***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: More than 1 million Americans per year have acute myocardial infa rct ion ( 1 ) . Those who survive to hospital discharge have a 5 % to 10 % risk for dying suddenly within the first year ( 27 ) . Prevention of those sudden deaths is an important goal , and several approaches have been used to accomplish it . Secondary prevention with type I antiarrhythmic drugs has been unsuccessful ( 8) . Prophylactic use of amiodarone has significantly reduced death after myocardial infa rct ion in some but not all r and omized trials . Quantitative overviews of these studies suggest that amiodarone reduces mortality rates by 10 % to 20 % ( 9 , 10 ) . Recent studies of the implantable cardioverter defibrillator ( ICD ) in patients who have no history of sustained arrhythmia have also had mixed results , with positive results in patients with unsustained ventricular tachycardia ( 11 , 12 ) and negative results in patients with reduced ejection fraction and positive results on signal-averaged electrocardiography ( 13 ) . The use of prophylactic ICD has nevertheless attracted great interest because of the demonstrated efficacy of the device in patients who have had a documented episode of ventricular fibrillation or sustained ventricular tachycardia ( 1416 ) . Although ongoing or planned r and omized , controlled trials ( 17 , 18 ) will clarify the role of ICDs and amiodarone therapy in patients who have had myocardial infa rct ions , the results of these trials will not be available until late 2001 at the earliest . We previously showed that ICDs can be cost-effective in patients who have survived an episode of ventricular fibrillation or sustained ventricular tachycardia ( 19 ) . These findings can not be extrapolated to prophylactic use of ICDs in patients who have had myocardial infa rct ions because the risk for sudden death in such patients is lower . Indeed , the current st and ard of care for patients who have had myocardial infa rct ion does not include prophylactic antiarrhythmic therapy . With recent evidence of the efficacy of antiarrhythmia management in patients who have had myocardial infa rct ions , the potential cost-effectiveness of prophylactic antiarrhythmic therapy should be reassessed . In this study , we estimated survival and costs for patients with past myocardial infa rct ion who were treated with amiodarone , ICD , or no specific antiarrhythmic therapy . We evaluated the level of efficacy needed to make  prophylactic therapy  with an ICD or amiodarone  cost-effective in three groups of patients with past myocardial infa rct ion who were stratified by left ventricular ejection fraction . Methods We used a decision model to estimate the length of life and expenditures for patients who had myocardial infa rct ion without symptomatic , sustained ventricular arrhythmia and who received one of three treatment strategies : ICD , amiodarone therapy , or no antiarrhythmic therapy ( Figure 1 ) . We stratified patients into three groups according to ejection fraction : less than or equal to 0.3 , 0.31 to 0.4 , and greater than 0.4 . Although the ability of many clinical factors to predict the risk for sudden cardiac death has been analyzed and several independent risk factors have been identified ( 20 ) , ejection fraction has consistently been the single most powerful predictor of sudden cardiac death ( 2124 ) . Figure 1 . The decision model . The square node on the left represents a choice among three alternative treatments : implantable cardiac defibrillator ( ICD ) , amiodarone , and no antiarrhythmic treatment . Circles represent chance nodes . Patients who receive an ICD are at risk for death from the implant procedure . Patients who do not die of ICD implantation and patients who are receiving amiodarone or no treatment enter the Markov tree ( denoted by rectangles containing circles and an arrow ) . The Markov tree represents the clinical events that can occur during each 1-month period as a patient is followed until death . During each 1-month period , a patient may die from arrhythmic or nonarrhythmic cardiac causes and may also die of noncardiac causes . If none of these events occur , the patient remains well for the 1-month period . Patients who have an ICD may have a lead infection or failure that causes them to withdraw from treatment ( and to switch to no antiarrhythmic therapy ) . Patients who receive amiodarone are at risk for amiodarone toxicity . In our analysis , a patient may die of toxicity , withdraw from treatment ( and switch to no antiarrhythmic therapy ) , or have acute toxicity that does not require discontinuation . We adhered to the recommendations of the Panel on Cost-effectiveness in Health and Medicine ( 25 , 26 ) . We used a societal perspective to evaluate health benefits and costs , discounting each at a rate of 3 % per year . We performed one-way sensitivity analyses on all of the model variables , as well as selected two-way , three-way , and n-way ( Monte Carlo ) probabilistic sensitivity analyses ( 27 ) . Decision Model We developed a Markov model ( 28 , 29 ) ( SMLTree decision analysis software , version 2.9 , J. Hollenberg , New York , New York ) by modifying a model used previously to assess the cost-effectiveness of ICDs or amiodarone in patients who had experienced sustained ventricular arrhythmia ( 19 , 30 ) ( Figure 1 ) . Our current model includes the possibility of no antiarrhythmic therapy and uses data relevant to the lower-risk population of patients who have survived myocardial infa rct ion . The model tracks a cohort of patients who received prophylactic ICD ( implanted without a thoracotomy ) , amiodarone therapy , or no antiarrhythmic therapy .  Patients who received an ICD were at risk for procedural death . Patients who survived ICD implantation , patients treated with amiodarone , and patients who received no antiarrhythmic therapy  entered a Markov tree ( Figure 1 ) . Each month , these patients were at risk for sudden cardiac death , nonsudden cardiac death , and noncardiac death . We assumed that 2 % of the ICD-treated patients would have the ICD removed because of infection or lead complications during the first year and that 1 % of surviving patients would withdraw from ICD therapy in each subsequent year ( 3133 ) . Similarly , we assumed that 10 % of the amiodarone-treated patients would withdraw from therapy because of toxicity during the first year and that 5 % of surviving patients would withdraw in each subsequent year ( 3445 ) . Because the use of antiarrhythmic therapy in the postmyocardial infa rct ion population would be prophylactic , we assumed that crossovers between the ICD and amiodarone strategies would be less likely . Therefore , patients who withdrew from one antiarrhythmic treatment would be withdrawn from prophylactic treatment . Patient Sample Our base-case analyses evaluated the cost-effectiveness of each antiarrhythmic management strategy in three cohorts of patients defined by ejection fraction ( Table 1 ) . We obtained mortality and inpatient cost data for patients from the Myocardial Infa rct ion Triage and Intervention ( MITI ) patient registry ( 46 ) who had had myocardial infa rct ion . Between 1988 and 1994 , approximately 40 000 patients were admitted to cardiac care units in 19 hospitals in Seattle , Washington . Hospitals participating in the registry include 2 university hospitals , 2 staff-model health maintenance organization hospitals , 1 Veterans Affairs hospital , and 14 community hospitals . During most of the study period , 10 of the participating hospitals had on-site catheterization laboratories and 5 performed bypass surgery . During the study period , 12 000 patients presented with an  acute myocardial infa rct ion ; of these , ejection fraction was measured in approximately 3000 . Table 1 . Clinical Characteristics of the Myocardial Infa rct ion Triage and Intervention Patient Sample Patients with ejection fractions of 0.3 or less had a mean age ( SD ) of 66.5 11.92 years ( range , 26 to 95 years ) , 24.6 % 43.1 % had a history of congestive heart failure , 62.8 % 48.4 % received an initial catheterization  , and 26.6 % 44.3 % underwent  initial revascularization . Patients with ejection fractions between 0.31 and 0.4 had a mean age of 63.5 12.22 years ( range , 36 to 97 years ) , 11.0 % 31.3 % had a history of congestive heart failure , 73.2 % 44.3 % underwent catheterization , and 37.6 % 48.4 % had revascularization . Finally , patients with ejection fractions greater than 0.4 had a mean age of 61.5 11.83 years ( range , 26 to 92 years ) , 3.5 % 18.4 % had a history of congestive heart failure , 88.0 % 32.4 % received an initial catheterization , and 48.0 % 50 % underwent revascularization . We compared the characteristics of patients who had ejection fraction measurements with those of patients in the MITI registry for whom ejection fraction was not measured . The clinical characteristics listed in Table 