li>New Orleans, LA </li></ul>
Incorporating Patient Risk into Decisions Regarding the Optimal Reperfusion Strategy for ST Elevation MI Duane S. Pinto, MD Assistant Professor of Medicine Harvard Medical School Director, Cardiology Fellowship Training Program Beth Israel Deaconess Medical Center Boston, MA
PCI vs Fibrinolysis for STEMI: Short Term Clinical Outcomes PCI Frequency (%) P=0.0002 P=0.0003 P < 0.0001 P < 0.0001 P < 0.0001 P=0.0004 P=0.032 P < 0.0001 Death Death, no SHOCK data ReMI Rec. Ischemia Total Stroke Hem. Stroke Major Bleed Death MI CVA Fibrinolysis N = 7739 Keeley E. et al., Lancet 2003; 361:13-20.
Importance of Rapid Time to Treatment With Fibrinolysis in STEMI Time from onset of symptoms to treatment (hours) Absolute % difference in mortality at 35 days 3.5% 2.5% 1.8% 1.6% 0.5% 0.0 1.0 3.0 2.0 4.0 0 – 1 2 – 3 4 – 6 7 – 12 12 – 24 The Fibrinolytics Therapy Trialists’ collaborative group. Lancet . 1994; 343:311.
NRMI 2: Primary PCI Door-to-Balloon Time vs. Mortality Door-to-Balloon Time (minutes) MV Adjusted Odds of Death P=0.01 P=0.0007 P=0.0003 n = 2,230 5,734 6,616 4,461 2,627 5,412 Cannon CP, JAMA 2000
Symptom – balloon inflation (min) One-year mortality, % 6 RCTs of Primary PCI by Zwolle Group 1994 – 2001 N = 1791 RR = 1.08 for each 30 min delay ( P = 0.04) P < 0.0001 12 10 8 6 4 2 0 0 60 120 180 240 300 360 Symptom Onset-Balloon Time and Mortality in Primary PCI for STEMI DeLuca, Suryapranata, Circ 109:1223, 2004 The relative risk of 1-year mortality increases by 7.5% for each 30-minute delay
Time from Symptom Onset to Treatment Predicts One-year Mortality with PCI p = 0.006 <2 hrs 2-4 hrs 4-6 hrs p = 0.02 De Luca at al, JACC 2003 >6 hrs All Patients Low-Risk p = NS High-Risk
PCI-Related Time Delay vs Mortality Benefit in 22 Randomized Studies of PCI vs Fibrinolytic Therapy Nallamothu and Bates, AJC 2003 23 RCTs For every 10 min delay to PCI: 1 % reduction in Mortality Difference Between PCI & Lysis N= 7419 p=0.006
PCI-Related Time Delay vs Mortality Benefit in 21 Randomized Studies of PCI vs Fibrinolytic Therapy Betriu A, Massotti M. Am J Cardiol. 2005. 100-101 21 RCTs For every 10 min delay to PCI: 0.24 % reduction in Mortality Difference Between PCI & Lysis N= 7350
PCAT-2 Analysis <ul><li>Patient level data included in analysis of 22 trials (n=6,763) </li></ul><ul><li>PPCI was associated with a </li></ul><ul><ul><ul><li>67% reduction in odds of death at 30 days if PCI related delay was <35 minutes </li></ul></ul></ul><ul><ul><ul><li>Only 28% if >35 minutes (p=0.004) </li></ul></ul></ul>Boersma E. EHJ. 2006; 27: 779-788.
Advantage of PCI Compared With Fibrinolysis Decreases as PCI-Related Delay Increases Pinto DS, et al. Circulation . 2006;114:2019-2025. *Betriu A. Am J Cardiol. 2005; 95:100-101. Odds of Death With Fibrinolysis PCI-Related Delay (door-to-balloon–door-to-needle time), min PCI Better Fibrinolysis Better 2.0 1.5 1.25 1.0 0.8 0.5 60 75 90 105 114 135 150 165 180 Randomized Studies*
PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal (Min) Stratified by Patient Characteristics PCI Related Delay (DB-DN) (Min) 68,716 123,793 125,737 66,772 69,331 123,178 115,293 77,141 192,509 <120 120+ ANT NonAnt 65+ <65 Prehospital Delay (min) Infarct Location Age (years) All Patients P<0.05 for all 2 way comparisons Pinto DS, et al. Circulation . 2006;114:2019-2025.
