A handbook for clinical practice - part 10 pps

Silvia: “chap17” — 2005/10/6 — 22:32 — page 261 — #13 External automated defibrillators 261 15. Ross P, Nolan J, Hill E, Dawson J, Whimster F, Skinner D. The use of AEDs by police officers in the City of London. Resuscitation 2001; 50: 141–146. 16. van Alem AP, Vrenken RH, de Vos R, Tijssen JG, Koster RW. Use of automated external defibrillator by first responders in out of hospital cardiac arrest: prospective controlled trial. Br Med J 2003; 327: 1312. 17. Capucci A, Aschieri D, Piepoli MF, Bardy GH, Iconomu E, Arvedi M. Tripling survival from sudden cardiac arrest via early defibrillation without traditional education in cardiopulmonary resuscitation. Criculation 2002; 106: 1065–1070. 18. Cummins RO, Chapman PJ, Chamberlain DA, Schubach JA, Litwin PE. In-flight deaths during commercial air travel. How big is the problem? J Am Med Assoc 1988; 259: 1983–1988. 19. Crewdson J. Code blue: survival in the sky. Chicago Tribune. Special Report 1996, June 30. 20. Final rule, April 12, 2001. Washington, DC: Federal Aviation Administration, 2001. Accessed November 22, 2004, at http://dmses.dot.gov/docimages/pdf62/ 126161_web.pdf 21. O’Rourke MS, Donaldson E, Geddes JS. An airline cardiac arrest program. Circulation 1997; 96: 2849–2853. 22. Page RL, Joglar JA, Kowal RC et al. Use of automated external defibrillators by a U.S. airline. N Engl J Med 2000; 343: 1210–1216. 23. Goodwin A. In-flight medical emergencies: an overview. Brit Med J 2000; 321: 1338–1341. 24. Alves PM, de Freitas EJ, Mathias HA et al. Use of automated external defibrillators in a Brazilian airline. A 1-year experience. Arq Bras Cardiol 2001; 76: 310–314. 25. Szmajer M, Rodriguez P, Sauval P, Charetteur M-P, Derossi A, Carli P. Medical assistance during commercial airline flights: analysis of 11 years experience of the Paris emergency medical service (SAMU) between 1989 and 1999. Resuscitation 2001; 50: 147–151. 26. Aviation Medical Assistance Act of 1998, Pub. L. No. 105–170, H.R. 2843, 105th Cong. (1998). Accessed November 22, 2004, at http://dmses.dot.gov/docimages/ pdf48/84064_web.pdf 27. Emergency Telemedicine Centre. http://www.medaire.com/comm_air.html. Accessed June 18, 2004. 28. Valenzuela TD, Roe DJ, Nichol G, Clark LL, Spaite DW, Hardman RG. Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos. N Engl J Med 2000; 343: 1206–1209. 29. Fedoruk JC, Paterson D, Hlynka M, Fung KY, Gobet M, Currie W. Rapid on- site defibrillation versus community program. Prehospital Disaster Med 2002; 17: 102–106. 30. Caffrey SL, Willoughby PA, Pepe PE, Becker LB. Public use of automated external defibrillators. New Engl J Med 2002; 347: 1242–1247. 31. Davies CS, Colquhoun M, Boyle R, Chamberlain D. A national programme for on-site defibrillation by lay persons in selected high-risk areas: initial results. Heart (under review). 32. Wassertheil J, Keane G, Fisher N, Leditschke JF. Cardiac outcomes at the Melbourne Cricket Ground and Shrine of Remembrance using a tiered response strategy–aforerunner to public access defibrillation. Resuscitation 2000; 44: 97–104. 33. The Public Access Defibrillation Trial Investigators. Public access defibrillation trial. N Engl J Med 2004; 351: 1–10. Silvia: “chap17” — 2005/10/6 — 22:32 — page 262 — #14 262 Chapter 17 34. Becker L, Eisenberg M, Fahrenbruch C, Cobb L. Public locations of cardiac arrest: implications for public access defibrillation. Circulation 1998; 97: 2106–2109. 35. Pell JP, Sirel JM, Marsden AK, Ford I, Walker NL, Cobbe SM. Potential impact of public access out of hospital cardiopulmonary arrest: retrospective cohort study. Br Med J 2002; 325: 515. 