Download and/or Criterion II

A Randomized Study of the Effects of Defibrillator Implantation
Early after Myocardial Infarction in High-Risk Patients on
Optimal Medical Therapy
Gerhard Steinbeck, D. Andresen, K. Seidl, J. Brachmann,
E. Hoffmann, D. Wojciechowski, Z. Kornacewicz-Jach,
M. Zembala, G. Lupkovics, F. Hofgärtner, A. Lubinski,
K. Wegscheider, M. Rosenqvist, F. Habets, J. Senges
on behalf of the IRIS investigators
Presenter Disclosure
Information
Gerhard Steinbeck, MD
The following relationships exist related to this presentation:
Lecture Fees:
AstraZeneca, Medtronic
Advisory Board: Medtronic
Committees and Investigators
Committees:
• Data and Safety Monitoring Board: A. Hjalmarson (chair), L. Kappenberger, N. Victor
• Steering Committee:
Principal investigators: D. Andresen, J. Senges, G. Steinbeck
Members:
E. Hoffmann, K. Seidl, J. Brachmann, A. Lubinski
• Adverse Event Committee:
M. Rosenqvist (chair), M. Block, W. Schöls, B. Sredniawa
• Data Verification Committee:
U. Dorwarth, F. Gindele, B. Mark
Statistics:
Data Coordination Center:
K. Wegscheider
OSE Oncology Services Europe S.a.r.l. München
Investigators:
AUSTRIA: F. Hintringer, Innsbruck. CZECH REPUBLIC: M. Herold, Prague; J. Kauzner, Prague; M. Pleskot, Kralove. GERMANY: E. Altmann,
Dresden; D. Andresen, Berlin; J. Aring, Leverkusen; G. Baumann, Chemnitz; R. Becker, Heidelberg; S. Behrens, Berlin; H. Blanke, Gelsenkirchen;
C. Bossaller, Gehrden; J. Brachmann, Coburg; B. Cabell, Herrsching; G. Dannberg, Jena; W. Doering (†), München Schwabing; Th. Dorsel,
Warendorf; E. Dünninger, Lichtenfels; H. Duwald, Gronau/Leine; R. Fenzl, Berlin; W. Feth, Rockenhausen; S. Fredersdorf, Regensburg; H. Friedl,
Amberg; H. Glunz, Kaiserslautern; O. Göing, Berlin; L. Griesbach, Kirchberg; B. Hailer, Essen; A. Hartmann, Leipzig; H. Heuer, Dortmund;
F. Hofgärtner, Göppingen; E. Hoffmann, München-Bogenhausen; H. Jenss, Waldshut; W. Jung, Villingen-Schwenningen; J. Isbary, Biberach;
Th. Ittel, Stralsund; B. Kaufmann, Wolfach; C. Kirsch, Salzkotten; G. Liebau, Ludwigsburg; J. Manthey, Bad Friedrichshall; M. Manz, Koblenz;
H. Mudra, München Neuperlach; A. Mügge, Bochum; H. Nebelsieck, Sindelfingen; J. Neuzner, Kassel; H. Odenthal, Rheine; C. Perings, Lünen;
G. Richardt, Bad Segeberg; K. Schmailzl, Neuruppin; B. Schneider, Lübeck; F. Seidel, Kempten-Oberallgäu; J. Senges, Ludwigshafen;
G. Steinbeck, München; C. Stellbrink, Bielefeld Mitte; G. Strupp, Fulda; U. Tebbe, Lippe-Detmold; M. Weber, Dachau; K. Weber, Unna; M. Sigg,
Ravensburg; C. Wolpert, Mannheim; R. Zotz, Herford; R. Zotz, Schwalmstadt. HUNGARY: I. Édes, Debrecen; T. Forster, Szeged; G. Lupkovics,
Zalaegerszeg; B. Merkely, Budapest. P0LAND: A. Cieslinski, Poznan; R. Gil, Warsawa; J. Goch, Lodz; J. Gorny, Olsztyn; W. Kargul, Katowice;
K. Kawecka-Jaszcz, Krakow; A. Kleinrok, Zamosc; C. Kornacewicz-Jach, Szczecin; J. Kubica, Bydgoszcz; M. Kurowski, Szczecin; J. Kuzniar,
Rzeszow; J. Lelakowsky, Krakow; A. Lubinski, Lodz; P. Miekus, Gdynia; W. Musial, Bialystok; G. Opolski, Warsawa; W. Pluta, Opole;
P. Ponikowski, Wroclaw; A. Rynkiewicz, Gdansku; H. Szwed, Warsaw; M. Trusz-Gluza, Katowice; D. Wojciechowski, Warsawa; T. WidomskaCzekajska, Lublin; M. Zembala, Zabrze. RUSSIA: E. Chazov, Moscow; D.