Meta-analysis of Transfer for PCI vs. Fibrinolysis Dalby M, et al. Circ 2003; 1809 2% beneficial survival rate with PPCI with PCI related time delay of 65 minutes
Transportation= 32 min DANAMI-2 Invasive Referral Invasive Referral Minutes Hospitals Fibrinolysis PCI 26 min 0 60 120 180 240 Door-to-balloon Door-to-needle Door-to-balloon In-door-out-door Prehospital Prehospital Prehospital Door-to-needle Prehospital ↑ Randomization-balloon = 90 min Door-balloon = 93 min 45 min 50 min
Maybe Our Systems Are Not Completely Optimized in the US!
DANAMI vs US AMI: Are We As Quick in the US? Pinto DS, et al. Cardiovascular Reviews and Report. 2003;24:267-276. 0 Median Time (min) DANAMI On-Site Primary PCI DANAMI Transfer Primary PCI US AMI Transfer Primary PCI 90 110 185 50 100 150 200 225 25 75 125 175
Times in Randomized Trials vs. the “Real World” BK Nallamothu, ER Bates, HM Krumholz, et al. Circulation 2005; 761 Median Door to Balloon Time: 180 min Median Door to Door (Transfer) Time: 120 Min Median PCI Hospital DB time: 53 Min <5% of patients had Total DB time <90 Min if a transfer was involved Compare this to the randomized studies with: Total DB times of 90 min , Transport times of 30 min , and PCI hospital DB times of 25 min
PCI-Related Time Delay vs Mortality Benefit in 22 Randomized Studies of PCI vs Fibrinolytic Therapy Nallamothu and Bates, AJC 2003 23 RCTs For every 10 min delay to PCI: 1 % reduction in Mortality Difference Between PCI & Lysis N= 7419 p=0.006 DANAMI: on site PCI 90 DB – 50 DN = 40 min delay DANAMI: with transfer 110 DB – 50 DN = 60 min delay “ USA AMI” with transfer: 171 DB – 32 DN = 139 min delay
Prehospital Delay & Timing of Reperfusion Strategy Equivalence PCI Related Delay (DB-DN) Where PCI and Fibrinolytic Mortality Are Equal (Min) Prehospital Delay (min) 19,517 5,296 9,812 41,774 16,119 20,424 10,614 3,739
Gersh, B. J. et al. JAMA 2005;293:979-986. Hypothetical Construct of the Relationship Among the Duration of Symptoms of Acute MI Before Reperfusion Therapy, Mortality Reduction, and Extent of Myocardial Salvage
Summary <ul><li>Simple rules: </li></ul><ul><ul><li>DB<90 min </li></ul></ul><ul><ul><li>DB-DN <60 min </li></ul></ul><ul><ul><li>DN <30 min </li></ul></ul><ul><ul><li>Transfer all for PCI, etc </li></ul></ul><ul><li>are not enough to determine the optimal reperfusion strategy for all patients in all situations </li></ul>
Summary <ul><li>The clinician must integrate: </li></ul><ul><ul><li>Prehospital Delay </li></ul></ul><ul><ul><li>Anticipated STEMI Risk (age, anterior, inferior, shock) </li></ul></ul><ul><ul><li>Anticipated Risk for ICH </li></ul></ul><ul><ul><li>Anticipated Transfer time/PCI related delay </li></ul></ul>
Summary <ul><li>Fibrinolysis is not unreasonable when </li></ul><ul><ul><li>PCI associated with unacceptable delay (Class I) </li></ul></ul><ul><ul><li>Short time from symptom onset (<1 hr) (Class I) </li></ul></ul><ul><li>Primary PCI is superior to Fibrinolysis in several clinical situations, particularly if: </li></ul><ul><ul><li>Competent personnel involved </li></ul></ul><ul><ul><li>DB times are <90 Min, PCI related Delay Acceptable </li></ul></ul><ul><ul><li>High Risk for Bleeding or Complication from MI </li></ul></ul><ul><ul><li>Late Presentation </li></ul></ul>
Summary <ul><li>The benefits and limitations of Primary PCI should be considered when developing regionalized transfer and community based PCI systems </li></ul><ul><li>Continued work is needed to develop pharmacologic strategies to rapidly, effectively, and safely open closed arteries thereby extending the benefit of PCI to a larger group of patients </li></ul>