Transcript Improved survival with an implanted defibrillator in patients with prior

Sudden death as co-morbidity in
patients following vascular intervention
Impact of ICD therapy
Seah Nisam
Director, Medical Science,
Guidant Corporation
Advanced Angioplasty Meeting (BCIS)
London, 16 Jan, 2003
What am I
doing here ??
Epidemiology of sudden cardiac death
•Sudden cardiac death (SCD) due to coronary artery disease
(CAD) is the single most important cause of death in the
adult population of the industrialized world1
• Incidence in Western Europe (similar to US): 300 000
SCD/Y
• 75-80% due to VT/VF
• 5-10% due to bradyarrhythmias
• Out-of-hospital SCD: 8 per 1000 for males between 60-69
years old and a prior history of heart disease2-5
1Priori
S. European Heart Journal 2001. 2Carveth . Surg 1974. 3Vertesi
L. Can Med Assoc J 1978. 4Bachman JW. JAMA 1986. 5Becker. Ann
Emerg Med 1993.
SCD in Myocardial infarction1
Pre-thrombolytic era: Expected mortality after MI ~ 15% at
2.5 years, with ~75% of all deaths being arrhythmic2
Thrombolytic era:
•Incidence of cardiac deaths after MI ~ 5% at 2.5 years, with
50% being arrhythmic;
• VT/VF without preceding ischemia can be expected in 0.5%
to 2.5 of patients 3,4
In post MI at high risk (EMIAT, CAMIAT, TRACE, DIAMOND-MI,
SWORD), cumulative arrhythmic mortality ~ 5% at 1 Y and 9% at 2y
1Priori
S. European Heart Journal 2001. 2Marcus. AM J Cardiol
1988. 3Statters. Am J Cardiol 1996; 4Hohnloser S. JACC 1999.
Great majority of patients in the large ICD
trials have CAD and previous CABG/PTCA
MADIT
MUSTT
MADIT II
AVID
(n = 196)
(n = 704)
(n = 1232)
(n = 1016)
Age
63
68
65
65
% Males
92
85
85
80
0.26
0.30
0.23
0.32
NYHA II/III (%)
65
64
65
45
Coronary Artery
disease (%)
100
100
100
81
Previous
CABG/PTCA (%)
71
67
57/44
~ 50/?
(of CAD pts)
Mean time post-MI
to enrolment (mos)
27
39
> 36
N/A
LVEF
Probability of Survival
MADIT & MUSTT: ICD reduces
mortality by > 50%
MUSTT
ICD
MADIT
MUSTT no Tx
MUSTT drug Tx
MADIT “Conventional” Tx
Control
Hazard ratio: MADIT 0.46 (p =0.009);
MUSTT: 0.49 (p = 0.001)
Prystowsky /Nisam (AJC 2000)
ICDs reduce mortality by ~ 40%
in primary prevention as well as in secondary
40
73%
30
54%
51%
39%
20%
38%
0
20
31%
Control
ICD
10
0
AVID
CIDS
DUTCH
CES
CASH
Secondary Prevention Studies
MUSTT
MADIT
CABGPatch
MADIT II
Primary Prevention Studies
CABG-Patch trial (n = 900)
• Patients requiring CABG, with LVEF < 0.35,
were randomized at time of CABG to ICD or
no ICD
• Patients had no previous history of sustained
ventricular arrhythmias (VT/VF)
• Only arrhythmia “risk stratifier” was signal
averaged ECG (SAECG)
Why no ICD benefit in CABG-Patch?
