Transcript ICD PRIMARY PREVENTION 2 _ DR VINOD GV.ppsx

ICD FOR PRIMARY PREVENTION
EVIDENCE REVIEW
VINOD G V
MADIT I (The Multicenter Automatic
Defibrillator Implantation Trial)
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196 patients
In NYHA I, II, or III with prior myocardial infarction
Left ventricular ejection fraction < 0.35
Documented episode of asymptomatic unsustained
ventricular tachycardia
• Inducible, nonsuppressible ventricular tachyarrhythmia
on electrophysiologic study
• Randomly assigned to receive an implanted
defibrillator (n=95) or conventional medical therapy
(n=101)
Exclusion criteria
• Previous cardiac arrest or ventricular tachycardia
causing syncope that was not associated with an
acute myocardial infarction
• Symptomatic hypotension while in a stable
rhythm
• Myocardial infarction within the past three weeks
• Patients who had undergone CABG within the
past two months or coronary angioplasty within
the past three months
Two patient groups (1:1)
1. Conventional Medical Therapy (CMT)
2. CMT + ICD
Mean follow up 27 months
Primary endpoint: All cause Mortality
54% reduction in all cause
mortality in ICD group (p
o.oo9)
No evidence that
amiodarone ,betablockers
had any significant
influence on mortality
curves
MADIT II
MADIT II: Study Design
1232 Patients with prior MI more than 30 days and LVEF < 30% randomized in a 3:2 ratio
Implantable defibrillator
Conventional medical therapy
(n=742)
(n=490)
All Cause Mortality - Average follow-up of 20 months
Stopped early
MADIT II: All-Cause Mortality
Death
25%
20%
Avg. follow-up=20 months
P=0.016
19.8%
15%
Hazard
Ratio =
0.65
14.2%
10%
5%
0%
Conventional
Therapy
ICD
MADIT II: Mortality Events
Non Cardiac
15%
Cardiac
Arrhythmic
Non Arrhythmic
13.7%
10.0%
10%
9.4%
5.5%
5%
0%
4.1%
3.6%
3.5%
Conv ICD
Therapy
Conv
ICD
Therapy
Conv ICD
Therapy
3.7%
Conv ICD
Therapy
MADIT II: CHF
New or Worsening Heart Failure
P=0.09
20%
15%
19.9%
14.9%
10%
5%
0%
Conventional
Therapy
ICD
CABG Patch trial — The Coronary Artery Bypass
Graft (CABG) Patch trial
• 900 patients undergoing surgical
revascularization for severe CAD
• significant LV dysfunction (LVEF <36 percent)
• A positive signal-averaged electrocardiogram
• Average follow-up of 32 months
• There were 101 deaths in the ICD group (71 of
which were cardiac) and 95 in the control group
(72 of which were cardiac). The hazard ratio was
1.07 a difference that was not significant
• Prophylactic therapy with the ICD did reduce
arrhythmic death at 42 months by 45 percent
• Since 71 percent of the deaths in this trial were
nonarrhythmic, the reduction in arrhythmic death did
not impact upon total mortality.
• ICD therapy was unable to improve mortality in this
primary prevention trial because coronary
revascularization itself has such a beneficial effect in
the prevention of sudden death.
MUSTT(Multicentre UnSustained
Tachycardia Trial)
Inclusion criteria
• Patients with coronary artery disease
• Left ventricular ejection fraction of 40 percent or
less
• Asymptomatic, unsustained ventricular
tachycardia.
• Patients in whom sustained ventricular
tachyarrhythmias were induced by
programmed stimulation
MUSTT
• 704 patients underwent randomization
• 351 were assigned to receive
electrophysiologically guided therapy
• 353 were assigned to receive no
antiarrhythmictherapy.
• Antiarrhythmic drug in 154 and an ICD in 161.
• The median follow-up was 39 months
Results
• The two-year (12 versus 18 percent) and five-year (25 versus 32
percent) rates for the primary endpoint were significantly lower for
EPS guided therapy compared to no therapy.
• There was a nearly significant reduction in the secondary endpoint
of total mortality at five years in the group receiving EPS guided
therapy (42 versus 48 percent, p = 0.06).
• The reduction in the primary and secondary endpoints in the EPS
guided group was largely attributable to ICD therapy
• At five years the primary endpoint occurred in 9 percent of those
receiving an ICD compared with 37 percent of those receiving an
antiarrhythmic drug, and the secondary endpoint occurred in 24
and 55 percent respectively.
• There was no difference in outcome between patients receiving no
therapy and those treated with an antiarrhythmic drug
Conclusions
Electrophysiologically guided antiarrhythmic
therapy with implantable defibrillators but
not with antiarrhythmic drugs reduces the risk
of sudden death in high-risk patients with
coronary disease.
SCD-HeFT trial — The Sudden Cardiac Death in
Heart Failure Trial (SCD-HeFT)
Role of an ICD or amiodarone in patients with heart
failure (HF) due to either an ischemic or
nonischemic cardiomyopathy
• A total of 2521 patients
LVEF ≤35 percent
NYHA class II or III HF
• Randomly assigned to ICD implantation,
amiodarone, or placebo.