36. Samson R, Berg R, Bingham R. Use of automated external defibrillators for children: an advisory statement from the Pediatric Advanced Life Support Task Force, International Liaison Committee on Resuscitation. Resuscitation 2003; 57: 237–243. 37. Stiell IG, Wells GA, Field BJ III et al. Improved out-of-hospital cardiac arrest survival through the inexpensive optimization of an existing defibrillation program. OPALS study phase II. Ontario Prehospital Advanced Life Support. J Am Med Assoc 1999; 281: 1175–1181. 38. Forrer CS, Swor RA, Jackson RE, Pascual RG, Scott C, McEachin C. Estimated cost effectiveness of a police automated external defibrillator program in a suburban community: 7 years experience. Resuscitation 2002; 52: 23–29. 39. Groeneveld PW, Kwong JL, Liu Y et al. Cost-effectiveness of automated external defibrillators on airlines. J Am Med Assoc 2001; 286:1482–1489. 40. Nichol G, Hallstrom AP, Ornato JP et al. Potental cost-effectiveness of public access defibrillation in the United States. Circulation 1998; 97: 1315–1320. 41. Nichol G, Valenzuela T, Roe D, Clark L, Huszti E, Wells GA. Cost effectiveness of defibrillation by targeted responders in public settings. Circulation 2003; 108: 697–703. 42. Paradis NA, Martin GB, Rivers EP, et al. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. J Am Med Assoc 1990; 263: 1106–1113. 43. Steen S, Liao Q, Pierre L, Paskevicius A, Sjöberg T. The critical importance of minimal delay between chest compressions and subsequent defibrillation: a haemodynamic explanation. Resuscitation 2003; 58: 249–258. 44. Eftestøl T, Sunde K, Aase SO, Husøy JH, Steen PA. Predicting outcome of defibril- lation by spectral characterization and nonparametric classification of ventricular fibrillation in patients with out-of-hospital cardiac arrest. Circulation 2000; 102: 1523–1529. Silvia: “chap18” — 2005/10/6 — 22:33 — page 263 — #1 CHAPTER 18 Cost-effectiveness of implantable cardioverter-defibrillators Giuseppe Boriani and Greg Larsen Introduction: relevance of the cost-effectiveness issue The field of cardiology occupies a special place in the highly topical healthcare cost-containment issue. In a major survey on healthcare costs in the United States, heart disease turned out to be the most costly medical condition, with 57 506 million US dollars being spent in 1997, for providing health care to affected patients, with a mean expense of 3379 US dollars for each patient requiring treatment [1]. Clearly, one of the most relevant problems of current cardiologic practice must be appropriate deployment (in patients appropriately selected according to consensus guidelines) of a series of treat- ments whose proven efficacy is accompanied by relatively high costs [2]. Such options include implantable cardioverter-defibrillator (ICDs), devices for cardiac resynchronization therapy, drug-eluting stents and devices for left ventricular assistance. In the particular setting of sudden-death prevention, the high costs of ICDs represent a major financial hurdle. Advantages of an economics-based approach Despite the mounting costs that healthcare systems have had to face in recent years, the balancing of benefits against costs has yet to become a primary criterion for deciding whether a medical treatment should be covered by pub- lic services. Instead, both policymakers and healthcare providers have largely focused on cost projections, with a consequent tendency to limit or even reject costly new treatments, despite proven clinical efficacy. In other words, consid- eration of the effects of adopting a new treatment has mainly been based on strictly financial concerns rather than on in-depth economic analysis [3]. Even today, in the United States the Food and Drug Administration and Medicare do not take advantage of cost-effectiveness analysis as a valuable tool for decid- ing resource allocation [4]. The same applies for the vast majority of public decision-makers in Europe. 