Clinical Studies and Outcomes

Multicenter Automatic Defibrillator Implantation Trial (MADIT)

An overview of the MADIT^1-3 trial is included below.

Primary Prevention Trial – ICD Defibrillator vs. Antiarrhythmic Drug Treatment in Post-MI Patients

Protocol

Protocol – MADIT Trial

Hypothesis

To study whether, in patients with a previous MI and LV dysfunction, prophylactic therapy with an ICD can improve survival versus treatment with conventional medical therapy (eg, amiodarone, beta-blockers/sotalol and class I antiarrhythmics).

Primary Endpoint

• Total mortality

Secondary Endpoints

• Arrhythmic mortality
• Costs and cost effectiveness

Results

In post-MI patients at a high risk for VT, prophylactic therapy with an ICD reduced overall mortality by 54% and arrhythmic mortality by 75% compared with conventional medical therapy after a mean follow-up of 27 months.

Multicenter Unsustained Tachycardia Trial (MUSTT)

An overvew of the MUSTT^1-3 trial is included below.

Primary Prevention Trial ICD – Defibrillator vs. Antiarrhythmic Drug Treatment in Post-MI Patients

Protocol

Protocol – MUSTT Trial

Hypothesis

Antiarrhythmic therapy guided by EP testing can reduce the risk of arrhythmic death and cardiac arrest in patients with: coronary artery disease, EF ≤ 40%, and asymptomatic nonsustained VT (>3 beats, <30 sec, rate >100 bpm).

Primary Endpoint

• Arrhythmic death or cardiac arrest

Secondary Endpoints

• Total mortality
• Cardiac mortality
• Spontaneous, sustained VT

Results

For post-MI patients with EF ≤ 40%, and asymptomatic nonsustained VT:

• 44% death rate in Registry Patients (non-inducible VT)
• ICD therapy significantly reduced the incidence of death in the patients with inducible VT:
  • Arrhythmic death or cardiac arrest (73% - 76% reduction)
  • Overall mortality (55% - 60% reduction)
• EP-guided pharmacologic antiarrhythmic therapy provides no survival benefit: neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to EP-guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy

Multicenter Automatic Defibrillator Implantation Trial II (MADIT II)

An overview of the MADIT II^1-3 trial is included below.

Primary Prevention Trial – ICD Defibrillator vs. Antiarrhythmic Drug Treatment in Post-MI Patients

Protocol

Protocol – MADIT II Trial

Hypothesis

To study whether, in patients with a previous MI and LV dysfunction, ICD therapy is able to reduce overall mortality assuming:

• Mortality in control = 19%
• Mortality in ICD = 11.8%
• 38% reduction in mortality at 2 years

Primary Endpoint

• All-cause mortality (intention-to-treat analysis)

Secondary Endpoints

• Predictability of ICD discharge based on VT inducibility at EPS
• Usefulness of SAECG, HRV, TWA in predicting mortality or ICD discharge
• Cost-effectiveness
• Quality of life

Results

For post-MI patients with LVEF ≤ 30%

• ICD therapy significantly reduced the incidence of overall mortality by 31%
• ICD therapy provided significant benefit among patients who were on optimal drug therapies

Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)

An overview of the SCD-HeFT¹ trial is included below.

Primary Prevention Trial

Protocol – SCD-HeFT Trial

SCD-HeFT is a placebo-controlled, randomized clinical trial sponsored by the National Heart Lung and Blood Institute of the National Institutes of Health (NIH) to study the use of ICD defibrillators in heart failure patients with an LVEF ≤ 35% who have not experienced a previous life-threatening arrhythmia.

