Download Effect of Early Revascularization versus

Effect of Early revascularization versus delayed
revascularization versus medical therapy on
inpatient mortality in patients with non ST elevation
MI in a community hospital Setting
Owais Jeelani ,MBBS
Mentor:Dr.A.Herle,MD,FACC
Background
• Coronary heart disease is the leading cause of death
in the United States, with myocardial infarction a
common manifestation of this disease.
• Of all patients having a myocardial infarction, 25 to
35% die before receiving medical attention, most
often from ventricular fibrillation. For those who
reach a medical facility, the prognosis is
considerably better and has improved over the
years: in-hospital mortality rates fell from 11.2% in
1990 to 9.4% in 1999
Background
• In 2006, approximately 1.2 million Americans
sustained a myocardial infarction. Of these, two
third had a myocardial infarction without STsegment elevation
Background
• Randomized trials have shown that a routine
invasive strategy is beneficial in high-risk
patients with acute coronary syndromes.
Non-ST Elevation ACS
Generally caused by
partially occlusive,
platelet-rich thrombus
Results from cross-linking of
fibrinogen by platelet GP IIbIIIa receptors at sites of plaque
rupture
Unobstructed
lumen
GP IIb-IIIa
platelet
thrombus
fibrinogen
Ruptured
plaque Artery
wall
Background
• In patients with myocardial infarction with ST-segment
elevation, in which the infarct-related artery is usually
occluded and there is ongoing transmural ischemia, it is
well established that the earlier primary percutaneous
coronary intervention can be performed, the lower the
mortality.
• By contrast, in patients with acute coronary syndromes
without ST-segment elevation (including unstable
angina and myocardial infarction), the culprit artery is
often patent, there is usually no ongoing transmural
ischemia, and the patient may have a good response to
initial medical treatment.
Background
• Although meta-analyses of previous
randomized trials that compared an invasive
strategy with a conservative strategy in patients
with acute coronary syndromes have shown a
benefit for an invasive strategy, the timing of
angiography in the invasive-strategy group of
these previous studies ranged from as early as
19 hours after randomization in one large trial
to as late as 96 hours in another large trial.
Invasive vs. Conservative Strategy
for UA/NSTEMI – All Studies
ISAR-COOL
RITA-3
VINO
VANQWISH
TRUCS
MATE
ICTUS
TIMI IIIB
TACTICSTIMI 18
FRISC II
Invasive
Conservative
# Pts: 1140
1674
7018
Background
• Given this wide variation in the timing, there
remains substantial uncertainty regarding the
optimal timing for intervention in such patients.
• Small, randomized trials comparing early
intervention with delayed intervention have
generated conflicting results.
Background
• Although some observational analyses have
suggested that earlier intervention, as compared
with delayed intervention, may reduce events,
others have suggested that outcomes appear to
be similar between the two approaches.
• Also, there has been a suggestion of a hazard
associated with routine early intervention.
Study Objective
• Primary endpoint:
-Is early revascularization better than delayed
revascularization or Medical therapy alone in
reducing in hospital mortality in Patients with
non ST elevation MI in a community care
setting?
Secondary endpoint
• What is the relative mortality of NSTEMI
patients undergoing early revascularization vs
delayed revascularization vs medical therapy
alone?
• What is the relative length of hospital stay in
the three groups studied?
• What percentage of coronary angiography
patients actually underwent intervention (PCI
or CABG)?
Methods
• Retrospective Data Analysis of patients at
Mercy Hospital who have documented non ST
elevation MI from June 2008 to June 2009
• Institutional Review Board approval through
the Catholic Health System
• 383 out of 591 patients reviewed were enrolled
in the study after meeting the inclusion
criteria
Inclusion criteria
• Based on ICD Coding 410.71
• Patients with non ST elevation MI with chest
pain at rest, lasting > 30 minutes and nonresponding to sublingual nitroglycerin tablets in
addition to elevated troponins greater than or
equal to 0.1.
Exclusion criteria
• Patients with ST elevation MI not fulfilling the
above criteria.
• Patients with MI not fulfilling the above
inclusion criteria
Analysis of Data
• Mortality odds ratios used for the comparison
of proportion of deaths in each arm (primary
end point).
• Length of Stay comparison evaluated by mean
number of days along with 95% confidence
interval standard deviations.