263 Silvia: “chap18” — 2005/10/6 — 22:33 — page 264 — #2 264 Chapter 18 Cost-effectiveness and cost–benefit analysis have been proposed in various fields of medicine to determine which alternative treatment is most likely to provide maximum health benefits for a given level of financial resources, or which treatment provides a given level of health benefits at the lowest cost. Cost-effectiveness estimates express clinical outcome in terms of “years of added life” or “quality-adjusted life years gained”; on the other hand, cost–benefit analysis directly assigns a monetary value to therapeutic benefits [3–7]. Both these analytical approaches are designed to weigh up the benefits and costs of given medical treatments in order to provide a formal basis for implementation decisions. Cost-effectiveness ratios Cost-effectiveness analysis is designed to evaluate the cost of any thera- peutic intervention with respect to its predictable outcome benefits [3,5,6,8]. The cost of a therapy includes both the direct costs (initial cost of therapy, costs to maintain therapy, and costs caused by any adverse effects) and the indirect costs paid by patients, their families, and/or the community. Effect- iveness is measured as the mean extra number of years survived as a result of a treatment. Incremental cost-effectiveness analysis involves comparison of alternative therapeutic strategies. The cost-effectiveness ratio is commonly expressed as dollars per year of life saved ($/YLS). In the literature [8], a treat- ment is considered very attractive if the cost-effectiveness ratio ranges between 0 and 20 000 $/YLS; attractive between 20 000 and 40 000 $/YLS; border- line between 40 000 and 60 000 $/YLS; unfavorable between 60 000 and 100 000 $/YLS; and absolutely unfavorable above 100 000 $/YLS. Cost-effectiveness ratios of various cardiovascular and noncardiovascular treatments are listed in Table 18.1. It is evident that cost-effectiveness ratios can vary considerably depending on the type of population in treatment. Iden- tification of high-risk patients (“patient targeting”) [8] seems to be the single most important issue in order to reach a favorable cost-effectiveness ratio. An important general observation regards some prolonged treatments without particularly high up-front costs; in the absence of major long-term benefits in terms of survival the ultimate cost-effectiveness ratios of such strategies may turn out to be surprisingly unfavorable. Examples include lipid lowering treatments in patients at relatively low risk, as well as antihypertens- ives and antithrombotic treatment with clopidogrel [8–12]. The ICD: a treatment with a high up-front cost but proven efficacy The ICD has traditionally been seen as an expensive form of treatment, with high up-front costs due to the device itself and the implant (followed over time by maintenance costs for device replacement). Since the ICD first appeared in Silvia: “chap18” — 2005/10/6 — 22:33 — page 265 — #3 Cost-effectiveness of ICD 265 Table 18.1 Cost-effectiveness of various treatments. Treatment Strategy Substrate Patient Characteristics $/YLS or $/QALY Gained Very favorable cost-effectiveness (<20 000 $/YLS) Pacemaker Complete AV block 1400 Beta-blockers Post-MI High risk 3600 Anticoagulant drugs Mitral stenosis AF, f, age 35 4200 Lovastatin Hyperlipidemia Sec prev, chol ≥250 mg/dl, f, age 45–54 4700 Simvastatin Hypercholesterolemia in CAD Age 59, cholesterol 309 mg/dl 1200 (m) 3200 (f) Simvastatin Hypercholesterolemia in CAD Age 59, cholesterol 213 mg/dl 2100 (m) 8600 (f) Simvastatin Hypercholesterolemia in CAD Age 