Presentation on theme: "ICD FOR PRIMARY PREVENTION EVIDENCE REVIEW"— Presentation transcript:
1 ICD FOR PRIMARY PREVENTION EVIDENCE REVIEW VINOD G V
2 MADIT I (The Multicenter Automatic Defibrillator Implantation Trial) 196 patientsIn NYHA I, II, or III with prior myocardial infarctionLeft ventricular ejection fraction < 0.35Documented episode of asymptomatic unsustained ventricular tachycardiaInducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic studyRandomly assigned to receive an implanted defibrillator (n=95) or conventional medical therapy (n=101)
3 Exclusion criteriaPrevious cardiac arrest or ventricular tachycardia causing syncope that was not associated with an acute myocardial infarctionSymptomatic hypotension while in a stable rhythmMyocardial infarction within the past three weeksPatients who had undergone CABG within the past two months or coronary angioplasty within the past three months
4 Primary endpoint: All cause Mortality Two patient groups (1:1) 1. Conventional Medical Therapy (CMT) 2. CMT + ICDMean follow up 27 monthsPrimary endpoint: All cause MortalityFrom bsci.com – see reference section as well. Picture taken from bsci.com
9 Implantable defibrillator Conventional medical therapy MADIT II: Study Design1232 Patients with prior MI more than 30 days and LVEF < 30% randomized in a 3:2 ratioImplantable defibrillator(n=742)Conventional medical therapy(n=490)All Cause Mortality - Average follow-up of 20 monthsStopped early
11 MADIT II: Mortality Events Non CardiacCardiacArrhythmicNon ArrhythmicConvTherapyICDConvTherapyConvTherapyConvTherapyICDICDICD
12 New or Worsening Heart Failure MADIT II: CHFNew or Worsening Heart FailureP=0.09ConventionalTherapyICD
13 CABG Patch trial — The Coronary Artery Bypass Graft (CABG) Patch trial 900 patients undergoing surgical revascularization for severe CADsignificant LV dysfunction (LVEF <36 percent)A positive signal-averaged electrocardiogramAverage follow-up of 32 monthsThere 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 a difference that was not significant
15 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.
16 MUSTT(Multicentre UnSustained Tachycardia Trial) Inclusion criteriaPatients with coronary artery diseaseLeft ventricular ejection fraction of 40 percent or lessAsymptomatic, unsustained ventricular tachycardia.Patients in whom sustained ventriculartachyarrhythmias were induced byprogrammed stimulation
17 MUSTT 704 patients underwent randomization 351 were assigned to receive electrophysiologically guided therapy353 were assigned to receive no antiarrhythmictherapy.Antiarrhythmic drug in 154 and an ICD in 161.The median follow-up was 39 months
18 ResultsThe 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 therapyAt 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
24 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.
25 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 cardiomyopathyA total of 2521 patientsLVEF ≤35 percentNYHA class II or III HFRandomly assigned to ICD implantation, amiodarone, or placebo.The etiology of cardiomyopathy was ischemic in 52 percent and nonischemic in 48 percent
26 ResultsOverall mortality at five years was significantly reduced with ICD therapy (29 versus 36 percent with placebo, HR 0.77, 95% CI ).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).
32 DINAMIT— The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) Evaluated the role of prophylactic ICD implantation compared to no ICDInclusion criteria674 patients with MI in the preceding 6 to 40 days (mean 18 days)LVEF ≤35 percentReduced heart rate variability or elevated resting heart rate (≥80beats/min).Exclusion criteriaPatients with sustained VT >48 hours post-MI, NYHA class IV HF, or coronary artery bypass grafting (CABG) or three-vessel percutaneous coronary intervention post-MIMean follow-up was 30 months.
33 ResultsThere 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.
37 IRIS trial- Immediate Risk Stratification Improves Survival (IRIS) Enrolled 898 patients .Inclusion criteriaincluded 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/minNonsustained VT at a rate of ≥150 beats/minMean follow-up was 37 months
38 ResultsNo 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 groupThe number of nonsudden cardiac deaths was higher in the ICD arm.
42 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 dischargeICD 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 .
43 Patients with a nonischemic dilated cardiomyopathy LVEF ≤35 percent DEFINITE trial — Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)Patients with a nonischemic dilated cardiomyopathyLVEF ≤35 percentVentricular premature beats or NSVT458 patients were enrolledAll 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
44 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).
46 COMPANION trial — The Comparison Of Medical Therapy, Pacing, And Defibrillation In Heart Failure (COMPANION) trial1520 patientsNYHA class III-IV HFLVEF ≤35 percent who had had a hospitalization for HF within the year prior to enrollmentNearly 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 includedACEI OR ARB in 89 percent, beta blockers in 66 percent, and spironolactone in 55 percent.
47 ResultsAt 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