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
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
Background
In randomized trials of primary angioplasty, mortality was low and superior to thrombolytic therapy
"Door-to-Balloon" times 60-90 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
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.
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)
Baseline Characteristics - Time to Treatment
0-2 h >2-3 >3-4 >4-6 >6-12 >12 P value
No. Pts 2,176 6,353 5,718 5,852 4,680 2,301
Age 58.3 60.2 61.7 63.0 62.9 61.3 <0.00001
Male (%) 80.1 75.1 70.3 66.5 65.5 64.5 <0.00001
DM (%) 11.6 14.1 17.3 19.9 22.7 23.7 <0.00001
Prior MI (%) 17.1 17.5 18.1 17.8 17.4 15.1 0.05
Anterior (%) 41.9 39.4 38.0 38.3 40.7 40.5 0.003
Shock % 4.2 4.3 3.8 3.7 3.0 2.2 <0.00001
Lytic contra 10.9 14.5 18.2 21.2 18.7 12.2 <0.00001
Transferred 2.1 5.1 11.1 16.5 22.7 24.3 <0.00001
Baseline Characteristics - Door to Balloon Time
0-60 61-90 91-120 121-150 151-180 >180 Pvalue
No Pts 2,230 5,732 6,614 4,459 2,625 5,406
Age 60.1 60.3 61.4 62.3 63.0 62.3 <0.00001
Male (%) 76.3 74.2 71.1 68.1 65.7 65.5 <0.00001
Diabetes (%) 13.2 14.1 16.9 19.9 20.8 23.2 <0.00001
Prior MI (%) 15.4 15.5 16.9 18.0 17.1 20.8 <0.00001
Anterior (%) 37.3 37.9 38.2 40.3 43.1 40.6 <0.00001
Card. Shock 4.1 3.1 3.5 4.1 4.6 3.4 0.006
Tlytic contra 10.0 11.7 14.7 18.4 23.3 24.0 <0.00001
Transferred 1.7 2.2 6.2 10.8 17.7 38.4 <0.00001
Multivariate Model of in-hospital Mortality
Characteristic Odds Ratio P value
Systolic BP (per 10mmHg) 0.81 <0.0001
Age (per 10 years) 1.70 <0.0001
Killip class IV 6.27 <0.0001
Heart rate (10 beats/min) 1.18 <0.0001
Anterior MI 1.86 <0.0001
Killip class III 3.08 <0.0001
Killip class II 1.95 <0.0001
Hypercholesterolemia 0.58 <0.0001
Diabetes 1.56 <0.0001
Tlytic contraindication 1.54 <0.0001
Door-to-balloon >180 mins 1.61 0.0003
Door-to-balloon 150-180 mins 1.62 0.0007
Hypertension 1.18 0.005
Prior CHF 1.32 0.008
Door-to-balloon 120-150mins 1.41 0.01
N=27,080
P = 0.0001
NRMI-2: Primary PCI
Time to Treatment vs. Mortality
Door-to-Balloon Time (minutes)
P=NS
0.99
1.17
1.13
1.19
1.07
NRMI-2: Primary PCI
Time-to-Treatment vs. Mortality
N=2,176 6,353 5,718 5,852 4,680 2,301
N=27,080
NRMI-2: Primary PCI
Distribution of Door-to-Balloon times
Door-to-Balloon Time (minutes)
N=27,080
P < 0.00001
NRMI-2: Primary PCI
Door-to-Balloon time vs. Mortality
Door-to-Balloon Time (minutes)
P=0.01
P=0.0007
P=0.0003
P=NS
P=NS
1.14
1.15
1.41
1.62
1.61
N=2,230 5,734 6,616 4,461 2,627 5,412
NRMI-2: Primary PCI
Door-to-Balloon time vs. Mortality
P=0.02
P=0.0005
P=0.004
P=NS
P=NS
1.19
1.22
1.44
1.77
1.54
N=22,483
Primary PCI Door-to-Balloon time vs. Mortality
Thrombolytic Eligible Patients only
P=0.02
P=0.001
P=0.005
P=NS
P=NS
1.19
1.22
1.44
1.77
1.54
N=23,484
Primary PCI Door-to-Balloon time vs. Mortality
Excluding Patients Transferred-in
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 1oPCI
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 consider