70, cholesterol 309 mg/dl 3800 (m) 6200 (f) Simvastatin Hypercholesterolemia in CAD Age 70, cholesterol 213 mg/dl 6 200 (m) 13 300 (f) PTCA Ischemic heart disease Severe angina, age 55, m, normal EF, 1-vessel disease 8700 CABG Ischemic heart disease Severe angina, main left main coronary stenosis 9200 Aspirin Ischemic heart disease Sec prev 11 000 PTCA Ischemic heart disease Severe angina , age 55, m, low EF, 1-vessel disease 11 600 Captopril Post-MI LVEF ≤0.40, age 60 10 200 Enalapril Heart failure 10 300 Endocardial ICD without EPS VT/ VF LVEF ≥0.25 14 200 CABG Ischemic heart disease Nonsevere angina, 3-vessel disease 18 500 (Continued) Silvia: “chap18” — 2005/10/6 — 22:33 — page 266 — #4 266 Chapter 18 Table 18.1 (Continued). Treatment Strategy Substrate Patient Characteristics $/YLS or $/QALY Gained Favorable cost-effectiveness (20–40 000 $/YLS) Beta-blockers Post-MI Low risk 20 200 Anti-hypertensive therapy Hypertension Diastolic AP ≥ 105 mm Hg 20 600 Lovastatin Hyperlipidemia Sec prev, chol < 250 mg/dl, m, age 55–64 20 200 Catheter ablation VT in structural heart disease patients with ICD Patients with frequent VT episodes 20 923 Endocardial ICD with EPS VT/ VF 25 700 Streptokinase Acute myocardial infarction Age ≥75 27 700 Screening with exercise testing after myocardial infarction a Ischemic heart disease Previous uncomplicated myocardial infarction 21 700–36 166 Primary stent in PTCA Ischemic heart disease Angina, age 55, m, 1-vessel disease 26 800 Endocardial ICD with EPS Ischemic heart disease Low EF, nSVT, high risk 27 000 Clopidogrel Ischemic heart disease Sec prev in patients ineligible to aspirin 31000 Endocardial ICD Heart failure NYHA class II–III, LVEF ≤ 35% 33 192 Borderline cost-effectiveness (40–60 000 $/YLS) Anti-hypertensive therapy Hypertension Diastolic AP 95–104 mm Hg 41 900 CABG Ischemic heart disease Severe angina, 2-vessel disease 42500 Cardiac transplant Severe heart failure 44 300 Lovastatin Hyperlipidemia Sec prev, chol < 250 mg/dl, f, age 55–64 48 600 Ambulatory peritoneal dialysis 57 300 Radio frequency ablation WPW Without symptoms, age 40 57 100 Hospital hemodialysis 59 500 Silvia: “chap18” — 2005/10/6 — 22:33 — page 267 — #5 Cost-effectiveness of ICD 267 Unfavorable cost-effectiveness (60–100 000 $/YLS) CABG Ischemic heart disease Nonsevere angina, 2-vessel disease 72900 Lovastatin Hyperlipidemia Prim prev, chol ≥300 mg/dl, no risk factors (RF), m, age 55–64 78 300 Coronary care unit admission Suspected acute MI Patients with 20% probability of acute myocardial infarction 78 000 Heart transplantation Terminal heart disease Patients aged 55 or younger 100 000 Very unfavorable cost-effectiveness (>100 000 $/YLS) PTCA Ischemic heart disease Nonsevere angina, age 55, normal LVEF, 1-vessel disease (left anterior descending) 109 000 Clopidogrel Ischemic heart disease Sec prev with clopidogrel alone in all patients or in combination with aspirin 130 000 Neurosurgery Malignant intracranial tumor 325 000 Coronary care unit admission Suspected acute MI Patients with 5% probability of acute myocardial infarction 328 500 CABG Ischemic heart disease Nonsevere angina, 1-vessel disease 1 142 000 Lovastatin Hyperlipidemia Prim prev, chol≥300 mg/dl, no risk factors (RF), f, age 45–54 2 024 800 Notes: AF = atrial fibrillation; AP = arterial pressure; CAD = coronary artery disease; CABG = coronary artery by-pass graft; Chol = cholesterolemia; EPS = electrophysiological study; f = female; ICD = implantable cardioverter-defibrillator; LVEF = left ventricu- lar ejection fraction; m = male; MI = myocardial infarction; nSVT = nonsustained ventricular tachycardia; Prim prev = primary prevention; Proph = prophylaxis; PTCA = percutaneous transluminal coronary angioplasty; RF = coronary risk factors; Sec prev = secondary prevention; VF = ventricular fibrillation; VT = ventricular tachycardia; WPW = Wolff–Parkinson–White syndrome; $/YLS = dollars per year of saved life; $/QALY = dollars per quality-adjusted year of life gained. Source: Modified from: Kupersmith [8], Tengs et al. [9], Johannesson et al. [10], Boriani et al. [11], and Gaspoz et al. [12]. a Assuming discounted life expectancy of 6–10 years with coronary revascularization. Silvia: “chap18” — 2005/10/6 — 22:33 — page 268 — #6 268 Chapter 18 clinical practice, the indications for use of ICDs have broadened dramatically from a few selected patients with previous cardiac arrest to a large cohort of patients with heterogeneous underlying heart diseases, identified as subjects at high risk of sudden death [13–16]. Transvenous implantation has markedly decreased the hospitalization costs and contributed to widespread use of ICD systems [13,17,18]. Despite marked price reductions in the last decade, the cost issue continues to limit full acceptance and application of ICD therapy, especially as regards increased use for primary prevention of sudden death [11,19–22]. The clinical efficacy of ICDs has been clearly demonstrated in specific subsets of patients. Table 18.2 summarizes the results of main randomized controlled trials [23–31] – regarding both primary and secondary prevention of sudden cardiac death – in terms of ability to improve overall survival. It is noteworthy that ICD efficacy was generally associated with favorable values for “number needed to treat” to save a life, much lower than those reported for a series of widely used pharmacological treatments (Figure 18.1). Analysis of the res- ults of randomized controlled trials involving over 6000 patients [7] have prompted definition of consensus guidelines for ICD use [14–16]. Indications for devices with cardioversion-defibrillation capabilities are also expected to increase in view of the increasing evidence emerging from the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) study [30] that cardiac resynchronization therapy in patients with severe heart failure may improve overall survival, in addition to providing favorable effects in terms of quality of life, exercise capacity, and reductions in hospitalization due to heart failure [32–37]. Implementation of ICD use in clinical practice Even when the information derived from randomized controlled trials has been incorporated into consensus guidelines, barriers to widespread imple- mentation still exist [38]. Although it is difficult to assess the degree of compliance to consensus guidelines in daily practice, indirect evidence sug- gests that even in the United States the actual rate of ICD implantation is lower than projections based on the current guidelines [39]. Such a gap could be of major relevance for public health, considering the evidence of ICDs’ efficacy in primary prevention of sudden death in patients with severe left ventricular dysfunction/heart failure provided by the Multicenter Automatic Defibrillat- tor Implantation Trial (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials [21,22,29,31]. Marked discrepancies clearly exist in the implementation of clinical indica- tions to ICD implantation based on randomized studies (MADIT II, SCD-HeFT) testing the impact of device therapy on primary prevention of sudden death. For instance, there are still major differences between the implant rates in the United States and Europe [2]. This heterogeneity reflects variations between different countries regarding general economic status, type of Silvia: “chap18” — 2005/10/6 — 22:33 — page 269 — #7 Cost-effectiveness of ICD 269 Table 18.2 Main prospective controlled trials on