DINAMIT: The Defibrillator in Acute Myocardial Infarction Trial

Luis Gruberg, MD, FACC

Disclosures

April 16, 2004

Editorial Collaboration

Medscape &

Presenter: Stuart J. Connolly, MD, McMaster University (Hamilton, Ontario, CANADA) and Stefan H. Hohnloser, MD, J.W. Goethe University (Frankfurt, Germany)

Large randomized clinical trials have definitively shown that the use of an implantable cardioverter defibrillator (ICD) is effective for both the primary and secondary prevention of sudden death across a large population of patients. The primary prevention trials, such as Multicenter Unsustained Tachycardia Trial (MUSTT)[1] and the first and second Multicenter Automatic Defibrillator Implantation Trial (MADIT I and II),[2,3] studied the effects of ICDs in post-myocardial infarction (MI) patients with poor left ventricular function. However, the majority of patients studied in these primary prevention trials included those who had experienced an MI more than 6 months prior to enrollment.

Nevertheless, mortality rates 1 year post-MI continue to be high, and it has been estimated that as many as 40% of these deaths are arrhythmic in nature. It is therefore reasonable to hypothesize that ICDs could improve survival in patients early after MI. Currently, there are no randomized controlled trials that have assessed the prophylactic use of ICDs in this patient population.

Study Design

The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) was an open, multicenter, randomized, prospective study designed to assess the impact of ICD implantation on top of optimal medical therapy (OMT) vs OMT alone on all-cause mortality in high-risk patients within 40 days after MI.

Inclusion Criteria
  • Occurrence of MI 6 to 40 days prior to enrollment

  • Left ventricular ejection fraction (LVEF) ≤ 35%

  • Signs of impaired cardiac autonomic modulation

    • Depressed standard deviation of sinus RR intervals ≤ 70 ms

    • Elevated heart rate (mean RR interval ≤ 750 ms)

Exclusion Criteria
  • New York Heart Association class IV heart failure

  • Significant noncardiac disease limiting life expectancy to < 2 years

  • Coronary artery bypass graft surgery performed since index MI

  • 3-vessel percutaneous coronary intervention performed since index MI

  • Sustained ventricular tachycardia/ventricular fibrillation occurring > 48 hours after index MI

Primary Endpoint
  • All-cause mortality

Secondary Endpoints
  • Arrhythmic death

  • Quality of life

All-deaths were adjudicated blindly as to the cause of death and readings from the ICD were not taken into account. Adjudicators were not aware of whether the patient had an ICD or not, so all deaths were based on clinical features.

Methods

Patients were screened at 73 centers in 10 countries . Of the 1016 patients who met entry criteria, 674 (66%) agreed to enrollment and were randomized to either OMT plus ICD therapy (n = 332) or OMT alone (control, n = 342).

Results

Both groups had similar baseline characteristics (Table 1). The majority of patients were male, mean age was 62 years, of note, one third of patients had previous MI prior to their index MI and 20% of all patients had undergone prior revascularization. Seventy-two percent of infarcts were anterior and, as indicated by peak creatine kinase levels (average 2300 IU/L), they were large in size. Approximately half of all patients presented with clinical signs of congestive heart failure in the early days of infarction, and balloon pump use was deemed necessary by the investigators for 6% of patients. Very few patients had an indication for permanent pacing.

Table 1. DINAMIT: Baseline Characteristics
  ICD (n = 332) Control (n = 342)
Age (yrs) 62 62
Male (%) 76 77
Diabetes (%) 31 29
Hypertension (%) 47 45
Prior infarction (%) 37 33
Prior PCI (%) 15 11
Anterior wall infarction (%) 72 72
Peak CK (IU/L) 2329 2138
CHF with index infarction (%) 52 52
Mechanical ventilation (%) 10 10
Balloon pump (%) 6 6
Reperfusion (%) 64 66
PCI only (%) 42 43
Thrombolysis only %) 42 36
Both (%) 16 21
No reperfusion (%) 36 34
Ejection fraction (%) 28 +/- 5 29 +/- 13
CHF, congestive heart failure; CK, creatine kinase; ICD, implantable cardioverter defibrillator; PCI, percutaneous coronary intervention

All patients were on OMT at baseline, which consisted of high prescription rates of beta-blockers (87%), angiotensin-converting enzyme inhibitors (95%), lipid-lowering therapy (77% to 80%), and antiplatelet agents (92%). At follow-up (average 30 months), there was little change in OMT and patient compliance remained high (Table 2).

Table 2. DINAMIT: Pharmacologic Therapy at Baseline and Follow-up
  ICD (n = 332) Control (n = 342)
  Baseline Follow-up Baseline Follow-up
Beta-blockers (%) 87 82 87 82
ACE inhibitors (%) 95 91 95 87
Lipid-lowering drugs (%) 77 75 80 78
Antiplatelet agents (%) 92 80 92 78
ACE, angiotensin converting enzyme; ICD, implantable cardioverter defibrillator

There was no significant difference in the number of deaths from all-cause mortality between the 2 groups. A total of 120 deaths occurred, 58 (6.9%) in the control group vs 62 (7.5%) in ICD patients (P = .66). However, the risk of arrhythmic death was significantly lower in patients randomized to the ICD arm of the study than in the control group (12 [1.5%] vs 29 [3.5%], respectively; P = .009). Overall, ICD therapy reduced the cumulative risk of arrhythmic death by 58% (95% CI, 0.22-0.83) compared with control. This reduced risk of arrhythmic death in the ICD arm was offset by an increase in nonarrhythmic death compared with control (6.1% vs 3.5%, P = .016) (Figure). Kaplan-Meier curves for the cumulative risk of nonarrhythmic death began to diverge between 5 and 6 months and continued throughout the follow-up period. The majority of nonarrhythmic deaths were reportedly cardiovascular in nature.

Figure. DINAMIT: Primary analysis of all-cause, arrhythmic, and nonarrhythmic mortality.
Conclusions

On the basis of the results of the DINAMIT study, investigators concluded the following:

  1. ICD therapy did not reduce mortality in high-risk patients early after MI.

  2. The ICD significantly reduced arrhythmic death by more than 50%; however, this was offset by a significant increase in nonarrhythmic death.

  3. It may be that the use of an ICD in patients early after MI changes the mode of death from arrhythmic to nonarrhythmic.

  4. Myocardial ischemia may play a decisive role in the present findings.

  5. Study defines a limitation of prophylactic ICD implantation.

References
  1. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med. 1999;341:1882-1890.

  2. Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med. 1996;335:1933-1940.

  3. Moss AJ, Zareba W, Hall WJ, et al, for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation on a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-883.

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