DANAMI-2: Primary PCI in Acute Myocardial Infarction (2003)

“We conclude that interhospital transfer of patients with STEMI for primary PCI is superior to on-site fibrinolysis.”

  • The DANAMI-2 Investigators

1. Publication Details

  • Trial Title: Primary Angioplasty versus Fibrinolysis for ST-Segment-Elevation Myocardial Infarction
  • Citation: Andersen HR, Nielsen TT, Rasmussen K, et al. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med. 2003;349(8):733-742. DOI: 10.1056/NEJMoa025142
  • Published: August 21, 2003, in The New England Journal of Medicine
  • Author: Henning R. Andersen, M.D., D.M.Sc.
  • Funding: The Danish Heart Foundation and others.

2. Keywords

  • Acute Myocardial Infarction, ST-Elevation Myocardial Infarction (STEMI), Primary Percutaneous Coronary Intervention (PCI), Fibrinolysis, Thrombolysis, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with acute ST-elevation myocardial infarction (STEMI) presenting to hospitals without PCI capability (Population), does a strategy of immediate transfer for primary percutaneous coronary intervention (PCI) (Intervention) compared to on-site fibrinolytic therapy (Comparison) reduce the composite risk of death, reinfarction, or disabling stroke at 30 days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: At the time, both primary PCI (angioplasty) and intravenous fibrinolysis (“clot-busting” drugs) were established treatments for STEMI. Primary PCI was known to be more effective at restoring blood flow when performed quickly at a specialized center, but most patients presented to local hospitals without this capability.
  • Knowledge Gap: It was a major clinical and logistical question whether it was better to give immediate on-site fibrinolysis or to accept the time delay required to transfer a patient to a specialized PCI center. The potential benefit of the more effective reperfusion with PCI had to be weighed against the potential harm of a longer time to treatment.
  • Proposed Hypothesis: The authors hypothesized that a strategy of rapid transfer for primary PCI would be superior to on-site fibrinolysis in reducing the risk of death, reinfarction, or disabling stroke.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 24 referral hospitals (without PCI) and 5 invasive (PCI-capable) centers in Denmark.
  • Trial Period: Enrollment ran from December 1997 to December 2001.
  • Population:
    • Inclusion Criteria: Adult patients (no upper age limit) presenting within 12 hours of the onset of symptoms of an acute MI with ST-segment elevation.
    • Exclusion Criteria: Included contraindications to fibrinolysis and cardiogenic shock.
  • Intervention: Patients were immediately transferred to a designated PCI-capable center for primary angioplasty.
  • Control: Patients received on-site intravenous fibrinolytic therapy with alteplase.
  • Management Common to Both Groups: All patients received standard medical therapy for acute MI, including aspirin and heparin.
  • Power and Sample Size: The authors calculated that a sample size of 1560 patients would be required to have 80% power to detect a 4% absolute risk reduction in the primary outcome. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: A composite of death from any cause, clinical reinfarction, or disabling stroke within 30 days.
    • Secondary Outcomes: Included the individual components of the primary outcome and the composite of death or reinfarction.