treatment with ICD versus control in primary and secondary prevention of sudden death. Number of Patients Mean Age (Years) Women (%) NYHA Class >II(%) Mean LVEF (%) Follow-up (Months) Annual Control Group Mortality (%) Relative Risk Reduction in Total Mortality with ICD (%) p-value in the Comparison of ICD Versus Control for Overall Survival Secondary prevention trials AVID (1997) 1016 65 21 9 32 18 ± 12 12 31 <.02 CIDS (2000) 659 64 15 11 34 36 10 20 .142 CASH (2000) 288 58 20 17 45 57 ± 34 9 23 .081 Metaanalysis (2000) 1866 63 18 11 34 28 — 28 .0006 Primary prevention trials MADIT (1996) 196 63 8 — 26 27 17 54 .009 MUSTT (1999) 704 67 10 24 30 39 14 51 <.001 MADIT II (2002) 1232 65 15 29 23 20 10 31 .016 COMPANION (2004) 1634 66 23 86 22 16 19 43 .002 SCD-HeFT (2004) 2521 60 23 30 25 45.5 7.2 23 .007 Notes: ICD = implantable cardioverter-defibrillator; LVEF = left ventricular ejection fraction. Silvia: “chap18” — 2005/10/6 — 22:33 — page 270 — #8 270 Chapter 18 60 50 40 30 20 10 Years of tested treatment 0 3 4 11 4 12 14 25 14 20 25 29 29 37 57Drugs ICD Number of patients needed to treat to save one life MUSTT MADIT MADIT II COMPANION-CRTD SCD-HeFT AVID COMPANION-CRT COPERNICUS SAVE CIBIS II MERIT HF CAPRICORN Amiodarone HOPE 5 2.4 3 3 5 1 1 0.8 3.5 1.5 2 411 Figure 18.1 Number needed to treat (NNT) to save one life in a series of studies related to ICD treatment or various pharmacological treatments. CRT = cardiac resynchronization therapy; CRTD = cardiac resynchronization therapy + defibrillation capabilities. healthcare system, and arrangements for reimbursement of device costs [2,40]. Moreover, a decision not to implant an ICD in a patient with a MADIT II or SCD-HeFT indication can entail very different potential medicolegal implic- ations in different countries [41]. Such considerations may help explain why ICD implant rates can vary considerably even among European countries sharing broadly similar economic status. Available ICD cost-effectiveness estimates Table 18.3 provides an overview of cost-effectiveness estimates of ICD treat- ment generated by observational data, projections based on decision models (retrospective analysis), and – more recently – randomized trials [11,42–50]. Use of ICDs in selected patients (or subgroups of patients) at high risk of sudden death has often generated cost-effectiveness estimates that are com- parable with or lower than other accepted treatments, including renal dialysis, which costs about 50 000–60 000 $/YLS [8,9,11,21]. Nevertheless, a broad range of cost-effectiveness ratios have emerged, ranging from economically attractive to very expensive values. In general, the recent randomized trials have provided less attractive ratios than those derived from the initial mod- eling studies [51]. A further source of variability is the time horizon within which cost-effectiveness is estimated. When Hlatky and Bigger [52] projected the results of all the trials published until 2001, to gauge the full gain in life expectancy, they obtained a cost-effectiveness ratio of 31 500 $/YLS, in line with what is currently considered fully acceptable in developed countries. [...]... Epstein AE et al ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (ACC/AHA/NASPE committee to update the 1998 pacemaker guidelines) J Am Coll Cardiol 2002; 40: 1703–1719 15 Priori SG, Aliot E, Blomstrom-Lundqvist C et al Task force on sudden cardiac... Study Hamburg (CASH) Circulation 2000; 102 : 748–754 25 Connolly SJ, Gent M, Roberts RS et al Canadian implantable defibrillator study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone Circulation 2000; 101 : 1297–1302 26 Connolly SJ, Hallstrom AP, Cappato R et al Meta-analysis of the implantable cardioverter-defibrillator