Abstract & Commentary
Source: Hohnloser SH, et al. Prophylactic Use of An Implantable Cardioverter-Defibrillator After Acute Myocardial Infarction. N Engl J Med. 2004;351:2481-2488.
The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) examined the question whether prophylactic implantable cardioverter defibrillator (ICD) therapy begun soon after myocardial infarction would reduce long-term mortality. Patients were eligible for inclusion in the trial if they were younger than age 80 and had suffered a myocardial infarction within the previous 6 to 40 days. In addition, they were required to have a left ventricular ejection fraction of 0.35 or less, and either abnormal heart rate variability or an elevated baseline heart rate during 24-hour ambulatory ECG monitoring. Patients who had either undergone coronary artery bypass grafting or 3 vessel percutaneous coronary interventions after the infarction were excluded. In addition, patients who had sustained ventricular tachycardia or ventricular fibrillation more than 48 hours after the qualifying infarction were also excluded. Patients were randomized in a 1:1 ratio to receive either an ICD plus medical therapy or standard medical treatment only. The ICD chosen was a market-approved, single chamber ICD that was set with a tachycardia detection cut-off of 175 bpm. The bradycardia pacing setting was back-up VVI at 40 bpm. The primary end point was death from any cause. Death due to cardiac arrhythmia was a secondary end point.
The study group included 676 patients. About three quarters were men. The mean age was 62 ± 11 years. The index MI was anterior in 72%. The mean left ventricular ejection fraction was 0.28. During the index MI, 26% had received percutaneous coronary intervention only, 24% had received thrombolysis only, and 11% had received both percutaneous interventions and thrombolysis. At study entry, 87% of the patients were on beta adrenergic blockers, 94% were on angiotensin converting enzyme inhibitors, 92% were on antiplatelet agents, and 77% were on lipid lowering agents.
Among the 332 patients randomized to the ICD group, 20 patients refused to have one implanted and 2 patients died while awaiting the procedure. These patients were included in the ICD group in the intention-to-treat analysis used for the study. The average time between randomization and ICD implantation was 6.3 days ± 7.3 days. During an average observation period of 30 ± 13 months, 62 patients in the ICD group and 58 patients in the control group died. Life-table analysis showed no significant difference between the survival curves. The annual mortality rates were 7.5% in the ICD group and 6.9% in the control group. ICD therapy did effect the mode of death, as determined by an events committee. Among the 62 deaths in the ICD group, 12 were classified as due to arrhythmias, 34 were classified as cardiac but nonarrhythmic, and 16 were noncardiac. In the control group, there were 58 deaths, with 29 were due to arrhythmia, 20 classified as cardiac but nonarrhythmic, and 9 thought to be noncardiac. In-hospital device related complications were noted in 25 patients. These included lead dislodgement, pneumothorax, and inappropriate shocks.
Hohnloser and colleagues concluded that ICD therapy did not improve survival in high risk patients with recent myocardial infarction. Although there was a decrease in arrhythmia-related deaths in the ICD group, this effect was offset by a significant increase of equivalent magnitude in the rate of death from nonarrhythmic causes. The reason for this is uncertain, but it should be noted that in another defibrillator trial (The Multicenter Automatic Defibrillation Implantation Trial II), no effect was also seen in patients with the most recent infarctions
Comment by John P. DiMarco, MD, PhD
DINAMIT focused on a group of patients who have not been included in previous randomized trials of ICD therapy. There was clearly no benefit with ICD therapy in this trial, even though there was a marked reduction in the frequency of arrhythmic deaths. The reasons for this surprising observation are uncertain. In DINAMIT, patients were identified by both their low ejection fraction and either abnormal heart rate variability or an elevated baseline heart rate. The latter 2 are markers of persistent and ongoing heart failure, rather than solely risk for arrhythmia. It may be that in patients with this degree of heart failure, a treatment directed only at arrhythmias will have no or only minor effects on overall mortality. It should also be noted that the DINAMIT population was not particularly aggressively treated during the infarction that qualified them for the study. Only 35% of the patients enrolled received any mechanical revascularization. One-third received no acute revascularization, and an additional 25% received only thrombolysis. It is therefore possible that, in the absence of an aggressive revascularization strategy, recurrent ischemia and heart failure dominated the patients’ outcomes and overwhelmed any benefit from defibrillator therapy. It remains to be seen whether or not defibrillators would be of benefit in patients who are aggressively revascularized. The CABG-Patch Trial failed to show benefit in patients undergoing surgical revascularization, but in that study, early surgical mortality accounted for a large portion of the deaths.
The DINAMIT results leave cardiologists without an answer to a common clinical situation. We often identify high risk patients during the in-hospital phase after acute infarcts. DINAMIT suggests that ICD therapy, the most effective treatment we have to prevent sudden death, is of little benefit. Exactly how to manage these patients in this early phase after acute myocardial infarction, therefore, remains uncertain.
Dr. DiMarco, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville, is on the Editorial Board of Clinical Cardiology Alert.