Mechanisms Underlying the Lack of Effect of Implantable Cardioverter-Defibrillator Therapy on Mortality in High-Risk Patients With Recent Myocardial Infarction: Insights from the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT).
Summary of "Mechanisms Underlying the Lack of Effect of Implantable Cardioverter-Defibrillator Therapy on Mortality in High-Risk Patients With Recent Myocardial Infarction: Insights from the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT)."
Background- Although implantable cardioverter-defibrillators (ICDs) lower mortality in stable patients with low ejection fraction late after myocardial infarction, randomized trials of ICD versus control subjects implanted early after myocardial infarction do not show mortality benefit. Our objective was to investigate possible mechanisms underlying the lack of mortality benefit in the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT). Methods and Results- This is a secondary analysis of the prospective randomized clinical trial. Outpatients with recent (6 to 40 days) acute myocardial infarction, left ventricular dysfunction (ejection fraction <35%), and low heart rate variability were randomized to ICD (n=311) or to standard medical therapy (n=342). In a competing-risks analysis, those factors that increased the risk of arrhythmic death also increased the risk of nonarrhythmic deaths. After adjustment for these factors, receiving an ICD was associated with a decreased risk of arrhythmic death (hazard ratio, 0.33; 95% confidence interval, 0.15 to 0.71) but an increase in nonarrhythmic death (hazard ratio, 1.70; 95% confidence interval, 1.00 to 2.80). In an adjusted time-dependent analysis, patients receiving an ICD and having appropriate ICD therapy had a 15.1% yearly hazard of mortality compared with 5.2% in ICD patients with no appropriate therapy (P<0.001). The reduction in sudden death in ICD patients was completely offset by increased nonarrhythmic deaths, which were greatest in patients receiving ICD shock therapy (hazard ratio, 6.0; 95% confidence interval, 2.8 to 12.7). Conclusions- In patients receiving ICDs early after myocardial infarction, those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death, negating the benefit of ICDs in this setting.
Affiliation
St. Michael's Hospital, 30 Bond St, 6-050Q, Toronto, Ontario, M5B 1W8, Canada. dorianp@smh.toronto.on.ca.
Journal Details
This article was published in the following journal.
Name: Circulation
ISSN: 1524-4539
Pages: 2645-52
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21135366
- DOI: http://dx.doi.org/10.1161/CIRCULATIONAHA.109.924225
Medical and Biotech [MESH] Definitions
Cardiac Resynchronization Therapy Devices
Types of artificial pacemakers with implantable leads to be placed at multiple intracardial sites. They are used to treat various cardiac conduction disturbances which interfere with the timing of contraction of the ventricles. They may or may not include defibrillating electrodes (IMPLANTABLE DEFIBRILLATORS) as well.
Drug Therapy, Combination
Therapy with two or more separate preparations given for a combined effect.
Defibrillators, Implantable
Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.
Behavior And Behavior Mechanisms
The observable response made to a situation and the unconscious processes underlying it.
Dichlororibofuranosylbenzimidazole
An RNA polymerase II transcriptional inhibitor. This compound terminates transcription prematurely by selective inhibition of RNA synthesis. It is used in research to study underlying mechanisms of cellular regulation.
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