• The etiology of cardiomyopathy was ischemic in
52 percent and nonischemic in 48 percent
Results
• Overall mortality at five years was significantly reduced
with ICD therapy (29 versus 36 percent with placebo, HR
0.77, 95% CI 0.62-0.96).
• The benefit of an ICD was comparable among patients with
either an ischemic or nonischemic cardiomyopathy.
• Patients with NYHA class III HF did not appear to benefit
from ICD therapy as there was a nonsignificant trend
toward increased mortality in this group (HR 1.16
compared to 0.54 in NYHA class II HF).
• In a post hoc analysis, the benefit of an ICD was seen in
patients with an LVEF ≤30 percent, but not in those with an
LVEF >30 percent (HR 0.73 versus 1.08).
Conclusion
• An ICD is beneficial in patients with HF and a
diminished LVEF (≤35 percent, or perhaps ≤30
percent). In contrast amiodarone was not
beneficial in these patients.
Early post MI trials
• DINAMIT
• IRIS
DINAMIT— The Defibrillator in Acute Myocardial
Infarction Trial (DINAMIT)
Evaluated the role of prophylactic ICD implantation compared to no
ICD
Inclusion criteria
• 674 patients with MI in the preceding 6 to 40 days (mean 18 days)
• LVEF ≤35 percent
• Reduced heart rate variability or elevated resting heart rate
(≥80beats/min).
Exclusion criteria
• Patients with sustained VT >48 hours post-MI, NYHA class IV HF, or
coronary artery bypass grafting (CABG) or three-vessel
percutaneous coronary intervention post-MI
• Mean follow-up was 30 months.
Results
• There was no difference in annual all-cause
mortality between the ICD patients and
controls (7.5 versus 6.9 percent).
• Arrhythmic deaths were more frequent in the
control arm, while nonarrhythmic deaths were
more frequent in the ICD arm.
IRIS trial- Immediate Risk Stratification
Improves Survival (IRIS)
• Enrolled 898 patients .
Inclusion criteria
• included an MI within the preceding 5 to 31 days
and one or both of the following two criteria:
• LVEF ≤40 percent and a resting heart rate
≥90 beats/min
• Nonsustained VT at a rate of ≥150 beats/min
Mean follow-up was 37 months
Results
• No difference in all-cause mortality between
patients randomly assigned to ICD therapy
and those assigned to medical therapy.
• The rate of SCD was higher in the control
group
• The number of nonsudden cardiac deaths was
higher in the ICD arm.
• Significant recovery of ventricular function may have occurred in
some of the patients which would dilute the long-term benefit of
the ICD in such patients.
• Some SCD events in the early postinfarction period may have been
due to recurrent ischemia which would not be definitively treated
by ICD discharge
• ICD implantation might impose additional risk in these patients
immediately post-MI.
• The enrollment requirements of reduced heart rate variability in
DINAMIT and resting heart rate ≥90 beats/minin IRIS could have
selected a group of patients with a high mortality from
nonarrhythmic causes .
DEFINITE trial — Defibrillators in Non-Ischemic
Cardiomyopathy Treatment Evaluation (DEFINITE)
• Patients with a nonischemic dilated
cardiomyopathy
• LVEF ≤35 percent
• Ventricular premature beats or NSVT
• 458 patients were enrolled
• All received standard medical therapy including
an ACE inhibitor (86 percent) and a beta blocker
(85 percent).
• Patients were randomly assigned to an ICD or
medical therapy alone
• There was a trend toward reduction in the primary
endpoint of all-cause mortality in patients treated with an
ICD (7.9 versus 14.1 percent with medical therapy alone,
hazard ratio (HR) 0.65, 95% CI 0.40 to 1.06).
• Among the subset of patients with NYHA class III HF the
difference was significant (HR 0.37, 95% CI 0.15 to 0.90).
• Fewer sudden deaths occurred in the ICD arm, although the
number was very small (three deaths versus 14 deaths in
the medical therapy arm, HR 0.20, 95% CI 0.06 to 0.71).
ICD combined with CRT
COMPANION trial — The Comparison Of Medical
Therapy, Pacing, And Defibrillation In Heart Failure
(COMPANION) trial
• 1520 patients
• NYHA class III-IV HF
• LVEF ≤35 percent who had had a hospitalization for HF
within the year prior to enrollment
• Nearly half of all patients enrolled had a nonischemic
etiology of HF.
Randomly assigned to optimal medical therapy, CRT alone, or
CRT with an ICD.
Medical therapy for HF included
• ACEI OR ARB in 89 percent, beta blockers in 66 percent, and
spironolactone in 55 percent.
Results
• At 12 months there was a significant reduction in
the incidence of the combined endpoint of allcause mortality and all-cause hospitalization in
the two arms receiving CRT compared to the
medical therapy only arm (56 versus 68 percent) .
• The CRT plus ICD arm, but not the CRT only arm,
experienced a significant improvement in the
secondary endpoint of all-cause mortality alone