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Danish Trial in Acute Myocardial Infarction-2 - DANAMI-2
Contribution To Literature:
The DANAMI-2 trial showed that interhospital transport for primary PCI was superior to fibrinolysis.
Description:
The goal of the trial was to evaluate thrombolytic vs. invasive therapy in patients with acute myocardial infarction (MI).
Study Design
Patients Enrolled: 1,572
Mean Follow-Up: 30 days
Mean Patient Age: median age, 63 years
Female: 27%
Inclusion Criteria:
ST elevation >4 mm symptom onset ≥30 minutes and ≤12 hours; no upper age limit
Exclusions:
Age <18 years; thrombolytic treatment within the last 30 days acute MI within the last 30 days; high risk during transportation (cardiogenic shock or severe heart failure with hypotension, persistent life-threatening arrhythmias or need for mechanical ventilation); LBBB; any cardiac condition requiring immediate surgical intervention; severe valvular or pericardial disease; severe noncardiac disease (life expectancy <12 months); active bleeding or bleeding diathesis; history of stroke in the past 3 months; major surgery or significant trauma in the past 1 month; severe hypertension after initial treatment (systolic >200 mm Hg or diastolic >110 mm Hg); expected time between randomization and arrival in the catheterization laboratory >3 hours for patients randomized in referral hospitals and >2 hours for patients randomized in invasive hospitals; infection with sepsis; aortic aneurysm with thrombus diagnosed previously; no femoral pulse or known difficulty with arterial access or bilateral femoral vascular grafts; previous coronary bypass grafting; severe renal failure; NIDDM treated with metformin within the last 48 hours; patients in whom compliance with follow-up is doubtful or unlikely; pregnancy or lactation and females of childbearing potential not using adequate birth control.
Primary Endpoints:
Composite of death from any cause, clinical reinfarction, or disabling stroke at 30 days; procedure-related reinfarction was not included in the primary endpoint.
Secondary Endpoints:
Composite endpoint of mortality + clinical reinfarction + significant disabling stroke at end of study period. Total mortality at end of study period. Cardiac mortality at end of study period. Angina pectoris free survival without AMI at end of study period. Quality of life at follow-up after 30 days, 1 year, 3 years and 5 years. Costs analysis at follow-up after 30 days, 1 year, 3 years and 5 years.
Drug/Procedures Used:
Patients were randomized to primary PCI or front loaded tPA - 15 mg bolus over 1-3 minutes + infusion of 0.75 mg/kg over 30 minutes (not to exceed 50 mg) + 0.5 mg/kg over 60 minutes (not to exceed 35 mg) Patients randomized to PCI were transferred to referring center if catheterization lab facilities were not available on-site.
Concomitant Medications:
Aspirin (300 mg initially followed by 75-150 mg daily) Heparin (5000 U bolus + 1000 U/hr infusion for at least 48 hours in patients randomized to tPA; 10,000 U bolus + additional heparin to keep the ACT between 350-450 seconds during procedure in patients randomized to PCI)
Principal Findings:
The trial was stopped early by the Safety and Efficacy Committee after a benefit in the composite endpoint was observed in the PCI arm in the referral-hospital substudy.
The composite event rate occurred in 8.0% of patients who received PCI and 13.7% of fibrinolysis patients (p=0.0003). When the analysis was stratified by type of enrolling hospital (referral vs. on-site cath lab), similar results were observed: composite rate of 14.2% with fibrinolytic vs. 8.5% with PCI (p=0.002, RRR 40%) at referral hospitals and 12.3% with fibrinolytic vs. 6.7% with PCI at tertiary centers (p=0.05, RRR 45%).
The composite endpoint was driven by a reduction in recurrent MI (6.3% vs. 1.6%, p<0.0001). There was no difference in death at 30 days: 7.8% in the fibrinolysis group vs. 6.6% in the PCI group (p=0.35) or disabling stroke: 2.0% vs. 1.1% (p=0.15), respectively. The time from randomization to balloon inflation was 112 minutes in the referral center patients and 91 minutes in the on-site patients, a 21-minute difference. Rescue angioplasty was performed in 1.9% of patients in the thrombolysis arm (15/782).
16-Year Follow-Up:
- Death or re-infarction: 58.7% of the PCI group vs. 62.3% of the fibrinolysis group (p < 0.05)
- Re-infarction: 19.0% of the PCI group vs. 24.5% of the fibrinolysis group (p < 0.05)
Interpretation:
Among patients with acute MI, treatment with primary PCI was associated with a reduction in the primary endpoint of death, clinical reinfarction, or stroke compared with thrombolytic therapy. The primary endpoint in the trial was driven primarily by a reduction in the risk of recurrent MI among patients treated by primary PCI. This benefit was sustained to 16 years. This study confirms that thrombolysis is associated with a high rate of reinfarction.
Trials such as ASSENT 3 and the TIMI 23/ENTIRE study demonstrated that antithrombotic agents such as enoxaparin may further reduce the rates of reinfarction among patients treated with thrombolysis. The present trial does not shed light on the concept of "facilitated PCI" where a drug would be given before the PCI to improve pre-PCI patency rates. Patients were brought directly to the coronary care unit by the ambulance staff and were not processed through the emergency department, and transfer patients were transported by the same ambulance staff directly to the referral center, resulting in a door-to-balloon time of only 91 minutes in the tertiary centers and 112 minutes in the transfer centers, much lower than 110 minutes and 185 minute times, respectively, that was reported in US patients from the NRMI 4 study.
References:
Thrane PG, Kristensen SD, Olesen KKW, et al. 16-year follow-up of the Danish Acute Myocardial Infarction 2 (DANAMI-2) trial: primary percutaneous coronary intervention vs. fibrinolysis in ST-segment elevation myocardial infarction. Eur Heart J 2020;41:847-54.
Editorial Comment: Ibanez B. And fibrinolysis became pharmacoinvasive. Eur Heart J 2020;41:855-7.
Presented by Dr. Pernille Gro Thrane at the European Society of Cardiology Congress, Paris, France, September 2, 2019.
Andersen HR, Nielsen TT, Rasmussen K, et al., on behalf of the DANAMI-2 Investigators. A Comparison of Coronary Angioplasty With Fibrinolytic Therapy in Acute Myocardial Infarction. N Engl J Med 2003;349:733-42.
Presented at ACC 51st Scientific Session, Atlanta, GA, March 2002.
Keywords: ESC Congress, ESC 19, Acute Coronary Syndrome, Thrombolytic Therapy, Stroke, Myocardial Infarction, Patient Transfer, Coronary Care Units, Referral and Consultation, Emergency Service, Hospital, Fibrinolytic Agents, Angioplasty, Enoxaparin, Fibrinolysis, Catheterization, Tissue Plasminogen Activator
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