Relationship of Time to Treatment and Door-to-Balloon Time to Mortality in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty Christopher

Relationship of Time to Treatment and Relationship of Time to Treatment and Door-to-Balloon Time to Mortality in Door-to-Balloon Time to Mortality in

Patients with Acute Myocardial Patients with Acute Myocardial Infarction Treated with Primary Infarction Treated with Primary

AngioplastyAngioplasty

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 2000 .

BackgroundBackground

• 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


BackgroundBackground

• 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


MethodsMethods

• 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 PlanStatistical 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 - Baseline Characteristics - Time to TreatmentTime to Treatment

0-2 h >2-3 >3-4 >4-6 >6-12 >12 P valueNo. 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 <0.00001Male (%) 80.1 75.1 70.3 66.5 65.5 64.5 <0.00001DM (%) 11.6 14.1 17.3 19.9 22.7 23.7 <0.00001Prior MI (%) 17.1 17.5 18.1 17.8 17.4 15.1 0.05Anterior (%) 41.9 39.4 38.0 38.3 40.7 40.5 0.003Shock % 4.2 4.3 3.8 3.7 3.0 2.2 <0.00001Lytic contra 10.9 14.5 18.2 21.2 18.7 12.2 <0.00001Transferred 2.1 5.1 11.1 16.5 22.7 24.3 <0.00001


Baseline Characteristics - Baseline Characteristics - Door to Balloon TimeDoor to Balloon Time

0-60 61-90 91-120 121-150 151-180 >180 PvalueNo 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 <0.00001Male (%) 76.3 74.2 71.1 68.1 65.7 65.5 <0.00001Diabetes (%) 13.2 14.1 16.9 19.9 20.8 23.2 <0.00001Prior MI (%) 15.4 15.5 16.9 18.0 17.1 20.8 <0.00001Anterior (%) 37.3 37.9 38.2 40.3 43.1 40.6 <0.00001Card. Shock 4.1 3.1 3.5 4.1 4.6 3.4 0.006Tlytic contra 10.0 11.7 14.7 18.4 23.3 24.0 <0.00001Transferred 1.7 2.2 6.2 10.8 17.7 38.4 <0.00001


Multivariate Model of in-hospital MortalityMultivariate Model of in-hospital Mortality

Characteristic Odds Ratio P value

Systolic BP (per 10mmHg) 0.81 <0.0001Age (per 10 years) 1.70 <0.0001Killip class IV 6.27 <0.0001Heart rate (10 beats/min) 1.18 <0.0001Anterior MI 1.86 <0.0001Killip class III 3.08 <0.0001Killip class II 1.95 <0.0001Hypercholesterolemia 0.58 <0.0001Diabetes 1.56 <0.0001Tlytic contraindication 1.54 <0.0001Door-to-balloon >180 mins 1.61 0.0003Door-to-balloon 150-180 mins 1.62 0.0007Hypertension 1.18 0.005Prior CHF 1.32 0.008Door-to-balloon 120-150mins 1.41 0.01


4.9 5.26.5 6.7 6.9

5.5

0

2

4

6

8

10

0-2 >2-3 >3-4 >4-6 >6-12 >12

Mo

rtal

ity

(%)

N=27,080P = 0.0001

N=27,080P = 0.0001

NRMI-2: Primary PCI Time to Treatment vs. Mortality

Door-to-Balloon Time (minutes)


0.2

0.6

1

1.4

1.8

2.2

0 >2-3 >3-4 >4-6 >6-12 >12

Time to Treatment (hours)

MV

Ad

just

ed

Od

ds

of

De

ath

P=NS

0.99 1.17 1.13 1.191.07

NRMI-2: Primary PCI Time-to-Treatment vs. Mortality

N=2,176 6,353 5,718 5,852 4,680 2,301


8.2

21.224.4

16.5

9.7

20.0

0

5

10

15

20

25

30

0-60 61-90 91-120 121-150 151-180 >180

% o

f P

atie

nts

8.2

21.224.4

16.5

9.7

20.0

0

5

10

15

20

25

30

0-60 61-90 91-120 121-150 151-180 >180

% o

f P

atie

nts

N=27,080N=27,080

NRMI-2: Primary PCI Distribution of Door-to-Balloon times



4.2 4.6 5.1

6.7

8.57.9

0

2

4

6

8

10

0-60 61-90 91-120 121-150 151-180 >180

Mo

rtal

ity

(%)

N=27,080P < 0.00001

N=27,080P < 0.00001

NRMI-2: Primary PCI Door-to-Balloon time vs. Mortality



0.2

0.6

1

1.4

1.8

2.2

0-60 61-90 91-120 121-150 151-180 >180


MV

Ad

just

ed

Od

ds

of

De

ath P=0.01 P=0.0007 P=0.0003P=NSP=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


0.2

0.6

1

1.4

1.8

2.2

0-60 61-90 91-120 121-150 151-180 >180


MV

Ad

just

ed

Od

ds

of

De

ath

P=0.02 P=0.0005 P=0.004P=NSP=NS

1.19 1.22

1.44

1.77

1.54

N=22,483

Primary PCI Door-to-Balloon time vs. MortalityThrombolytic Eligible Patients only


0.2

0.6

1

1.4

1.8

2.2

0-60 61-90 91-120 121-150 151-180 >180


MV

Ad

just

ed

Od

ds

of

De

ath

P=0.02 P=0.001 P=0.005P=NSP=NS

1.19 1.221.44

1.771.54

N=23,484

Primary PCI Door-to-Balloon time vs. MortalityExcluding Patients Transferred-in


LimitationsLimitations

• 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 ConclusionsSummary 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


0

0.2

0.4

0.6

0.8

1

1.2

<12 12-36 >36Hospital Volume of Primary Angioplasty

Cases per Year

MV

Ad

just

ed

Od

ds

of

De

ath

NRMI-2: Hospital Volume of Primary PCI vs. Mortality

N=4,740 14,078 8,262

P=0.033

P=0.0001

0.86

0.67

Documents

Relationship of Time to Treatment and Door-to-Balloon Time to Mortality in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty Christopher