Study

• Objective: Determine if amiodarone and/or ICD defibrillator therapy improves survival compared to placebo
• Patients: 2,521 patients from 148 centers across the US, Canada and New Zealand were assigned to three treatment arms: ICD defibrillator therapy, drug therapy (amiodarone) and a control arm (placebo). All patients suffered from either Class II or III heart failure. Each group also received optimal conventional heart failure therapy (ACE-inhibitors, beta-blockers, etc.)
• Endpoint: All-cause reduction in mortality
• Secondary endpoints: Cause-specific deaths (arrhythmic and non-arrhythmic), quality of life, cost-effectiveness and the effect of T-wave alternans testing

Results

• In NYHA Class II or III, heart failure patients with EF ≤35% on good background drug therapy, the mortality rate for placebo-controlled patients was 7.2% per year over 5 years
• ICD defibrillators decreased mortality by 23%
• Amiodarone, when used as a primary preventive agent, did not improve survival

Significance

• SCD-HeFT results show that ICDs save the lives of people with moderate heart failure and poor heart pumping function, due to their risk of sudden cardiac arrest (SCA)
• Because SCA is responsible for 60 percent of deaths among Americans with heart failure, the findings from the trial also reinforce the importance of receiving ICD therapy as a preventative measure before experiencing an episode of SCA
• Amiodarone, an oral medication previously believed to be the “gold-standard” anti-arrhythmic drug, was shown to be ineffective in preventing sudden cardiac death. This reinforces the fact that defibrillation is the only treatment that can stop a life-threatening heart rhythm once it occurs
• SCD-HeFT is the largest and longest follow-up ICD trial ever conducted. Most previous heart failure ICD trials studied therapy among the most severe heart failure patients and had shorter follow-up periods. SCD-HeFT was designed to look at a broader class of heart failure patients and follow them longer with a control group more than twice the size of any previous heart failure trial
• SCD-HeFT is the latest in a series of major medical studies demonstrating the life-saving benefits of ICDs. The results reinforce evidence from earlier trials, eg, MADIT, MUSTT, and MADIT II, which showed that ICDs significantly cut the risk of death (31–55 percent) in certain groups of heart attack survivors

Sponsors

The National Heart Lung and Blood Institute of the National Institutes of Health (NIH) sponsored the study with funding from Medtronic, Inc. and Wyeth Pharmaceuticals.

Primary Investigators

Gust Bardy, MD, Seattle Institute for Cardiac Research/University of Washington
Kerry Lee, PhD, Duke University College of Medicine
Daniel Mark, MD, Duke University College of Medicine

Antiarrhythmics Versus Implantable Defibrillators (AVID)

An overview of the AVID¹ trial is included below.

Secondary Prevention Trial

Protocol

Protocol – AVID Trial

Hypothesis

To determine whether initial treatment strategy of ICD defibrillator or antiarrhythmic drug therapy results in longer life.

Primary Endpoint

• Total mortality

Secondary Endpoints

• Cost and quality of life

Results

• Study was terminated early due to significant results
• The ICD defibrillator group experienced a 39% reduction in deaths in the first year, with a 27% and 31% reduction in years 2 and 3

"If we apply the results of AVID to the population at risk [350,000], over 1,000 lives would be saved each year in the US."
—Dr. Claude Lenfant,
National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health

Canadian Implantable Defibrillator Study (CIDS)

An overview of the CIDS¹ trial is included below.

Secondary Prevention Trial

Protocol

Protocol – CIDS Trial

Hypothesis

Initial ICD defibrillator therapy will reduce the risk of arrhythmic death compared to amiodarone for patients at high risk for arrhythmic death due to ventricular tachycardia or ventricular fibrillation (VT or VF).

Primary Endpoint

• Total mortality

Results

• The ICD defibrillator group experienced a 20% relative reduction in mortality in 3 years (P=0.14).

Cardiac Arrest Study Hamburg (CASH)

An overview of the CASH¹ trial is included below.

Secondary Prevention Trial

Protocol

Protocol – CASH Trial

Hypothesis

To compare the incidence of recurrence of cardiac arrest, sudden cardiac death, cardiac mortality, and total mortality in patients treated with antiarrhythmic drugs versus ICD defibrillators.

Primary Endpoint

• Total mortality

Secondary Endpoints

• Recurrences of cardiac arrest requiring cardiopulmonary resuscitation
• Recurrences of hemodynamically unstable ventricular tachycardia
• Incidence of drug withdrawal because of adverse effects
• Incidence of heart transplantation requirement

Results

Preliminary results showed that propafenone treatment is less effective than ICD defibrillator treatment; therefore, this arm was suspended. The ICD defibrillator group experienced a 24% relative reduction in mortality with an ICD defibrillator (P=0.081).