3Multicenter Automatic Defibrillator Implantation Trial II MADIT IIMulticenter Automatic Defibrillator Implantation Trial IIStatus: Completed in 2001First trial to show the life-saving benefits of ICDs without requiring patients to have a documented history of abnormal heart rhythms
4Design1Patients were randomized into two treatment arms in a 3:2 ratio.Patients in the first arm were treated with conventional drug treatment and also implanted with an ICD.The second group was treated exclusively with conventional drug treatment, as prescribed by the patient's attending physician (control arm).Patients were seen in the follow-up clinic at 1 month after randomization, and then at 3-month intervals until the termination date of the study or death.From bsci.com – see reference section as well.
5Patient PopulationEligible study participants included both male and female patients over 21 years of age that had experienced an MI at least 30 days prior to study enrollment and demonstrated an ejection fraction (EF) < 30%.Some of the exclusion criteria wereprior cardiac arrestsyncope unrelated to an acute MINYHA Class IVCABG or non-CABG revascularization less than 3 months prior to enrollmentuse of antiarrhythmic agents, except for atrial arrhythmiasComorbidity associated with decreased survival for trial duration.76 Centers worldwide71 US5 European1232 patients enrolledTaken from bsci.com
6Clinical RelevanceTo evaluate the effect of prophylactic ICD therapy on survival in patients with prior MI and LV dysfunction.The primary endpoint was death from any causeFirst trial to show the life-saving benefits of ICDs without requiring patients to have a documented history of abnormal heart rhythmsPurpose from BSCI.com
7Results2Mortality over an average follow-up of 20 monthsConventional Group (n=490)ICD Group (n=742)Hazard Ratio (95% CI)P-value19.8 (97)14.2 (105).69 ( )0.01631% reduction in the risk of death at any interval among patients in the defibrillator group as compared with patients in the conventional-therapy groupThe cumulative survival curves represent a decrease in death rates in the defibrillator group (95% confidence limits; P-value) of 12% at 1 year (27 to 40%), 28% at 2 years (4 to 46%), and 29% at 3 years (5 to 46%).From bsci.com – see reference section as well.
8Additional Results – MADIT II 8-Year Data3 Mortality over an average of 7.6 years* post-enrollmentCumulative Probability of Mortality (n=1232)Hazard Ratio (95% CI)p-valueICDNo ICD (Conventional Therapy)0.66 ( )<0.00149%62%34% relative reduction in the risk of death at any interval among patients with a defibrillator as compared with patients without an ICDNumber needed to treat (NNT)8 at 8 years17 at 2 yearsAnalysis showed sustained benefit with primary ICD therapy in the MADIT II study populationFrom bsci.com – see reference section as well.*median
9References1Moss A, Cannom D, Daubert J et al. Multicenter Automatic Defibrillator Implantation Trial II (MADIT II): Design and Clinical Protocol. Ann Noninvasive Electrocardiol 1999;4:83-91.2Moss A, Zareba W, Hall W, et al, for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:3Goldenberg I, Moss A, Hall W, 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; xxxx
10Brief Summary ICD Systems from Boston Scientific CRM ICD Indications and UsageICDs are intended to provide ventricular antitachycardia pacing and ventricular defibrillation for automated treatment of life-threatening ventricular arrhythmias. ICDs with atrial therapies are also intended to provide atrial antitachycardia pacing and atrial defibrillation treatment in patients who have or are at risk of developing atrial tachyarrhythmias.ContraindicationsUse of ICD systems are contraindicated in: Patients whose ventricular tachyarrhythmias may have reversible cause, such as 1) digitalis intoxication, 2) electrolyte imbalance, 3) hypoxia, or 4) sepsis, or whose ventricular tachyarrhythmias have a transient cause, such as 1) acute myocardial infarction, 2) electrocution, or 3) drowning. Patients who have a unipolar pacemaker.WarningsRead the product labeling thoroughly before implanting the pulse generator to avoid damage to the ICD system. Such damage can result in patient injury or death. Program the pulse generator ventricular Tachy Mode to Off during implant, explant or post-mortem procedures to avoid inadvertent high voltage shocks. Always have sterile external and internal defibrillator protection available during implant. If not terminated in a timely fashion, an induced tachyarrhythmia can result in the patient’s death. Ensure that an external defibrillator and medical personnel skilled in cardiopulmonary resuscitation (CPR) are present during post-implant device testing should the patient require external rescue. Patients should seek medical guidance before entering environments that could adversely affect the operation of the active implantable medical device, including areas protected by a warning notice that prevents entry by patients who have a pulse generator. Do not expose a patient to MRI device scanning. Strong magnetic fields may damage the device and cause injury to the patient. Do not subject a patient with an implanted pulse generator to diathermy since diathermy may cause fibrillation, burning of the myocardium, and irreversible damage to the pulse generator because of induced currents. Do not use atrial tracking modes (or an AVT device) in patients with chronic refractory atrial tachyarrhythmias. Tracking of atrial arrhythmias could result in VT or VF. (Applies to dual-chamber devices only.) Do not use this pulse generator with another pulse generator. This combination could cause pulse generator interaction resulting in patient injury or lack of therapy delivery. Do not kink leads. Kinking leads may cause additional stress on the leads, possibly resulting in lead fracture. For specific models, when using a subpectoral implantation, place the pulse generator with the serial number facing away from the ribs. Implanting the pulse generator subpectorally with the serial number facing the ribs may cause repetitive mechanical stress to a specific area of the titanium case, potentially leading to a component failure and device malfunction.PrecautionsFor information on precautions, refer to the following sections of the product labeling: clinical considerations; sterilization, storage and handling; implantation and device programming; follow-up testing; explant and disposal; environmental and medical therapy hazards; home and occupational environments. Advise patients to avoid sources of electromagnetic interference (EMI) because EMI may cause the pulse generator to deliver inappropriate therapy or inhibit appropriate therapy.Potential Adverse EventsPotential adverse events from implantation of the ICD system include, but are not limited to, the following: allergic/physical/physiologic reaction, death, erosion/migration, fibrillation or other arrhythmias, lead or accessory breakage (fracture/insulation/lead tip), hematoma/seroma, inappropriate or inability to provide therapy (shocks/pacing/sensing), infection, procedure related, psychologic intolerance to an ICD system - patients susceptible to frequent shocks despite antiarrhythmic medical management/imagined shocking, and component failure. In rare cases severe complications or device failures can occur.Refer to the product labeling for specific indications, contraindications, warnings/ precautions and adverse events. Rx only.(Rev. M)10