A Randomized Study of the Prevention of Sudden Death in Patients with Coronary Artery Disease
Alfred E. Buxton, M.D., Kerry L. Lee, Ph.D., John D. Fisher, M.D., Mark E. Josephson, M.D., Eric N. Prystowsky, M.D., Gail Hafley, M.S., for The Multicenter Unsustained Tachycardia Trial Investigators
Background Empirical antiarrhythmic therapy has not reducedmortality among patients with coronary artery disease and asymptomaticventricular arrhythmias. Previous studies have suggested thatantiarrhythmic therapy guided by electrophysiologic testingmight reduce the risk of sudden death.
Methods We conducted a randomized, controlled trial to testthe hypothesis that electrophysiologically guided antiarrhythmictherapy would reduce the risk of sudden death among patientswith coronary artery disease, a left ventricular ejection fractionof 40 percent or less, and asymptomatic, unsustained ventriculartachycardia. Patients in whom sustained ventricular tachyarrhythmiaswere induced by programmed stimulation were randomly assignedto receive either antiarrhythmic therapy, including drugs andimplantable defibrillators, as indicated by the results of electrophysiologictesting, or no antiarrhythmic therapy. Angiotensin-convertingenzymeinhibitors and beta-adrenergicblocking agents were administeredif the patients could tolerate them.
Results A total of 704 patients with inducible, sustained ventriculartachyarrhythmias were randomly assigned to treatment groups.Five-year KaplanMeier estimates of the incidence of theprimary end point of cardiac arrest or death from arrhythmiawere 25 percent among those receiving electrophysiologicallyguided therapy and 32 percent among the patients assigned tono antiarrhythmic therapy (relative risk, 0.73; 95 percent confidenceinterval, 0.53 to 0.99), representing a reduction in risk of27 percent. The five-year estimates of overall mortality were42 percent and 48 percent, respectively (relative risk, 0.80;95 percent confidence interval, 0.64 to 1.01). The risk of cardiacarrest or death from arrhythmia among the patients who receivedtreatment with defibrillators was significantly lower than thatamong the patients discharged without receiving defibrillatortreatment (relative risk, 0.24; 95 percent confidence interval,0.13 to 0.45; P<0.001). Neither the rate of cardiac arrestor death from arrhythmia nor the overall mortality rate waslower among the patients assigned to electrophysiologicallyguided therapy and treated with antiarrhythmic drugs than amongthe patients assigned to no antiarrhythmic therapy.
Conclusions Electrophysiologically guided antiarrhythmic therapywith implantable defibrillators, but not with antiarrhythmicdrugs, reduces the risk of sudden death in high-risk patientswith coronary disease.
Source Information
From the Department of Medicine, Brown University School of Medicine and Rhode Island Hospital, Providence (A.E.B.); Duke University Clinical Research Institute, Durham, N.C. (K.L.L., G.H.); the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, N.Y. (J.D.F.); the Department of Medicine, Beth Israel Deaconess Medical Center, Boston (M.E.J.); and Care Group, Indianapolis (E.N.P.).
Address reprint requests to Dr. Buxton at the Division of Cardiology, Rhode Island Hospital, 2 Dudley St., Suite 360, Providence, RI 02905.
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Gibson, D. P., Kuntz, K. K., Levenson, J. L., Ellenbogen, K. A.
(2008). Decision-making, emotional distress, and quality of life in patients affected by the recall of their implantable cardioverter defibrillator. Europace
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Berul, C. I., Van Hare, G. F., Kertesz, N. J., Dubin, A. M., Cecchin, F., Collins, K. K., Cannon, B. C., Alexander, M. E., Triedman, J. K., Walsh, E. P., Friedman, R. A.
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Koller, M. T., Schaer, B., Wolbers, M., Sticherling, C., Bucher, H. C., Osswald, S.
(2008). Death Without Prior Appropriate Implantable Cardioverter-Defibrillator Therapy: A Competing Risk Study. Circulation
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Daubert, J. P., Zareba, W., Cannom, D. S., McNitt, S., Rosero, S. Z., Wang, P., Schuger, C., Steinberg, J. S., Higgins, S. L., Wilber, D. J., Klein, H., Andrews, M. L., Hall, W. J., Moss, A. J., for the MADIT II Investigators,
(2008). Inappropriate Implantable Cardioverter-Defibrillator Shocks in MADIT II: Frequency, Mechanisms, Predictors, and Survival Impact. J Am Coll Cardiol
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Albert, N. M., Lewis, C.
(2008). Recognizing and Managing Asymptomatic Left Ventricular Dysfunction: After Myocardial Infarction. Crit Care Nurse
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Wellens, H. J.
(2008). Forty Years of Invasive Clinical Electrophysiology: 1967-2007. Circ Arrhythm Electrophysiol
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Elgarhi, N, Kreuz, J, Balta, O, Nickenig, G, Hoium, H, Lewalter, T, Schwab, J O.
(2008). Significance of Wedensky Modulation testing in the evaluation of non-invasive risk stratification for ventricular tachyarrhythmia in patients with coronary artery disease and implantable cardioverter-defibrillator. Heart
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Scott, P.A., Gorman, S., Andrews, N.P., Roberts, P.R., Kalra, P.R.
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Gardiwal, A., Yu, H., Oswald, H., Luesebrink, U., Ludwig, A., Pichlmaier, A. M., Drexler, H., Klein, G.
(2008). Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator. Europace
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Travin, M. I.
(2008). A Potential Key Role for Radionuclide Imaging in the Prediction and Prevention of Sudden Arrhythmic Cardiac Death. JNM
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DeMaria, A. N., Bax, J. J., Ben-Yehuda, O., Clopton, P., Feld, G. K., Ginsburg, G. S., Greenberg, B. H., Knoke, J. D., Lew, W. Y.W., Lima, J. A.C., Maisel, A. S., Narayan, S. M., Narula, J., Sahn, D. J., Tsimikas, S.
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Goldenberg, I., Vyas, A. K., Hall, W. J., Moss, A. J., Wang, H., He, H., Zareba, W., McNitt, S., Andrews, M. L., for the MADIT-II Investigators,
(2008). Risk Stratification for Primary Implantation of a Cardioverter-Defibrillator in Patients With Ischemic Left Ventricular Dysfunction. J Am Coll Cardiol
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Mittal, S.
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Anstadt, M. P., Lowe, J. E.
(2008). Cardiopulmonary Resuscitation. Card Surg Adult
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Kuhne, M., Schaer, B., Moulay, N., Sticherling, C., Osswald, S.
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