Sponsors: Medtronic Bakken Research Center, AstraZeneca
Background
• All cause mortality and sudden death are highest early
after myocardial infarction
• Guidelines based on randomized trials recommend not
to implant a cardioverter-defibrillator (ICD) within 40 days
after acute myocardial infarction (MI) for primary
prevention of sudden cardiac death
Study Hypothesis
Immediate Risk-Stratification Improves Survival (IRIS) study
High-risk patients after acute MI will show a better survival
when treated early with an ICD compared to patients
receiving optimal medical therapy (OMT) alone
Methods Used for Risk-Stratification
Criterion I
Left ventricular ejection fraction (EF) ≤ 40% on
day 5–31, together with heart rate ≥ 90 beats per
minute (bpm) on the first available
electrocardiogram
and/or
Criterion II
Non-sustained ventricular tachycardia at a
rate ≥ 150 bpm during Holter-ECG on day 5-31
Study Organization
• 1:1 randomized, open-label, investigator-initiated European
multicenter trial
• ICD implantation early after MI
• Optimal acute and long-term medical therapy in both groups
• Follow up ≥ 2 years
• Intention-to-treat analysis
• Primary endpoint:
all cause mortality
• Secondary endpoints:
sudden cardiac death
non-sudden cardiac death
non-cardiac death
Study Flow Diagram
Acute Myocardial Infarction
Registry of 62,944 patients
Exclusion criteria n=26,445
Inclusion criteria not met n=35,188
Eligible day 5-31: n=1,311
No consent: n=409
Criterion I
Criterion II
+
+
88
+
604
+
210
3 Strata:
Randomization: n= 902
Consent not valid n=2
ICD + OMT n=445
Consent not valid n=2
OMT n=453
Enrollment: June ’99 – October 2007
Follow-up: mean 37 months, range 0-106 months
OMT: Optimal Medical Treatment
Baseline Demographic Characteristics I
ICD Group
(N=445)
Characteristic
no.
Male sex
Age (years)
STEMI
Anterior index MI
Heart failure on admission
Prior MI
Atrial fibrillation
Diabetes mellitus *
Left bundle branch block **
Hypertension
Strata
Criterion I only
Criterion II only
Criteria I+II
STEMI
MI
Mean ± SD
ST elevation myocardial infarction
Myocardial infarction
Control Group
(N=453)
%
no.
%
345
62.8
341
282
197
77
60
165
45
296
(77.5)
±10.5
(76.6)
(64.2)
(44.4)
(17.3)
(13.5)
(37.2)
(10.1)
(66.7)
344
62.4
348
300
209
89
61
137
29
300
(75.9)
±10.6
(76.8)
(66.8)
(46.1)
(19.6)
(13.5)
(30.2)
(6.4)
(66.2)
299
99
47
(67.2)
(22.2)
(10.6)
303
109
41
(66.9)
(24.1)
(9.1)
* p = 0.03
** p = 0.05
Baseline Demographic Characteristics II
ICD Group
(N=445)
Characteristic
no.
Left ventricular ejection fraction
%
Control Group
(N=453)
no.
%
34.6
±9.3
34.5
±9.4
Criterion I only
32.2
±6.3
31.9
±6.7
Criterion II only
45.9
±10.8
44.8
±11.0
Criteria I+II
29.6
±7.0
31.4
±6.7
Mean ± SD
Acute medical therapy on admission
Antiplatelets
438
(98.9%)
442
(97.8%)
Beta-Blockers
394
(89.1%)
388
(85.7%)
ACE-inhibitors
361
(81.5%)
373
(82.3%)
279
(62.8)
290
(64.0)
55
(12.4)
50
(11.0)
110
(24.8)
113
(24.9)
Reperfusion
PTCA
Thrombolytic therapy †
None
PTCA
†
Percutaneous transluminal coronary angioplasty
without or with subsequent PTCA
All Cause Mortality
117 deaths
All Cause Mortality
117 deaths
116 deaths
EF ≤ 40%, Heart Rate ≥ 90 bpm
Rapid Non-sustained Ventricular Tachycardia
Hazard Ratios for Death From any Cause
in Sselected Subgroups of Interest I
Hazard Ratios for Death From any Cause
in Selected Subgroups of Interest II
Definition of Sudden Cardiac Death
Cardiac death occurring within minutes after the onset of
acute symptoms,
resulted from a documented cardiac arrhythmia,
or was unwitnessed and occurred unexpectedly and
without recognizable causes (e.g. during sleep)
Non-Sudden Cardiac Death
Cumulative Risk of Sudden Cardiac Death
Cumulative Risk of Sudden Cardiac Death
Sudden Cardiac Death
p=0.049
Month after Randomisation
p=0.001
Month after Randomisation
ICD-related Adverse Events
Death within 30 days after randomization:
9 patients in the ICD group
11 patients in the control group
Clinically significant complications (requiring surgical correction,
hospitalization, or intravenous drug administration) occurred in
65/415 ICD patients (15.7%)
- up to 30 days after implant
in 19 patients
(4.6%)
- during later follow-up
in 48 patients (11.6%)
Summary
In a carefully selected post MI study group with moderately reduced
EF (mean 35%), all cause mortality and sudden cardiac death were
substantial (22.9% and 11.6% at three years, respectively)
Early initiation of ICD therapy did not reduce all cause mortality,
independent of the way of risk-stratification
Sudden cardiac death was reduced by the ICD, which was, however,
counterbalanced by an increase of non-sudden cardiac death, an
observation that deserves further study
Conclusions
During the first month after myocardial
infarction, in an optimally treated high-risk
patient population, ICD implantation does
not offer a survival benefit
Therapy Compliance
415/445 patients in the ICD arm actually received the device
(withdrawal of consent n=14, refusing ICD implant n=11, death prior to implant n=5)
ICD implantation was performed 8.8 ± 14.5 days (mean ± SD) after randomization
During follow-up, according data provided by investigators,
21.4 % of patients received appropriate shocks
8.0 % of patients received inappropriate shocks
ICD explanted or permanently deactivated in 15 patients
In summary: 45 patients in the ICD group did not receive
(or did not continue on) the ICD
39 patients in the control group received an ICD