Cited by 2,489Cardiac electrophysiology and arrhythmiasCardiac pacing and defibrillation studiesCardiac Arrhythmias and Treatments

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A Randomized Study of the Prevention of Sudden Death in Patients with Coronary Artery Disease

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Buxton, Alfred E., Lee, Kerry L., Fisher, John D., Josephson, Mark E., Prystowsky, Eric N., Hafley, Gail·1999·New England Journal of Medicine

DOI 10.1056/nejm199912163412503

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Abstract

BACKGROUND: Empirical antiarrhythmic therapy has not reduced mortality among patients with coronary artery disease and asymptomatic ventricular arrhythmias. Previous studies have suggested that antiarrhythmic therapy guided by electrophysiologic testing might reduce the risk of sudden death. METHODS: We conducted a randomized, controlled trial to test the hypothesis that electrophysiologically guided antiarrhythmic therapy would reduce the risk of sudden death among patients with coronary artery disease, a left ventricular ejection fraction of 40 percent or less, and asymptomatic, unsustained ventricular tachycardia. Patients in whom sustained ventricular tachyarrhythmias were induced by programmed stimulation were randomly assigned to receive either antiarrhythmic therapy, including drugs and implantable defibrillators, as indicated by the results of electrophysiologic testing, or no antiarrhythmic therapy. Angiotensin-converting-enzyme inhibitors and beta-adrenergic-blocking agents were administered if the patients could tolerate them. RESULTS: A total of 704 patients with inducible, sustained ventricular tachyarrhythmias were randomly assigned to treatment groups. Five-year Kaplan-Meier estimates of the incidence of the primary end point of cardiac arrest or death from arrhythmia were 25 percent among those receiving electrophysiologically guided therapy and 32 percent among the patients assigned to no antiarrhythmic therapy (relative risk, 0.73; 95 percent confidence interval, 0.53 to 0.99), representing a reduction in risk of 27 percent). The five-year estimates of overall mortality were 42 percent and 48 percent, respectively (relative risk, 0.80; 95 percent confidence interval, 0.64 to 1.01). The risk of cardiac arrest or death from arrhythmia among the patients who received treatment with defibrillators was significantly lower than that among the patients discharged without receiving defibrillator treatment (relative risk, 0.24; 95 percent confidence interval, 0.13 to 0.45; P<0.001). Neither the rate of cardiac arrest or death from arrhythmia nor the overall mortality rate was lower among the patients assigned to electrophysiologically guided therapy and treated with antiarrhythmic drugs than among the patients assigned to no antiarrhythmic therapy. CONCLUSIONS: Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease.

