Relationship of Time to Treatment and Door-to-Balloon Time to Mortality in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty Christopher P. Cannon, M.D., C. Michael Gibson, M.D., Costas T. Lambrew, M.D., David A. Shoultz, Ph.D., William J. French, M.D., Joel M. Gore, M.D., W. Douglas Weaver, M.D., William J. Rogers, M.D., Alan J. Tiefenbrunn, M.D., for the NRMI-2 Investigators

Cannon CP, et al JAMA: June Background Increasing time to treatment with thrombolysis has been associated with increased mortality Rapid reperfusion -> improved survival Angiographic trials (e.g., GUSTO -I) have shown link between 90 minute, but not 180 minute, patency and improved survival Small differences in time to reperfusion make clinically important differences in survival

Cannon CP, et al JAMA: June Background In randomized trials of primary angioplasty, mortality was low and superior to thrombolytic therapy –"Door-to-Balloon" times mins –Experienced operators In registries, when time delays were greater, mortality higher and not different than thrombolysis –Suggesting that the "door-to-balloon" time may be an important factor in mortality. Prior studies had limited power to evaluate effects of time delays on mortality

Cannon CP, et al JAMA: June Methods NRMI-2 is registry conducted from 6/94 to 3/98 at 1,474 hospitals across the U.S.; 661 perform primary PTCA. Participants in the registry agree to enroll all consecutive MI patients regardless of type, treatment, or outcome. Edit checks on the Case Report Forms are carried out by Data Coordinating Center, and queries sent to the Coordinators for clarification. However, no independent, on-site monitoring of the data is performed.

Cannon CP, et al JAMA: June Statistical Analysis Plan In this pre-specified analysis: –Patients included with primary PTCA as initial reperfusion strategy + ST elevation or new LBBB. Patients were divided into 6 groups by their time -to- treatment and by door-to-balloon time Baseline characteristics compared Univariate and Multivariate analysis was performed Subgroups evaluated (e.g., thrombolytic eligible, cardiogenic shock)

Cannon CP, et al JAMA: June Baseline Characteristics - Time to Treatment 0-2 h >2-3 >3-4>4-6>6-12>12P value No. Pts2,176 6,353 5,7185,8524,6802,301 Age < Male (%) < DM (%) < Prior MI (%) Anterior (%) Shock % < Lytic contra < Transferred <

Cannon CP, et al JAMA: June Baseline Characteristics - Door to Balloon Time >180 Pvalue No Pts2,2305,7326,6144,4592,6255,406 Age < Male (%) < Diabetes (%) < Prior MI (%) < Anterior (%) < Card. Shock Tlytic contra < Transferred <

Cannon CP, et al JAMA: June Multivariate Model of in-hospital Mortality CharacteristicOdds Ratio P value Systolic BP (per 10mmHg)0.81 < Age (per 10 years)1.70< Killip class IV6.27< Heart rate (10 beats/min)1.18< Anterior MI1.86< Killip class III3.08< Killip class II1.95< Hypercholesterolemia0.58< Diabetes1.56< Tlytic contraindication 1.54< Door-to-balloon >180 mins Door-to-balloon mins Hypertension Prior CHF Door-to-balloon mins

Cannon CP, et al JAMA: June N=27,080 P = N=27,080 P = NRMI-2: Primary PCI Time to Treatment vs. Mortality Door-to-Balloon Time (minutes)

Cannon CP, et al JAMA: June P=NS NRMI-2: Primary PCI Time-to-Treatment vs. Mortality N=2,176 6,353 5,718 5,852 4,680 2,301

Cannon CP, et al JAMA: June N=27,080 NRMI-2: Primary PCI Distribution of Door-to-Balloon times Door-to-Balloon Time (minutes)

Cannon CP, et al JAMA: June N=27,080 P < N=27,080 P < NRMI-2: Primary PCI Door-to-Balloon time vs. Mortality Door-to-Balloon Time (minutes)

Cannon CP, et al JAMA: June P=0.01P=0.0007P=0.0003P=NS N=2,230 5,734 6,616 4,461 2,627 5,412 NRMI-2: Primary PCI Door-to-Balloon time vs. Mortality

Cannon CP, et al JAMA: June P=0.02P=0.0005P=0.004P=NS N=22,483 Primary PCI Door-to-Balloon time vs. Mortality Thrombolytic Eligible Patients only

Cannon CP, et al JAMA: June P=0.02P=0.001P=0.005P=NS N=23,484 Primary PCI Door-to-Balloon time vs. Mortality Excluding Patients Transferred-in

Cannon CP, et al JAMA: June Limitations Observational database and Patients not randomized –Caputo showed  D-B time and  mortality No on-site monitoring –But NRMI-2 database validated >95% vs. CCP Most hospitals low-volume centers –Not necessarily indicative of “center of excellence” –Accounting for volume: D-B time assoc. with  mortality –NRMI-2 includes 661 of 1190 (56%) hosp with 1 o PCI

Cannon CP, et al JAMA: June Summary and Conclusions In a cohort over 27,000 Patients at 661 US hospitals, Door to balloon times > 2 hours was –Present in 46 % Patients –Associated with 40-60% increase in adjusted mortality –Association present in pre-specified subgroups MD’s and Healthcare systems should monitor and work to  door-to-balloon time. Door-to-balloon time should be considered when choosing between thrombolysis and Primary PCI

Cannon CP, et al JAMA: June NRMI-2: Hospital Volume of Primary PCI vs. Mortality N=4,740 14,078 8,262 P=0.033 P=