• paired t-test with a p-value of <0.05 deemed
statistically significant
BASELINE CHARACTERISTICS
Variable
Early
Delayed
P value
Revascularization Revascularization
Medical
P value
Management 2
63.75
63.64
0.9388
76.87
0.0001
41.93
79.34
0.0001
38.67
0.0001
Previous MI
13.978
19.56
0.3174
21.69
0.3237
Diabetes
30.10
23.36
0.2452
31.13
0.3049
28.8
0.0153
34.90
0.9043
Demographic
Characteristics
Age
Male Sex(%)
Medical history(%)
Ischemic changes on 44.08
EKG
Previous Coronary
Procedure
PCI
9.67
20.10
0.0274
23.58
0.1411
CABG
2.15
3.26
0.7219
2.83
0.7344
BASELINE CHARACTERISTICS
Variable
In Hospital
Medication
Early
Delayed
Revascularization Revascularization
%
P value
Medical
Management
%
P Value*
%
Aspirin
96.774
94.021
0.3968
90.566
0.1547
Clopidogrel
72.043
75.543
0.5613
41.509
0.0001
GPIIb/IIIa Inhibitor
38.709
28.260
0.1007
17.924
0.0074
Heparin/LMW
77.419
77.717
1.0000
74.528
0.5887
B-Blockers
92.473
91.847
0.8156
92.452
1.0000
Anti Coagulation
Statins
83.870
76.086
0.1625
81.13
0.6729
ACE- Inhibitors
78.494
73.913
0.4611
69.811
0.2983
CABG
22.580
20.108
0.6416
-
-
Primary Outcome
Characteristic
Revascul
arized %
Medical
%
Odd’s ratio for event(95%CI)
P-Value for
Interaction
20
2.166
13.207
0.1455 (0.0543 to 0.3897)
0.0001
<65
4
1.515
8.34
0.1692(0.0226 to 1.2646)
0.2143
>65
16
2.758
14.634
0.1655(0.0515 to 0.5318)
0.0020
Female
9
3.488
9.23
0.3315(0.0798 to 1.3776)
0.2163
Male
11
1.621
19.51
0.068(0.0171 to 0.2697)
0.0001
No
5
1.092
4.347
0.2431 (0.0397 to 1.487)
0.2519
Yes
15
4.255
29.729
0.1051(0.0309 to 0.3577)
0.0001
No
6
1.960
6.349
0.295(0.0524 to 1.6601)
Yes
14
1.142
23.25
0.0772(0.0228 to 0.261)
Overall
No of
Patients
Age
Sex
ST segment deviation
More than 3 Risk
Factors
0.3007
0.0001
Results
• Primary End-Point
– There is statistically significant difference in inhospital mortality between patients treated with
revascularization versus patients treated
conservatively.
– This difference is reflected in patients >65 yrs of age.
– There is no statistically significant difference in inhospital mortality in patients younger than 65 yrs.
– There is statistically significant difference in inhospital mortality in males, patients with ischemic
changes on EKG and patients having more than 3
risk factors.
Primary Outcome
Characteristic
No of
Patients
Early
%
Delayed
%
Odd’s ratio for event(95%CI)
6
2.1505
2.1739
0.99 (0.1778 to 5.5012 )
0.9899
<65
2
2.084
1.19
1.766(0.1079 to 28.8922)
0.6862
>65
4
2.23
1
0.734(0.0743 to 7.2639)
0.7914
Female
3
1.85
5.35
0.33(0.0336 to 3.3079)
0.6183
Male
3
2.56
1.369
3.342(0.204 to 54.710)
0.4136
Overall
P-Value for
Interaction
Age
Sex
ST segment deviation
No
2
-
0.90
-
-
Yes
4
4.878
5.6603
0.855(0.1361 to 5.3686)
0.8669
No
4
2.87
3.75
0.754(0.0758 to 7.5213)
0.8100
Yes
2
1.724
0.96
1.807(0.1109 to 29.439)
0.6735
Revascularized
Results
• Primary End-Point
-No statistically significant difference in in-hospital
mortality in patients treated with early revascularization
versus patients treated with delayed vascularization
Secondary Outcome
Variable
Early
Delayed
P value
Revascularization Revascularization
Medical
P value*
Management
Length of Stay
Mean
4.14
Age>65
5.25
6.04
0.0006
7.90
0.0001
5.62
0.6090
7.34
0.0009
5.376
9.293
0.3487
8.490
0.8364
0
1.086
0.5523
0.943
1.0000
6.451
8.895
0.6407
11.320
0.2333
Bleeding
Complications
%
Acute Stroke
%
Acute Renal Failure
%
Results
• Secondary Outcome
– Statistically significant difference in hospital length
of stay in patients treated with re vascularization
versus patients treated conservatively
– Statistically significant difference in hospital length
of stay in patients treated with early
revascularization versus patients treated with
delayed revascularization.
