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A Randomized Study of the Prevention of Sudden Death in Patients with Coronary Artery Disease
Open accessAbstract
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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“Following the Multicenter Unsustained Tachycardia Trial (MUSTT) (Buxton et al., 1999), there is a role for AECG for NSVT detection in post-MI patients with LVEF 35%-40% as electrophysiologically guided ICD implantation improves survival”
From 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry (2017) · cites this paper as Buxton et al., 1999
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“NSVT accompanied by inducibility of sustained VT during programmed ventricular stimulation was associated with an increased risk of SCD”
From 2017 ISHNE-HRS expert consensus statement on ambulatory ECG and external cardiac monitoring/telemetry (2017) · cites this paper as Buxton et al., 1999
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“ABBREVIATIONS LIST CC American College of Cardiology CCF American College of Cardiology Foundation F Atrial fibrillation HA American Heart Association MI Acute myocardial infarction MIOVIRT Amiodarone Versus Implantable Defibrillator in Patients with Nonischemic Cardiomyopathy and Asymptomatic Nonsustained Ventricular…”
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Preventing ventricular fibrillation by flattening cardiac restitution
Garfinkel, A., Kim, Y., Voroshilovsky, O., Qu, Z., Kil, J. R., Lee, M., Karagueuzian, H. S., Weiss, J. N., & Chen, P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090492697 · Cited by 531
Goldenberg, I., Vyas, A. K., Hall, W. J., Moss, A. J., Wang, H., He, H., Zaręba, W., McNitt, S. A., & Andrews, M. L. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.08.058 · Cited by 530
Zipes, D. P., Camm, A. J., Borggrefe, M. M., Buxton, A. E., CHAITMAN, B. R., FROMER, M. A., Gregoratos, G., Klein, G. J., Moss, A. J., Myerburg, R. J., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl199 · Cited by 519
Self-citationInfarct morphology identifies patients with substrate for sustained ventricular tachycardia
Bello, D. B., Fieno, D. S., Kim, R. J., Pereles, F. S., PASSMAN, R. S., Song, G. K., Kadish, A. H., & Goldberger, J. J. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.12.057 · Cited by 471
Body Mass Index and Risk, Age of Onset, and Survival in Patients With Pancreatic Cancer
Li, D. (2009) · JAMA · doi:10.1001/jama.2009.886 · Cited by 474
Epstein, A. E., Dimarco, J., Ellenbogen, K. A., Estes, N. A. M., Freedman, R. A., Gettes, L. S., Gillinov, A. M., Gregoratos, G., Hammill, S. C., Hayes, D. L., et al. (2008) · Heart Rhythm · doi:10.1016/j.hrthm.2008.04.015 · Cited by 462
“Abbreviations List ACC American College of Cardiology ACCF American College of Cardiology Foundation AHA American Heart Association AV Atrioventricular CRT Cardiac resynchronization therapy DDD Dual-chamber pacemaker that senses/paces in the atrium/ventricle and is inhibited/triggered by intrinsic rhythm LVEF Left ven…”
Inappropriate Implantable Cardioverter-Defibrillator Shocks
van Rees, J. B., Borleffs, C. J. W., de Bie, M. K., Stijnen, T., van Erven, L., Bax, J. J., & Schalij, M. J. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.06.059 · Cited by 449
Vassallo, P., & Trohman, R. G. (2007) · JAMA · doi:10.1001/jama.298.11.1312 · Cited by 449
Value of Programmed Ventricular Stimulation After Tetralogy of Fallot Repair
Khairy, P., Landzberg, M. J., Gatzoulis, M. Α., Lucron, H., Lambert, J., Marçon, F., Alexander, M. E., & Walsh, E. P. (2004) · Circulation · doi:10.1161/01.cir.0000126495.11040.bd · Cited by 435
The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes
Dzau, V. J., Antman, E. M., Black, H. R., Hayes, D. L., Manson, J. E., Plutzky, J., Popma, J. J., & Stevenson, W. G. (2006) · Circulation · doi:10.1161/circulationaha.106.655688 · Cited by 455
Goldberger, J. J., CAIN, M. E., Hohnloser, S. H., Kadish, A. H., Knight, B. P., Lauer, M. S., Maron, B. J., Page, R. L., PASSMAN, R. S., Siscovick, D. S., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.05.003 · Cited by 432
Significance of QRS Complex Duration in Patients With Heart Failure
Kashani, A., & Barold, S. S. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.01.071 · Cited by 422
Hernandez, A. F., Fonarow, G. C., Liang, L., Al‐Khatib, S. M., Curtis, L. H., LaBresh, K. A., Yancy, C. W., Albert, N. M., & Peterson, E. D. (2007) · JAMA · doi:10.1001/jama.298.13.1525 · Cited by 419
Al-Khatib, S. M., Stevenson, W. G., Ackerman, M. J., Bryant, W. J., Callans, D. J., Curtis, A. B., Deal, B. J., Dickfeld, T., Field, M. E., Fonarow, G. C., et al. (2018) · Circulation · doi:10.1161/cir.0000000000000548 · Cited by 412
QRS duration and mortality in patients with congestive heart failure
Iuliano, S., Fisher, S. G., Karasik, P., Fletcher, R. D., & Singh, S. N. (2002) · American Heart Journal · doi:10.1067/mhj.2002.122516 · Cited by 403
Desai, A. S., Fang, J. C., Maisel, W. H., & Baughman, K. L. (2004) · JAMA · doi:10.1001/jama.292.23.2874 · Cited by 403
Navigating the Crossroads of Coronary Artery Disease and Heart Failure