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“Randomized trials have shown that an ICD implantation can reduce mortality among patients with chronic ischemic heart disease and depressed LVEF.(3,4) Therefore, low LVEF is widely used to recommend ICD implantation as primary prevention of sudden death in patients with chronic ischemic heart disease.”
BackgroundInfluential
Antiarrhythmic agents and proarrhythmia
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“In high risk patients with nonsustained ventricular tachycardia, ICD implant was superior to amiodarone for primary prevention of sudden arrhythmic death in multicenter studies reported by Buxton et al (26) and Moss et al (27).”
Background
Ventricular arrhythmias in Chagas disease
Barbosa, M. P. T., do Carmo, A. A. L., Rocha, M. O. D. C., & Ribeiro, A. L. P. (2015) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/0037-8682-0003-2014 · Cited by 52
Extent of and Reasons for Nonuse of Implantable Cardioverter Defibrillator Devices in Clinical Practice Among Eligible Patients With Left Ventricular Systolic Dysfunction
LaPointe, N. M. A., Al‐Khatib, S. M., Piccini, J. P., Atwater, B. D., Honeycutt, E. F., Thomas, K. L., Shah, B. R., Zimmer, L. O., Sanders, G. D., & Peterson, E. D. (2011) · Circulation Cardiovascular Quality and Outcomes · doi:10.1161/circoutcomes.110.958603 · Cited by 52
Cost-Effectiveness of Primary Implanted Cardioverter Defibrillator for Sudden Death Prevention in Congestive Heart Failure
Chen, L., & Hay, J. W. (2004) · Cardiovascular Drugs and Therapy · doi:10.1023/b:card.0000029034.65769.f7 · Cited by 52
“Moreover, the MADIT [19] and MUSTT [20] trials showed that patients with coronary heart disease, reduced left ventricular ejection fraction (LVEF ≤ 40”
Method
Worldwide Utilization of Implantable Cardioverter/Defibrillators Now and in the Future
Seidl, K., & Senges, J. (2003) · Cardiac Electrophysiology Review · doi:10.1023/a:1023603118860 · Cited by 52
Female-Specific Education, Management, and Lifestyle Enhancement for Implantable Cardioverter Defibrillator Patients: The FEMALE-ICD Study: PSYCHOSOCIAL TREATMENT FOR WOMEN WITH ICDs
VAZQUEZ, L. D., CONTI, J. B., & SEARS, S. F. (2010) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2010.02787.x · Cited by 51
Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function
Aleong, R. G., Mulvahill, M., Halder, I., Carlson, N. E., Singh, M., Bloom, H. L., Dudley, S. C., Ellinor, P. T., Shalaby, A. A., Weiss, R., et al. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001566 · Cited by 51
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Impact of advanced age on survival in patients with implantable cardioverter defibrillators
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Self-citation
Management of Ventricular Arrhythmias Worldwide
Könemann, H., Ellermann, C., Zeppenfeld, K., & Eckardt, L. (2023) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2022.12.008 · Cited by 60
Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy
van Welsenes, G. H., Borleffs, C. J. W., van Rees, J. B., Atary, J. Z., Thijssen, J., van der Wall, E. E., & Schalij, M. J. (2010) · Netherlands Heart Journal · doi:10.1007/s12471-010-0047-3 · Cited by 49
Evolution of Cardiovascular Disease During the Transition to End-Stage Renal Disease
Bansal, N. (2017) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2016.12.002 · Cited by 52
Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
Kusumoto, F. M., Bailey, K. R., Chaouki, A. S., Deshmukh, A. J., Gautam, S., Kim, R. J., Kramer, D. B., Lambrakos, L. K., Nasser, N. H., & Sorajja, D. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.10.052 · Cited by 52
Right Ventricular Dysfunction and Long-Term Risk of Sudden Cardiac Death in Patients With and Without Severe Left Ventricular Dysfunction
Naksuk, N., Tan, N. Y. L., Padmanabhan, D., Kancharla, K., Makkar, N., Yogeswaran, V., Gaba, P., Kaginele, P., Riley, D. C., Sugrue, A. M., et al. (2018) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.117.006091 · Cited by 49
Implantable cardioverter defibrillators and their role in heart failure progression
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A multicentre, double-blind randomized crossover comparative study on the efficacy and safety of dofetilide vs sotalol in patients with inducible sustained ventricular tachycardia and ischaemic heart disease
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The Influence of Gender on Arrhythmias
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European Heart Rhythm Association/Heart Failure Association joint consensus document on arrhythmias in heart failure, endorsed by the Heart Rhythm Society and the Asia Pacific Heart Rhythm Society
Lip, G. Y. H., Heinzel, F. R., Gaïta, F., González‐Juanatey, J. R., Heuzey, J. Y. L., Potpara, T., Svendsen, J. H., Vos, M. A., Anker, S. D., Coats, A. J. S., et al. (2015) · European Journal of Heart Failure · doi:10.1002/ejhf.338 · Cited by 51
Systematic Review of Defibrillation Threshold Testing at De Novo Implantation
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“In the era of new electrophysiological strategies [33] and pharmacological approaches [34] for the treatment of life-threatening ventricular arrhythmias this is particularly promising.”
Background
Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial.
Raviele, A., Bongiorni, M. G., Brignole, M., Cappato, R., Capucci, A., Gaïta, F., Gulizia, M. M., Mangiameli, S., MONTENERO, A. S., & Pedretti, R. F. E. (2005) · EP Europace · doi:10.1016/j.eupc.2005.03.003 · Cited by 49
“In our patients with recent MI, we found a rate of induction of sustained ventricular arrhythmias by programmed electrical stimulation (32%) comparable with that reported in previous studies [8, 13 ].”
Result
New Approaches to Antiarrhythmic Therapy, Part II
Gambit, M. O. T. S. (2001) · Circulation · doi:10.1161/hc4901.099493 · Cited by 49
The history, science and innovation of Holter technology
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Arrhythmic and Mortality Outcomes Among Ischemic Versus Nonischemic Cardiomyopathy Patients Receiving Primary ICD Therapy
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Sudden Cardiac Death in Ischemic Heart Disease
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Electric Field Perturbations of Spiral Waves Attached to Millimeter-Size Obstacles
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Preventing tomorrow's sudden cardiac death today
Al‐Khatib, S. M., Sanders, G. D., Carlson, M. D., Cicic, A., Curtis, A. B., Fonarow, G. C., Groeneveld, P. W., Hayes, D. L., Heidenreich, P. A., Mark, D. B., et al. (2008) · American Heart Journal · doi:10.1016/j.ahj.2008.05.027 · Cited by 47
Self-citation
Effect of Drugs on Defibrillation Capacity
Dopp, A. L., Miller, J. M., & Tisdale, J. E. (2008) · Drugs · doi:10.2165/00003495-200868050-00004 · Cited by 48
Causes and prevention of sudden cardiac death in the elderly
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The current status of interventions aiming at reducing sudden cardiac death in dialysis patients
de Bie, M. K., van Dam, B., Gaasbeek, A., van Buren, M., van Erven, L., Bax, J. J., Schalij, M. J., Rabelink, T. J., & Jukema, J. W. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp185 · Cited by 47
Comparison of Defibrillation Efficacy and Survival Associated With Right Versus Left Pectoral Placement for Implantable Defibrillators
Gold, M. R., Shih, H.-T., Herre, J. M., Breiter, D. J., Zhang, Y., & Schwartz, M. (2007) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2007.02.087 · Cited by 47
Preventing tomorrow's sudden cardiac death today
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Self-citation
Guías de Práctica Clínica de la Sociedad Europea de Cardiología (ESC). Manejo del infarto agudo de miocardio en pacientes con elevación persistente del segmento ST
de Werf, F. V., Bax, J. J., Steg, P. G., Marco Tubaro, U., & Weis, M. (2009) · Revista Española de Cardiología · Cited by 46
Feasibility of Implantable Cardioverter Defibrillator Use in Elderly Patients:
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Outcome Studies with Device Therapy in Patients with Heart Failure
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Ventricular Tachycardia in Coronary Artery Disease
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Self-citation