6. Key Results

  • Enrollment and Baseline: 1572 patients were randomized (784 to PCI and 788 to fibrinolysis). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The primary composite outcome occurred in a significantly lower proportion of patients in the PCI group: 66 of 784 patients (8.5%) in the PCI group met the primary endpoint, compared with 109 of 788 patients (14.2%) in the fibrinolysis group (p=0.0003).
  • Secondary Outcomes: The risk of reinfarction was significantly lower in the PCI group (1.6% vs. 6.3%). There was a trend towards lower mortality in the PCI group (6.6% vs. 8.7%), but this was not statistically significant.
  • Adverse Events: The incidence of major adverse events was lower in the PCI group.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who met the composite endpoint between the two groups.
  • Key Statistic(s) Reported: Risk Ratio for the primary outcome: 0.60 (95% CI, 0.45 to 0.80; P-value: 0.0003).
  • Interpretation of Key Statistic(s):
    • Risk Ratio (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: The paper reports the result as 0.60.
      • Clinical Meaning: The RR of 0.60 means that patients in the PCI group had a 40% lower relative risk of death, reinfarction, or disabling stroke at 30 days compared to the fibrinolysis group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.45 to 0.80.
      • Clinical Meaning: Since this entire range is well below the line of no effect (1.0), it confirms that the result is highly statistically significant and demonstrates a clear benefit for the PCI strategy.
    • P-value: The p-value of 0.0003 is extremely low, indicating the result is highly statistically significant (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group)
      • Calculation: ARR = 14.2% – 8.5% = 5.7%.
      • Clinical Meaning: For every 100 patients managed with a transfer-for-PCI strategy, about 6 additional patients were saved from death, reinfarction, or disabling stroke.
    • Number Needed to Treat (NNT):
      • Formula: NNT = 1 / ARR
      • Calculation: NNT = 1 / 0.057 = 17.5, which is rounded down to 17.
      • Clinical Meaning: You would need to treat 17 patients with a transfer-for-PCI strategy to prevent one additional case of death, reinfarction, or disabling stroke.
  • Subgroup Analyses: The benefit of the PCI strategy was consistent across all pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The large, multicenter, randomized, controlled design provided high-quality evidence on a critical clinical and logistical question.
  • Generalizability: The pragmatic design, involving a network of community and tertiary hospitals, makes the findings highly generalizable to real-world healthcare systems.
  • Statistical Power: The study was large and adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome was a composite of the most important patient-centered outcomes in acute MI.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The trial was conducted in a well-organized healthcare system (Denmark) with relatively short transfer times (median of 32 minutes). The benefit of a transfer strategy might be less pronounced in systems with longer transfer delays.
  • Other: The fibrinolytic regimen used (alteplase) may not be representative of all lytic strategies.

10. Conclusion of the Authors

  • The authors concluded that interhospital transfer of patients with STEMI for primary PCI is superior to on-site fibrinolysis, provided the transfer can be accomplished rapidly.

11. To Summarize

  • Impact on Current Practice: This was a profoundly practice-changing trial. It provided the definitive evidence that established the “hub-and-spoke” model of regional STEMI care as the international standard. It demonstrated that it is better to “treat on the table” (in the cath lab) than “treat on the street” (with fibrinolytics).
  • Specific Recommendations:
    • Patient Selection: For adult patients with STEMI presenting to a hospital without PCI capability.
    • Actionable Intervention: A strategy of rapid transfer to a PCI-capable center should be the primary reperfusion strategy.
    • Expected Benefit: This strategy can be expected to prevent one additional death, reinfarction, or disabling stroke for every 17 patients treated.
  • What This Trial Does NOT Mean: This trial does NOT mean that fibrinolysis has no role. It remains an important option in settings where transfer times are prohibitively long.
  • Implementation Caveats: The success of this strategy is entirely dependent on having a well-organized, efficient system for rapid patient transfer and activation of the cardiac catheterization lab.

12. Context and Related Studies

  • Building on Previous Evidence: The DANAMI-2 trial (2003) was designed to provide a definitive answer to the “lytics vs. transfer” debate, which had been explored in several smaller, less conclusive trials.
  • Influence on Subsequent Research: The definitive positive result of this trial led to the widespread reorganization of acute cardiac care into regional STEMI networks around the world.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The trial did not define the maximum acceptable “door-to-balloon” time delay for a transfer strategy to remain superior to immediate fibrinolysis.
  • Future Directions: Subsequent research has focused on optimizing the logistics of STEMI systems of care and on adjunctive pharmacotherapies to improve outcomes in primary PCI.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a fundamental strategic decision in the management of a time-sensitive and life-threatening condition.
  • Methods: The large, multicenter, pragmatic RCT design was appropriate and robust. The main methodological weakness is the open-label design. However, the primary outcome was a composite of objective endpoints, which mitigates the risk of bias.
  • Results: The study reported a statistically significant and clinically important benefit for the transfer-for-PCI strategy (NNT of 17). The findings were consistent and robust.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable to any healthcare system that can organize efficient inter-hospital transfers. This is a classic example of a high-quality trial that was profoundly practice-changing by providing strong evidence to reorganize an entire system of care.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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