ICD FOR PRIMARY PREVENTION EVIDENCE REVIEW VINOD G V.
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Transcript of ICD FOR PRIMARY PREVENTION EVIDENCE REVIEW VINOD G V.
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ICD FOR PRIMARY PREVENTIONEVIDENCE REVIEW
VINOD G V
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MADIT I (The Multicenter Automatic Defibrillator Implantation Trial)
• 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)
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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
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Two patient groups (1:1) 1. Conventional Medical Therapy (CMT) 2. CMT + ICDMean follow up 27 months
Primary endpoint: All cause Mortality
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54% reduction in all cause mortality in ICD group (p o.oo9)No evidence that amiodarone ,betablockers had any significant influence on mortality curves
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MADIT II
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1232 Patients with prior MI more than 30 days and LVEF < 30% randomized in a 3:2 ratio 1232 Patients with prior MI more than 30 days and LVEF < 30% randomized in a 3:2 ratio
Conventional medical therapy
(n=490)
Conventional medical therapy
(n=490)
Implantable defibrillator
(n=742)
Implantable defibrillator
(n=742)
All Cause Mortality - Average follow-up of 20 monthsAll Cause Mortality - Average follow-up of 20 months
Stopped early Stopped early
MADIT II: Study Design
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19.8%
14.2%
0%
5%
10%
15%
20%
25%
ConventionalTherapy
ConventionalTherapy
ICDICD
P=0.016P=0.016
DeathAvg. follow-up=20 months
DeathAvg. follow-up=20 months
MADIT II: All-Cause Mortality
Hazard Ratio =
0.65
Hazard Ratio =
0.65
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MADIT II: Mortality Events
4.1% 3.5%
13.7%
10.0%9.4%
3.6% 3.7%
5.5%
0%
5%
10%
15%
Non CardiacNon Cardiac
ConvTherapy
ConvTherapy
ICDICD
CardiacCardiac
ConvTherapy
ConvTherapy
ICDICD
ArrhythmicArrhythmic Non ArrhythmicNon Arrhythmic
ConvTherapy
ConvTherapy
ICDICD ConvTherapy
ConvTherapy
ICDICD
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14.9%
19.9%
0%
5%
10%
15%
20%
ConventionalTherapy
ConventionalTherapy
ICDICD
P=0.09P=0.09
New or Worsening Heart FailureNew or Worsening Heart FailureMADIT II: CHF
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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
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• 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.
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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
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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
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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
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ConclusionsElectrophysiologically guided antiarrhythmictherapy with implantable defibrillators butnot with antiarrhythmic drugs reduces the risk of sudden death in high-risk patients with coronary disease.
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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
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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).
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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.
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Early post MI trials
• DINAMIT• IRIS
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DINAMIT— The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)
Evaluated the role of prophylactic ICD implantation compared to no ICDInclusion 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.
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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.
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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/minMean follow-up was 37 months
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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.
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• 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 .
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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
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• 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).
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ICD combined with CRT
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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.
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Results
• At 12 months there was a significant reduction in the incidence of the combined endpoint of all-cause 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
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