Prophylactic Defibrillator Implantation — Toward an Evidence-Based Approach
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《新英格兰医药杂志》
Most patients who have an out-of-hospital cardiac arrest do not survive. Thus, the use of a prophylactic implantable cardioverter–defibrillator (ICD) for the primary prevention of sudden death is a conceptually attractive option for high-risk patients. Several clinical trials have previously shown that ICDs reduced mortality in patients with coronary artery disease who had not yet had a life-threatening arrhythmia and who were selected on the basis of either the results of electrophysiological testing or left ventricular dysfunction.1,2,3,4 In the past year, four multicenter clinical trials have helped refine the selection of appropriate patients for ICD therapy. In addition to confirming and expanding data on patients with chronic coronary artery disease, these studies added new information about the treatment of patients with nonischemic cardiomyopathy,5 recent myocardial infarction,6 and wide QRS complexes.7
The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),8 reported in this issue of the Journal, included patients with left ventricular dysfunction regardless of cause and used the presence of heart failure despite medical therapy and a left ventricular ejection fraction of less than 36 percent as an entry criterion. The trial convincingly showed that amiodarone does not decrease mortality among patients with left ventricular dysfunction and heart failure. The study also showed that patients who received an ICD have a better outcome than those who were treated with medical therapies, including angiotensin-converting–enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers. The study confirmed the effectiveness of ICDs in prolonging survival among patients with heart failure and coronary disease, although the benefit was smaller than that seen in prior studies, perhaps because of better medical therapy in the control group.2,3
Only one large study had previously examined the ability of the ICD to decrease mortality among patients with nonischemic cardiomyopathy. The Defibrillators in NonIschemic Cardiomyopathy Treatment Evaluation (DEFINITE) study showed a relative 35 percent decrease in overall mortality with the use of ICD therapy, a difference that did not quite reach statistical significance.5 In SCD-HeFT, there was a 27 percent relative decrease in mortality among patients with nonischemic cardiomyopathy. The results of these two studies are broadly consistent and suggest that ICDs can improve survival among patients with nonischemic cardiomyopathy and severe left ventricular dysfunction.
Although the results of SCD-HeFT are generally consistent with previous clinical trials, there are some differences that require further investigation. As noted by the authors, the benefit of the ICD in SCD-HeFT appeared to be more marked in patients with less severe congestive heart failure (New York Heart Association class II) than it did in those with class III heart failure — a finding that differed from those of other trials. Other studies have shown that the benefit of the ICD either did not vary according to heart-failure class or was greater among patients with class III congestive heart failure. The SCD-HeFT investigators believe that this difference may be a statistical aberration. To investigate this hypothesis further, it will be necessary to analyze data on the relative benefits of ICD among patients with ischemic and nonischemic cardiomyopathy who have class II and class III congestive heart failure.
Although the ICD has been shown to be beneficial in patients with chronic left ventricular dysfunction, this is not the case when the ICD is used immediately after myocardial infarction.7 Thus, ICD therapy for the primary prevention of sudden death in patients with left ventricular dysfunction should be considered a long-term rather than a short-term intervention.
The addition of a left ventricular lead to provide resynchronization therapy has been shown to improve heart failure and decrease mortality among patients with left ventricular dysfunction and wide QRS complexes.9 Patients with class III congestive heart failure who meet indications for the prophylactic use of an ICD and have wide QRS complexes should receive resynchronization therapy with an ICD. There are not yet sufficient data to recommend such therapy for patients with class II congestive heart failure and wide QRS complexes or for patients with narrow QRS complexes but with evidence of mechanical dyssynchrony. ICD therapy is not specifically recommended for the primary prevention of sudden death for patients with class IV congestive heart failure, since the competing risk of progressive pump failure may outweigh the survival benefit from rapid termination of ventricular tachyarrhythmias. However, since some patients who receive resynchronization therapy will have improvement in their heart failure, the potential benefits of such therapy in this population should be studied further.
Although ICDs have been shown to be lifesaving, they are expensive. The cost (including follow-up) may reach as much as $40,000, even if single-lead, "low-cost" ICDs are used. The effect of routine prophylactic use of ICDs on health care costs in the United States must be carefully considered.10 A recent preliminary analysis of data from SCD-HeFT suggests that ICDs are indeed cost-effective on the basis of routinely accepted norms.11 The Center for Medicare and Medicaid Services has recently suggested in a preliminary coverage decision that patients with left ventricular dysfunction and an ejection fraction of less than 31 percent should be eligible to receive a single-chamber ICD as long as they are enrolled in a prospective registry, as discussed elsewhere in this issue of the Journal.12 This proposed coverage decision is a reasonable compromise between ensuring that patients at highest risk receive ICD therapy and avoiding a large escalation in health care costs. It is based on post hoc analyses of SCD-HeFT and DEFINITE, in both of which the benefit of ICDs appeared to be less in patients with left ventricular ejection fractions of 31 to 35 percent (Al-Khatib S: personal communication).