1 differed significantly between these groups , but the rates of sudden cardiac , nonsudden cardiac , noncardiac , and overall mortality did not differ significantly after we controlled for age , sex , and cardiac history ( 24 ) . From the MITI registry , we obtained monthly probabilities of cardiac death for the three ejection fraction cohorts . The MITI project used hospital discharge summaries and death certificates to identify patients who died of cardiac causes during follow-up while in or out of the hospital ( 47 ) . We classified cardiac deaths that occurred in neither a hospital nor a nursing home as sudden and potentially preventable by arrhythmic therapy ; we classified as nonsudden the cardiac deaths that occurred in a hospital or a nursing home . We recognized the limitations of this classification system and therefore analyzed a range of ICD efficacies . Table 1 summarizes the probabilities of sudden and nonsudden cardiac death for the three cohorts over time . To estimate life expectancy after the end of follow-up in the MITI cohort , we extrapolated the annual cardiac mortality rate for subsequent years from that observed during follow-up and assumed that the noncardiac mortality rate would equal that in the general U.S. population ( 48 ) . Effectiveness of Background —The implantable cardioverter-defibrillator ( ICD ) is an effective but expensive device . We used prospect ively collected data from a large r and omized clinical trial of secondary prevention of life-threatening ventricular arrhythmias to determine the cost-effectiveness of the ICD compared with antiarrhythmic drug ( AAD ) therapy , largely with amiodarone . Methods and Results —Charges for initial and repeat hospitalizations , emergency room , and day surgery stays and the costs of antiarrhythmic drugs  were collected on 1008 patients . Detailed records of all other medical encounters and expenses were collected on a subgroup of 237 patients . Regression models were then created to attribute these expenses to the rest of the patients . Charges were converted to 1997 costs using st and ard methods . Costs and life years were discounted at 3 % per year . Three-year survival data from the Antiarrhythmics Versus Implantable Defibrillators trail were used to calculate the base-case cost-effectiveness ( C/E ) ratio . Six-year , twenty-year , and lifetime C/E ratios were also estimated . At 3 years , total costs were $ 71 421 for a patient taking AADs and $ 85 522 for a patient using an ICD , and the ICD provided a 0.21-year survival benefit over AAD treatment . The base-case C/E ratio was thus $ 66 677 per year of life saved by the ICD compared with AAD therapy ( 95 % CI , $ 30 761 to $ 154 768 ) . Six- and 20-year C/E ratios remained stable between $ 68 000 and $ 80 000 per year of life saved . Conclusions —The ICD is moderately cost-effective for secondary prevention of life-threatening ventricular arrhythmias , as judged from prospect ively collected data in a r and omized clinical trial Background —In the Canadian Implantable Defibrillator Study ( CIDS ) , we assessed the cost-effectiveness of the implantable cardioverter-defibrillator ( ICD ) in reducing the risk of death in survivors of previous ventricular tachycardia ( VT ) or fibrillation ( VF ) . Methods and Results —Healthcare re source use was collected prospect ively on the first 430 patients enrolled in CIDS ( n=212 ICD , n=218 amiodarone ) .  Mean cost per patient , adjusted for censoring , was computed for each group based on initial therapy assignment . Incremental cost-effectiveness of ICD therapy was computed as the ratio of the difference in cost ( ICD minus amiodarone ) to the difference in life expectancy ( both discounted at 3 % per year ) . All costs are in 1999 Canadian dollars ( C$ 1 ≈ US$ 0.65 ) . Over 6.3 years , mean cost per patient in the ICD group was C$ 87 715 versus C$ 38 600 in the amiodarone group ( difference C$ 49 115 ; 95 % CI C$ 25 50 
    Output:
    
For secondary prevention , the results showed that the ICD is considered cost-effective in patients with more risk .
For primary prevention , the cost-effectiveness of ICD has been widely studied , but uncertainty about its cost-effectiveness remains .
The cost-effectiveness ratios vary between studies depending on the patient characteristics , methodology , perspective , and national setting s. Among the European studies , the conclusions are varied , where the ICD is considered cost-effective or not dependent on the study