Multicenter Automatic Defibrillator Implantation Trial II - MADIT-II

Sep 20, 2010
Font Size
A
A
A
Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Boston Scientific Corp., St. Paul, MN
Date Presented:
01/01/2001
Date Updated:
09/20/2010
Original Posted Date:
09/20/2010
References

Description:

The purpose of the study was to evaluate the prophylactic benefit of implantable cardioverter-defibrillator (ICD) placement in patients with coronary artery disease and a left ventricular ejection fraction (LVEF) of ≥30%, who have had at least one myocardial infarction (MI), but require no further risk stratification.

Hypothesis:

An ICD would be associated with a greater reduction in overall mortality at 2 years compared with conventional therapy.

Study Design

  • Randomized
  • Parallel

Patients Enrolled: 1,232
NYHA Class: NYHA class II/III-57% (conventional therapy) and 60% (ICD therapy)
Mean Follow Up: Mean follow-up 20 months, then median follow-up 7.6 years
Female: 16%
Mean Ejection Fraction: Baseline EF 23% in both groups

Patient Populations:

  • Age >21 years
  • Prior MI >1 month
  • LV dysfunction (EF ≤30%) within 3 months

Exclusions:

  • Coronary revascularization within previous 3 months
  • MI within previous month
  • Had an indication approved by the Food and Drug Administration (FDA) for an ICD, including nonsustained ventricular tachycardia, previous cardiac arrest, sustained ventricular tachycardia
  • NYHA class IV
  • Advanced cerebrovascular disease
  • Other life-threatening diseases

Primary Endpoints:

  • All-cause mortality

Secondary Endpoints:

  • Predictability of ICD discharge based on ventricular tachycardia inducibility at electrophysiologic study
  • Usefulness of signal-averaged ECG, heart rate variability, or T-wave alternans in predicting mortality or ICD discharge
  • Cost-effectiveness.
  • Quality of life

Drug/Procedures Used:

ICD placement in a 3(ICD):2(non-ICD) ratio

Concomitant Medications:

Conventional post-MI medications left to the discretion of the patients' physicians

Principal Findings:

The study was stopped early in November 2001 by the Data Safety and Monitoring Board. Mortality was 14.2% in the ICD arm versus 19.8% in the conventional therapy arm (p = 0.016), a 31% relative reduction (hazard ratio 0.69).

Kaplan-Meier estimates of survival show the two groups did not begin to diverge until 9 months, and continued thereafter (p = 0.007). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, EF, New York Heart Association (NYHA) class, and the QRS interval.

Hospitalization for heart failure trended to occur more frequently in patients implanted with an ICD compared with conventional therapy (19.9% vs. 14.9%, p = 0.09).

Over long-term follow-up of 8 years, the ICD arm still had lower all-cause mortality compared with the conventional therapy arm (49% vs. 62%, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.56-0.78, p < 0.001). This corresponded to a number needed to treat of eight patients over 8 years per life saved. This was true of both single-chamber (HR 0.64, 95% CI 0.53-0.78, p < 0.001) and dual-chamber (HR 0.68, 95% CI 0.57-0.83, p < 0.001) ICD devices, as well as between 0-4 (HR 0.61, 95% CI 0.50-0.76, p < 0.001) and 4-8 (HR 0.74, 95% CI 0.57-0.96, p < 0.001), respectively. Of the subgroups assessed, there was benefit irrespective of age, gender, NYHA class, and QRS duration. However, patients who had symptomatic congestive heart failure at the time of trial closure did not seem to derive a benefit from the ICD implantation (HR 0.95, 95% CI 0.69-1.30). 

Interpretation:

ICD implantation was associated with a 31% reduction in overall mortality compared to conventional therapy over an average follow-up period of 2 years. Unlike MADIT I, which demonstrated an early survival benefit with ICD, no mortality reduction was observed until 9 months.

The trend toward higher rates of heart failure may be due to the longer time for heart failure to develop since ICD placement was associated with improved survival, but may also be due to defibrillator shocks resulting in myocardial injury or backup ventricular pacing impairing ventricular function.

Long-term results seem to indicate a continued mortality benefit with ICD implantation in this patient population up to 8 years of follow-up.

References:

Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83.

Goldenberg I, Gillespie J, Moss AJ, et al. Long-term benefit of primary prevention with an implantable cardioverter-defibrillator. An extended 8-Year follow-up study of the Multicenter Automatic Defibrillator Implantation Trial II. Circulation 2010;122:1265-71.

 

Keywords: Coronary Artery Disease, Myocardial Infarction, Kaplan-Meier Estimate, Follow-Up Studies, Heart Failure, Stroke Volume, Ventricular Function, Confidence Intervals, Ventricular Dysfunction, Left, Death, Sudden, Cardiac, Defibrillators, Implantable


< Back to Listings