Gheorghiade, M., Sopko, G. S., Luca, L. D., Velazquez, E. J., Parker, J. D., Binkley, P. F., Sadowski, Z., Golba, K. S., Prior, D., Rouleau, J. L., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.623199 · Cited by 405
Brugada, J., Blom, N. A., Sarquella‐Brugada, G., Blomström‐Lundqvist, C., Deanfield, J. E., Janoušek, J., Abrams, D. J., Bauersfeld, U., Brugada, R., Drago, F., et al. (2013) · EP Europace · doi:10.1093/europace/eut082 · Cited by 397
“– 301 Large randomized primary prevention trials in adults with heart failure also showed a survival benefit from ICD implantation.(292) – 294 Guidelines for primary prevention in children and CHD patients (see below) are currently in a rudimentary state due to the absence of any randomized trials or large observation…”
BackgroundBerul, C. I., Hare, G. F. V., Kertesz, N. J., Dubin, A. M., Cecchin, F., Collins, K. K., Cannon, B. C., Alexander, M. E., Triedman, J. K., Walsh, E. P., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.01.033 · Cited by 398
Electrical Storm Presages Nonsudden Death
Exner, D. V., Pinski, S. L., Wyse, D. G., Renfroe, E. G., Follmann, D. A., Gold, M. R., Beckman, K. J., Coromilas, J., Lancaster, S. E., & Hallstrom, A. P. (2001) · Circulation · doi:10.1161/01.cir.103.16.2066 · Cited by 390
Increasing rates of cardiac device infections among medicare beneficiaries: 1990–1999
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Epstein, A. E., Dimarco, J., Ellenbogen, K. A., Estes, N. A. M., Freedman, R. A., Gettes, L. S., Gillinov, A. M., Gregoratos, G., Hammill, S. C., Hayes, D. L., et al. (2008) · Circulation · doi:10.1161/circualtionaha.108.189741 · Cited by 366
Percent right ventricular pacing predicts outcomes in the DAVID trial
Sharma, A. D., Rizo-Patrón, C., Hallstrom, A. P., O’Neill, G., Rothbart, S. T., Martins, J. B., Roelke, M., Steinberg, J. S., & Greene, H. L. (2005) · Heart Rhythm · doi:10.1016/j.hrthm.2005.05.015 · Cited by 365
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“We and others have used the Hinkle-Thaler approach for lassifying SCDs subcategorized by the degree of LV dysfuncion (1,2,5).”
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Self-citationBuxton, A. E., Lee, K. L., Hafley, G. E., Pires, L. A., Fisher, J. D., Gold, M. R., Josephson, M. E., Lehmann, M. H., & Prystowsky, E. N. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.04.095 · Cited by 356
Self-citationT-Wave Alternans and the Susceptibility to Ventricular Arrhythmias
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Russo, A. M., Stainback, R. F., Bailey, S. R., Epstein, A. E., Heidenreich, P. A., Jessup, M. L., Kapa, S., Kremers, M. S., Lindsay, B. D., & Stevenson, L. W. (2013) · Heart Rhythm · doi:10.1016/j.hrthm.2013.01.008 · Cited by 348
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“Following the Multicenter Unsustained Tachycardia Trial (MUSTT) (Buxton et al., 1999), there is a role for AECG for NSVT detection in post-MI patients with LVEF 35%–40% as electrophysiologically guided ICD implantation improves survival (Epstein et al.”
BackgroundMethodWilkoff, B. L., Fauchier, L., Stiles, M. K., Morillo, C. A., Al-Khatib, S. M., Almendral, J., Aguinaga, L., Berger, R. D., Cuesta, A., Daubert, J. P., et al. (2016) · Heart Rhythm · doi:10.1016/j.hrthm.2015.11.018 · Cited by 301
Sudden Cardiac Death: Exploring the Limits of Our Knowledge
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Linde, C. M., Bongiorni, M. G., Birgersdotter-Green, U. M., Curtis, A. B., Deisenhofer, I., Furokawa, T., Gillis, A. M., Haugaa, K. H., Lip, G. Y. H., Gelder, I. C. V., et al. (2018) · EP Europace · doi:10.1093/europace/euy067 · Cited by 308
NON‐CORONARY HEART DISEASE IN DIALYSIS PATIENTS: Sudden Cardiac Death and Dialysis Patients
Herzog, C. A., Mangrum, J. M., & PASSMAN, R. S. (2008) · Seminars in Dialysis · doi:10.1111/j.1525-139x.2008.00455.x · Cited by 290
Implantable Cardioverter–Defibrillators
Dimarco, J. (2003) · New England Journal of Medicine · doi:10.1056/nejmra035432 · Cited by 294
Guidelines for cardiac pacing and cardiac resynchronization therapy
Vardas, P. E., Auricchio, A., Blanc, J., Daubert, J., Drexler, H., Ector, H., Gasparini, M., Linde, C. M., Morgado, F. B., Oto, A., et al. (2007) · EP Europace · doi:10.1093/europace/eum189 · Cited by 290
2013 ACCF/AHA Guideline for the Management of Heart Failure: Executive Summary
Yancy, C. W., Jessup, M. L., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., Fonarow, G. C., Geraci, S. A., Horwich, T. B., Januzzi, J. L., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.020 · Cited by 297
Wearable Cardioverter–Defibrillator after Myocardial Infarction
Olgin, J. E., Pletcher, M. J., Vittinghoff, E., Wranicz, J. K., Malik, R. K., Morin, D. P., ZWEIBEL, S. L., Buxton, A. E., Elayi, C. S., Chung, E. H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1800781 · Cited by 288
Self-citation
Metadata
- 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)
- 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
- 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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