secondary prevention trials AVID, CASH and... postinfarction risk stratification, 50 related incidence of SCD, 7, 22 airlines, automated external defibrillators, 253–4 airports, automated external defibrillators, 254–5 aldosterone antagonists, 97, 117, 168–9, 208 alpha-galactosidase replacement therapy, 210 ambulatory ECG monitoring, 51–3 American College of Cardiology (ACC)/American Heart Association (AHA) ICD guidelines, 115 preparticipation screening... Implantable Defibrillator (AVID) Investigators A comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias N Engl J Med 1997; 337: 1576–1583 24 Kuck KH, Cappato R, Siebels J et al Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest... CIDS studies Antiarrhythmics Versus Implantable Defibrillator study Cardiac Arrest Study Hamburg Canadian Implantable Defibrillator Study Eur Heart J 2000; 21: 2071–2078 27 Moss AJ, Hall J, Cannom DS et al Improved survival with an implantable defibrillator in patients with coronary disease at high risk for ventricular arrhythmia Multicenter Automatic Defibrillator Implantation Trial Investigators N Engl... for participation, 198–9 preparticipation screening, 197–8 see also exercise athlete’s heart, 192 athletic performance-enhancing substances, 196–7 ATRAMI study, 55, 66–7 atrial fibrillation (AF), 139 in cardiac channelopathies, 140 in dilated cardiomyopathy, 118 familial (FAF), 135, 139–40 in hypertrophic cardiomyopathy, 111, 114 mechanisms, 35 in mitral regurgitation, 154–6, 157 atrioventricular (AV)... calcium-after-transients, in heart failure, 41 calcium channel, cardiac L-type, 133–6 calsequestrin, 135, 141–2 CAMIAT, 100 , 207 cardiac arrest automated external defibrillators see automated external defibrillators 283 definitions, 3–4 previous, 111, 119 cardiac resynchronization therapy (CRT), 171–2, 223–4, 268 cost effectiveness, 275 in dilated cardiomyopathy, 118 see also pacemakers cardiac transplantation candidates,... patients antiarrhythmic drugs, 99, 100 autonomically based antiarrhythmic therapy, 68–70 autonomic nerve growth and degeneration, 65–6 autonomic reflexes, 63–4 catheter ablation therapy, 242–3 Home AED Trial (HAT), 256–7 ICD therapy trials, 56, 101 –5 myocardial revascularization, 98–9 nonantiarrhythmic drug therapy, 97 risk stratification, 48–9, 50–7 ambulatory ECG monitoring, 51–3 Bayesian approach, 49–50 clinical. .. pacing in patients with heart failure and intraventricular conduction delay N Engl J Med 2001; 344: 873–880 33 Abraham WT, Fisher WG, Smith AL et al Cardiac resynchronization in chronic heart failure N Engl J Med 2002; 346: 1845–1853 34 Bradley DJ, Bradley EA, Baughman KL et al Cardiac resynchronization and death from progressive heart failure A meta-analysis of randomized controlled trials JAMA 2003;... McAlister FA, Ezekowitz JA, Wiebe N et al Systematic review: cardiac resynchronization in patients with symptomatic heart failure Ann Intern Med 2004; 141: 381–390 36 Boriani G, Biffi M, Martignani C et al Cardiac resynchronization by pacing: an electrical treatment of heart failure Int J Cardiol 2004; 94: 151–161 37 Auricchio A, Abraham WT Cardiac resynchronization therapy: current state of the art: . arrhythmias? Circulation 2000; 102 : IV52–IV57. 14. Gregoratos G, Abrams J, Epstein AE et al. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: a report. economic analysis [3]. Even today, in the United States the Food and Drug Administration and Medicare do not take advantage of cost-effectiveness analysis as a valuable tool for decid- ing resource allocation. assessment of value in cardio- vascular medicine: part I. Circulation 2002; 106 : 516–520. 6. Mark DB, Hlatky MA. Medical economics and the assessment of value in cardi- ovascular medicine: part