MADIT II, the Multi-center Autonomic Defibrillator Implantation Trial II stopped early for mortality reduction, has ICD therapy earned its evidence-based credentials?
In a press conference on Nov. 20, 2001 it was announced that the Multi-center Autonomic Defibrillator Implantation Trial II (MADIT II) was stopped early because of a 30% reduction in mortality in patients randomised to receive an implantable defibrillator device. The 4 year multi-centre trial of 1200 patients was terminated early after an independent board observed that the post-MI patients with impaired left ventricular function receiving the implantable defibrillator had improved survival rates compared to those receiving conventional treatment. The MADIT II trial's aim was to test whether an AICD will reduce mortality in high-risk patients with coronary artery disease and left ventricular dysfunction with no arrhythmia entry criteria. The intention was to recruit 1200 patients aged 21-85 years with left ventricular ejection fraction (EF) <or=0.30. Exclusion criteria included myocardial infarction within 1 month, coronary artery bypass graft or percutaneous transluminal coronary angioplasty within 2 months, and any patient already satisfying criteria for receiving an AICD by satisfying the entry criteria for the first MADIT trial. The primary end-point was all-cause mortality. Pre-specified secondary outcomes included non-cardiovascular mortality, sudden death, non-fatal myocardial infarction, fatal myocardial infarction, non-fatal cardiac arrest, fatal cardiac arrest, quality of life, and an economic evaluation. A positive outcome for this trial would be a major step forward both in delineating the indication for AICD therapy but also in guiding routine therapy for patients with impaired left ventricular function as defined by a reduced LVEF. This is not the first positive trial for the AICD approach to preventing sudden deaths due to ventricular tachyarrhythmias. Previous trials (MADIT, MUSST and AVID) have demonstrated that implantable defibrillators improve survival in other patient populations. Under current U.S. Food and Drug Administration (FDA) guidelines restricting the use of AICD therapy to defined patient criteria, 300,000 patients each year in the United States are estimated to be eligible to receive an implantable defibrillator. Guidant was quoted as saying that once the complete study findings of MADIT II are published it plans to submit an application to the FDA that, if approved, could double the population of patients eligible for the implanted devices in the USA, clearly having a major impact on care and its costs for the heart failure and post-MI populations.
Coats
Andrew J S
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000150:complications* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000401:mortality / Q000628:therapy*