• CABG - for patients requiring and amenable to surgery is highly effective against mortality and arrhythmias
– Mortality 30 days post CABG was only 11% in following 2 years
– SAECG (only arrhythmia risk stratifier in CABG-Patch) not a
strong one
– Risk stratification (SAECG and LVEF) measured before CABG
• Of all the ICD studies, the only one enrolling patients
without sustained VT/VF (either spontaneous or
inducible) was CABG-Patch
Main lesson from CABG-Patch study: patients without
sufficient arrhythmia risk do not benefit from ICD therapy
MADIT II – Inclusion/Exclusion Criteria
Inclusion criteria
Exclusion criteria
•MI > 4 weeks
•LVEF < 30%
•> 21 years
•
•
•
•
•
•
•
Previous cardiac arrest
Sustained VT
NYHA Class IV
CABG or PTCA < 3 months
CABG or PTCA planned
Life-threatening diseases
< 21 years
CABG ICD
pts.(n = 18)
Other ICD pts.
(n = 232)
Geelen & Brugada
PACE 1999;22:1132-39
Appropriate ICD discharges in
patients post CABG (n = 412)
Daoud et al American Heart Journal 1995;130:277-80
ACC/AHA/NASPE1 and ESC2 Guidelines
new recommendations for ICD indications
Class IIa
Patients with LV ejection fraction of less than
or equal to 30%, at least one month post
myocardial infarction and three months
post coronary artery revascularization
surgery
1.
Gregaratorios, CIRC Oct 15, 2002
2.
Priori, Eur H J, Jan 2003
Conclusions
• Over 80% of patients receiving ICDs have
previous M.I.
• Nearly all CAD patients undergo CABG or PTCA
before ICD implantation
• High percentage of patients receive ICD shocks
despite revascularization
• ICDs reduce all-cause mortality by ~ 40%
compared to controls in randomized clinical trials
Risk for Sudden death and arrhythmias remains
high despite revascularization, and these patients
receive significant benefits from ICDs
MADIT II medications at last follow-up:
optimal and well-matched for both groups
Beta-blockers
ACE inhibitors
Diuretics
Digitalis
Statins
Amiodarone*
Antiarrhythmics
CONV
ICD
(n=490)
(n=742)
percent
70
72
81
57
65
10
2
70
68
76
57
71
13
3
* Principally for control of supraventricular arrhythmias (AF)
MADIT II study overview
• 1232 patients enrolled from 76 centers (75 in
R
*
ICD
(742)
1232 pts.
U.S., 5 in Europe), from 7/97 to 11/2001
• MADIT-II eligibility: Prior MI, ejection fraction
No-ICD
(490)
< 30%
• No previous cardiac arrest or sustained VT
• Randomization 3:2 ICD:control (for analysis of
Follow-up
secondary endpoints)
(average ~ 2 y.)
Optimal medical
therapy
*Randomization 3:2 (ICD:Control)
• Sponsor: Guidant corporation (unrestricted
grant and ICDs used in study)
MADIT II showed 31% reduction of total mortality in
post-MI patient with depressed LV function
• ICD benefit over and
above optimal drug
therapy
• ICD benefit similar
in all important subgroups: age, LVEF,
NYHA Class, time
from MI, etc.
A Moss. NEJM 2002
Mortality reduction with ICD in MADIT II is higher than
major trials that have changed medical practice
All-cause Mortality
30%
20%
31%
25%
20%
15%
27%
11%
10%
5%
0%
β-blockers
Trial:
N:
P-value:
ACE inhibitors
CABG
ICDs
BHAT
SAVE
CASS
MADIT II
3800
2200
780
1232
0.01
0.019
n.s.
0.016
Courtesy A. Moss, 2002
CABG Patch Survival Curves
Main study
Pilot study
Hypothesis
(Control Group)
40
European Heart Journal (2001) 22, 1074-1081
Working Group Report
Indications for implantable cardioverter
defibrillator (ICD) therapy
Study Group on Guidelines on ICDs of the Working Group on
Arrhythmias and the Working Group on Cardiac Pacing of the
European Society of Cardiology
R.N.W. Hauer (chair), E. Aliot, M. Block, A. Capucci, B. Lüderitz,
M. Santini and P.E. Vardas
« Prophylactic indication:
Non-sustained VT 4 days or more after myocardial infarction
with a left ventricular ejection fraction < 40% and inducible VF
or sustained VT at electrophysiological study »