Authors: Buxton, A. E., Lee, K. L., Fisher, J. D., Josephson, M. E., Prystowsky, E. N., & Hafley, G.
Affiliations: Brown University (US)
Duke University (US)
Albert Einstein College of Medicine (US)
Beth Israel Deaconess Medical Center (US)
ORCID: Buxton, Alfred E.
Lee, Kerry L.
Fisher, John D.
Prystowsky, Eric N.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 1999-12-16
Volume: 341
Issue: 25
Pages: 1882-1890
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejm199912163412503
OpenAlex: W2313547185
Cited by: 2,489
References: 34
Citations by year: 2026: 20 · 2025: 36 · 2024: 23 · 2023: 34 · 2022: 44 · 2021: 41 · 2020: 51 · 2019: 54 · 2018: 54 · 2017: 92 · 2016: 75 · 2015: 87 · 2014: 95 · 2013: 114 · 2012: 122
FWCI: 70.29
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5u01hl045726-06)
National Heart, Lung, and Blood Institute (UO1HL45700, UO1-HL45726, U01HL045700)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
Keywords: coronary artery disease, asymptomatic ventricular arrhythmia, implantable cardioverter-defibrillator, antiarrhythmic drugs, electrophysiologic testing, programmed electrical stimulation, cardiac arrest, all-cause mortality, left ventricular ejection fraction, ACE inhibitors, beta-blockers
MeSH terms: Aged, Anti-Arrhythmia Agents, Cardiac Pacing, Artificial, Coronary Disease, Electrophysiology, Female, Humans, Male, Middle Aged, Survival Analysis, Death, Sudden, Cardiac, Defibrillators, Implantable, Tachycardia, Ventricular

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A Randomized Study of the Prevention of Sudden Death in Patients with Coronary Artery Disease

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