Although the addition of an atrial lead to an ICD could theoretically decrease the incidence of inappropriate ICD shocks, there have been no prospective studies showing convincing clinical benefit through the addition of an atrial lead. Thus, until more data are available, implanting single-chamber ICDs in most patients who receive a prophylactic ICD is appropriate. However, allowing atrial leads to be added for arrhythmia discrimination and therapy in patients with documented supraventicular tachyarrhythmias seems reasonable. Additional data regarding outcome from a registry of patients receiving ICDs will be beneficial. However, whether the data in this registry will be sufficiently comprehensive to permit meaningful outcome analyses will take several years to determine.
How should physicians apply the results of the recent ICD trials in clinical practice? Patients with ejection fractions of less than 31 percent should be considered for a single-chamber ICD to improve their survival. Resynchronization therapy should be used when appropriate. Patients with ejection fractions of 31 to 40 percent pose a more difficult treatment challenge. For patients with coronary disease, data from some trials support the use of electrophysiological testing as an additional risk-stratification tool.4 For patients with nonischemic cardiomyopathy, reimbursement guidelines and clinical judgment should be used to evaluate the risk–benefit ratio of the use of ICDs for patients with an ejection fraction of 31 to 35 percent, and the use of ICDs is probably not beneficial for patients with an ejection fraction of more than 35 percent.
Although the ICD is effective in reducing mortality among patients with left ventricular dysfunction, it may also result in morbidity, including a high incidence of inappropriate shocks. Not all patients with left ventricular dysfunction should immediately receive an ICD. However, physicians should evaluate and discuss the risk–benefit ratio for each patient regardless of the cause of heart failure, keeping in mind that evidence now supports the concept that ICDs will prolong life and should be used in most patients with severe left ventricular dysfunction.
Dr. Kadish reports having received research support from Guidant, Medtronic, and St. Jude Medical's Cardiac Rhythm Management Division.
Source Information
From the Division of Cardiology, Department of Medicine, Northwestern University, Feinberg School of Medicine, and the Clinical Trials Unit, Northwestern Cardiovascular Institute — both in Chicago.
References
Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933-1940.
Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882-1890.
Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. N Engl J Med 2000;342:1937-1945.
Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-2158.
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Hlatky MA. Evidence-based use of cardiac procedures and devices. N Engl J Med 2004;350:2126-2128.
Kadish A. SCD-HeFT and DEFINITE substudies: establishing a formative role for ICD therapy in the primary prevention of sudden death. New York: WebMD Medscape Health Network, 2004. (Accessed January 3, 2005, at http://www.medscape.com/viewarticle/496072.)
McClellan MB, Tunis SR. Medicare coverage of ICDs. N Engl J Med 2005;352:222-224.(Alan Kadish, M.D.)
The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),8 reported in this issue of the Journal, included patients with left ventricular dysfunction regardless of cause and used the presence of heart failure despite medical therapy and a left ventricular ejection fraction of less than 36 percent as an entry criterion. The trial convincingly showed that amiodarone does not decrease mortality among patients with left ventricular dysfunction and heart failure. The study also showed that patients who received an ICD have a better outcome than those who were treated with medical therapies, including angiotensin-converting–enzyme inhibitors, angiotensin-receptor blockers, and beta-blockers. The study confirmed the effectiveness of ICDs in prolonging survival among patients with heart failure and coronary disease, although the benefit was smaller than that seen in prior studies, perhaps because of better medical therapy in the control group.2,3
Only one large study had previously examined the ability of the ICD to decrease mortality among patients with nonischemic cardiomyopathy. The Defibrillators in NonIschemic Cardiomyopathy Treatment Evaluation (DEFINITE) study showed a relative 35 percent decrease in overall mortality with the use of ICD therapy, a difference that did not quite reach statistical significance.5 In SCD-HeFT, there was a 27 percent relative decrease in mortality among patients with nonischemic cardiomyopathy. The results of these two studies are broadly consistent and suggest that ICDs can improve survival among patients with nonischemic cardiomyopathy and severe left ventricular dysfunction.
Although the results of SCD-HeFT are generally consistent with previous clinical trials, there are some differences that require further investigation. As noted by the authors, the benefit of the ICD in SCD-HeFT appeared to be more marked in patients with less severe congestive heart failure (New York Heart Association class II) than it did in those with class III heart failure — a finding that differed from those of other trials. Other studies have shown that the benefit of the ICD either did not vary according to heart-failure class or was greater among patients with class III congestive heart failure. The SCD-HeFT investigators believe that this difference may be a statistical aberration. To investigate this hypothesis further, it will be necessary to analyze data on the relative benefits of ICD among patients with ischemic and nonischemic cardiomyopathy who have class II and class III congestive heart failure.