– Statistically significant difference in hospital length
of stay in patients >65 years treated with
revascularization versus patients treated
conservatively.
Conclusion
Revascularization offers benefit in reducing short
term mortality over medical therapy alone
Benefit is more pronounced in elderly high risk
male patients.
Immediate catheterization and intervention does
not offer a benefit over initial medical
stabilization followed by delayed catheterization
and intervention
How are we doing?
• Comparison with Action registry data
Comparative Data with GWTG Action Registry for 2010
Characteristic
2008-2009
%
2010
%
Odd’s ratio for event(95%CI)
P-Value for
Interaction
Nation
Top10%
0.1455 (0.0543 to 0.3897)
0.3571
3.6
Unadjusted Death
5.22
7.0
Risk Adjusted Death
3.63
4.6
0.8483 (0.413 to 1.7425)
0.7151
3.8
8
8
1 (0.36 to 2.778)
1
8
Bleeding Events
Medications
Aspirin
94.2
99
0.1903(0.0649 to 0.5579)
0.0010
99
Clopidogrel
68.76
41
3.1572(2.3307 to 4.2769)
0.0001
59
-
4
Prasugrel
7
Revascularization
overall
Within 24 hrs
55.59
56
0.9603(0.5497 to 1.6775)
1.0000
36
21
12
1.477( 0.9595 to 2.2757)
0.0811
35
24
30
0.7452(0.5374 to 1.0334)
0.0808
54
Catheterization
Within 24 hrs
Thinking outside the box…
References
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1. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial
infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20
2. Mehta SR, Cannon CP, Fox KA, et al. Routine vs selective invasive strategies in patients with acute coronary
syndromes: a collaborative meta-analysis of randomized trials. JAMA 2005; 293:2908-2917. Bavry AA, Kumbhani DJ,
Rassi AN, Bhatt DL, 3.Askari AT. Benefit of early invasive therapy in acute coronary syndromes: a meta-analysis of
contemporary randomized clinical trials. J Am Coll Cardiol 2006;48:1319-1325.
4.Cannon CP, Gibson CM, Lambrew CT, et al. Relationship of symptom-onset-to-balloon time and door-to-balloon time
with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283:2941-2947.
5.Antman EM, Hand M, Armstrong PW, et al. 2007 Focused Update of the ACC/AHA 2004 Guidelines for the
Management of Patients With ST-Elevation Myocardial Infarction: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2008;117:296-329. [Erratum,
Circulation 2008;117(6):e162.]
6.Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary
syndromes. N Engl J Med 1992;326:310-318.
7.Cannon CP, Weintraub WS, Demopoulos LA, et al. Comparison of early invasive and conservative strategies in patients
with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:18791887
8.Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised
multicentre study. Lancet 1999;354:708-715.
9.Fox KA, Poole-Wilson P, Clayton TC, et al. 5-Year outcome of an interventional strategy in non-ST-elevation acute
coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005;366:914-920.
10.Spacek R, Widimsky P, Straka Z, et al. Value of first day angiography/angioplasty in evolving non-ST segment
elevation myocardial infarction: an open multicenter randomized trial. Eur Heart J 2002;23:230-238
11.Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off"
strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA
2003;290:1593-1599.
12.de Winter RJ, Windhausen F, Cornel JH, et al. Early invasive versus selectively invasive management for acute
coronary syndromes. N Engl J Med 2005;353:1095-1104
13.Riezebos RK, Ronner E, Ter Bals E, et al. Immediate versus deferred coronary angioplasty in non-ST-elevation acute
coronary syndromes. Heart 2008 December 22 .
14.Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N
Engl J Med 2009;360:2165-2175.