Sudden death as co-morbidity in Sudden death as co-morbidity in patients following vascular interventionpatients following vascular intervention

Impact of ICD therapyImpact of ICD therapy

Advanced Angioplasty Meeting (BCIS)

London, 16 Jan, 2003

Seah Nisam

Director, Medical Science,

Guidant Corporation

What am I doing here ??

Apr 19, 2023

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.

Apr 19, 2023

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 (n = 196)

MUSTT(n = 704)

MADIT II(n = 1232)

AVID(n = 1016)

Age 63 68 65 65

% Males 92 85 85 80

LVEF 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

MADIT & MUSTT: ICD reduces mortality by > 50%

ICD

Control

Pro

babi

lity

of

Sur

viva

l

MUSTT

MADIT

MUSTT no Tx

MUSTT drug Tx

MADIT “Conventional” Tx

Prystowsky /Nisam (AJC 2000)

Hazard ratio: MADIT 0.46 (p =0.009); MUSTT: 0.49 (p = 0.001)

73%

Secondary Prevention Studies Primary Prevention Studies

0

10

20

30

40

AVID CIDS DUTCHCES

CASH MUSTT MADIT CABG-Patch

MADIT II

Control

ICD

39%

20% 38% 0

54%

51%

ICDs reduce mortality by ~ 40%

31%

in primary prevention as well as in secondary

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?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

Exclusion criteria• Previous cardiac arrest

• Sustained VT

• NYHA Class IV

• CABG or PTCA < 3 months

• CABG or PTCA planned

• Life-threatening diseases

• < 21 years

Inclusion criteria•MI > 4 weeks

•LVEF < 30%

•> 21 years

Geelen & Brugada PACE 1999;22:1132-39

CABG ICD pts.(n = 18)

Other ICD pts. (n = 232)

Daoud et al American Heart Journal 1995;130:277-80

Appropriate ICD discharges in patients post CABG (n = 412)

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

CONV ICD (n=490) (n=742)

percent

Beta-blockers 70 70

ACE inhibitors 72 68

Diuretics 81 76

Digitalis 57 57

Statins 65 71

Amiodarone* 10 13

Antiarrhythmics 2 3

* Principally for control of supraventricular arrhythmias (AF)

MADIT II study overview

• 1232 patients enrolled from 76 centers (75 in

U.S., 5 in Europe), from 7/97 to 11/2001

• MADIT-II eligibility: Prior MI, ejection fraction

< 30%

• No previous cardiac arrest or sustained VT

• Randomization 3:2 ICD:control (for analysis of

secondary endpoints)

• Sponsor: Guidant corporation (unrestricted

grant and ICDs used in study)

R*

ICD (742)

No-ICD (490)

Follow-up

(average ~ 2 y.)

Optimal medical therapy

1232 pts.

*Randomization 3:2 (ICD:Control)

• ICD benefit over and above optimal drug therapy

• ICD benefit similar in all important sub-groups: age, LVEF, NYHA Class, time from MI, etc.

MADIT II showed 31% reduction of total mortality in post-MI patient with depressed LV function

A Moss. NEJM 2002

0%

5%

10%

15%

20%

25%

30%

β-blockers ACE inhibitors CABG ICDsICDs

All-

cau

se

Mo

rtal

ity

27%

20%

11%

31%

Trial:Trial: BHATBHAT SAVESAVE CASSCASS MADIT IIMADIT II

N:N: 38003800 22002200 780780 12321232

P-value:P-value: 0.01 0.01 0.0190.019 n.s.n.s. 0.0160.016

Mortality reduction with ICD in MADIT II is higher than major trials that have changed medical practice

Courtesy A. Moss, 2002

CABG Patch Survival Curves

Main study

Pilot study Hypothesis (Control Group)

40

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

Working Group Report

« 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 »

European Heart Journal (2001) 22, 1074-1081