Although the ICD has been shown to be beneficial in patients with chronic left ventricular dysfunction, this is not the case when the ICD is used immediately after myocardial infarction.7 Thus, ICD therapy for the primary prevention of sudden death in patients with left ventricular dysfunction should be considered a long-term rather than a short-term intervention.
The addition of a left ventricular lead to provide resynchronization therapy has been shown to improve heart failure and decrease mortality among patients with left ventricular dysfunction and wide QRS complexes.9 Patients with class III congestive heart failure who meet indications for the prophylactic use of an ICD and have wide QRS complexes should receive resynchronization therapy with an ICD. There are not yet sufficient data to recommend such therapy for patients with class II congestive heart failure and wide QRS complexes or for patients with narrow QRS complexes but with evidence of mechanical dyssynchrony. ICD therapy is not specifically recommended for the primary prevention of sudden death for patients with class IV congestive heart failure, since the competing risk of progressive pump failure may outweigh the survival benefit from rapid termination of ventricular tachyarrhythmias. However, since some patients who receive resynchronization therapy will have improvement in their heart failure, the potential benefits of such therapy in this population should be studied further.
Although ICDs have been shown to be lifesaving, they are expensive. The cost (including follow-up) may reach as much as $40,000, even if single-lead, "low-cost" ICDs are used. The effect of routine prophylactic use of ICDs on health care costs in the United States must be carefully considered.10 A recent preliminary analysis of data from SCD-HeFT suggests that ICDs are indeed cost-effective on the basis of routinely accepted norms.11 The Center for Medicare and Medicaid Services has recently suggested in a preliminary coverage decision that patients with left ventricular dysfunction and an ejection fraction of less than 31 percent should be eligible to receive a single-chamber ICD as long as they are enrolled in a prospective registry, as discussed elsewhere in this issue of the Journal.12 This proposed coverage decision is a reasonable compromise between ensuring that patients at highest risk receive ICD therapy and avoiding a large escalation in health care costs. It is based on post hoc analyses of SCD-HeFT and DEFINITE, in both of which the benefit of ICDs appeared to be less in patients with left ventricular ejection fractions of 31 to 35 percent (Al-Khatib S: personal communication).
Although the addition of an atrial lead to an ICD could theoretically decrease the incidence of inappropriate ICD shocks, there have been no prospective studies showing convincing clinical benefit through the addition of an atrial lead. Thus, until more data are available, implanting single-chamber ICDs in most patients who receive a prophylactic ICD is appropriate. However, allowing atrial leads to be added for arrhythmia discrimination and therapy in patients with documented supraventicular tachyarrhythmias seems reasonable. Additional data regarding outcome from a registry of patients receiving ICDs will be beneficial. However, whether the data in this registry will be sufficiently comprehensive to permit meaningful outcome analyses will take several years to determine.
How should physicians apply the results of the recent ICD trials in clinical practice? Patients with ejection fractions of less than 31 percent should be considered for a single-chamber ICD to improve their survival. Resynchronization therapy should be used when appropriate. Patients with ejection fractions of 31 to 40 percent pose a more difficult treatment challenge. For patients with coronary disease, data from some trials support the use of electrophysiological testing as an additional risk-stratification tool.4 For patients with nonischemic cardiomyopathy, reimbursement guidelines and clinical judgment should be used to evaluate the risk–benefit ratio of the use of ICDs for patients with an ejection fraction of 31 to 35 percent, and the use of ICDs is probably not beneficial for patients with an ejection fraction of more than 35 percent.
Although the ICD is effective in reducing mortality among patients with left ventricular dysfunction, it may also result in morbidity, including a high incidence of inappropriate shocks. Not all patients with left ventricular dysfunction should immediately receive an ICD. However, physicians should evaluate and discuss the risk–benefit ratio for each patient regardless of the cause of heart failure, keeping in mind that evidence now supports the concept that ICDs will prolong life and should be used in most patients with severe left ventricular dysfunction.
Dr. Kadish reports having received research support from Guidant, Medtronic, and St. Jude Medical's Cardiac Rhythm Management Division.
Source Information
From the Division of Cardiology, Department of Medicine, Northwestern University, Feinberg School of Medicine, and the Clinical Trials Unit, Northwestern Cardiovascular Institute — both in Chicago.
References
Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933-1940.
Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-883.
Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med 1999;341:1882-1890.
Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. N Engl J Med 2000;342:1937-1945.
Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-2158.
Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004;351:2481-2488.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237.
Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140-2150.
Hlatky MA. Evidence-based use of cardiac procedures and devices. N Engl J Med 2004;350:2126-2128.
Kadish A. SCD-HeFT and DEFINITE substudies: establishing a formative role for ICD therapy in the primary prevention of sudden death. New York: WebMD Medscape Health Network, 2004. (Accessed January 3, 2005, at http://www.medscape.com/viewarticle/496072.)
McClellan MB, Tunis SR. Medicare coverage of ICDs. N Engl J Med 2005;352:222-224.(Alan Kadish, M.D.)