EBQ:A Comparison of Coronary Angioplasty with Fibrinolytic Therapy in Acute Myocardial Infarction

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Under Review Journal Club Article
Andersen H. "A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction". NEJM. 2003. 349(8):733-42.
PubMed Full text PDF

Clinical Question

In hospitals without PCA is transfer to centers with PCA superior to on site fibrinolytic therapy for STEMI?

Conclusion

Transfer of patients to treatment centers with PCA for reperfusion is superior to fibrinolytic therapy, given that the transfer take 2 hours or less.

Major Points

  • The composite endpoint favors angioplasty over fibrinolysis. Both referral centers and invasive centers show significant decrease in composite endpoints of the angioplasty group.
    • The decrease in composite endpoint is mainly driven by a decrease in re-infarction rates. Re-infarction is associated with a significant increase in 30 day mortality.
  • Enrollment in the study was stopped after a third interim analysis that showed angioplasty was favorable to fibrinolysis in referral center subgroup
  • Most patient's received intervention 2 hours after randomization, including referral center group
    • Ability for quick intervention
    • Likely similar to Western countries

Study Design

  • Cohort study of Danish patients with MI: Angioplasty vs. Fibrinolysis
    • Subgroup analysis
      • 24 referral hospitals without PCA capability
      • 5 intervention centers with PCA capability

Population

  • N= 1572
    • Referral hospitals
      • Fibrinolysis N=562
        • Median time of onset of symptoms to treatment: 169 min
      • Angioplasty N=567
        • Median time of onset of symptoms to treatment: 224 min
    • Invasive centers
      • Fibrinolysis N=220
        • Median time of onset of symptoms to treatment: 160 min
      • Angioplasty N=223
        • Median time of onset of symptoms to treatment: 188 min

Patient Demographics

  • Demographics such as age, sex, comorbidities, and medications were analyzed.
    • No statistical difference between groups
  • Angiographic features were recorded but not analyzed between referral and invasive centers

Inclusion Criteria

  • Age 18 yrs or older
  • Symptoms for 30 min to 12 hrs
  • ST segment elevation of 4 mm in at least 2 contiguous leads

Exclusion Criteria

  • Contraindication to fibrinolysis
  • LBBB
  • Acute MI and fibrinolytic treatment within previous 30 days
  • Pulseless femoral arteries
  • Previous coronary bypass surgery
  • Serum CR >2.83
  • Use of metformin
  • Non-ischemic heart disease
  • Life expectancy <1 yr due to non-cardiac causes
  • High risk during transportation
    • Cardiogenic shock/severe CHF (sustained SBP<65)
    • Persistent life threatening arrhythmia
    • Mechanical ventilation

Interventions

  • Fibrinolysis
    • 300 mg ASA PO
    • IV BB
    • TPA (Ateplase)
      • bolus 15 mg
      • 0.75 mg/kg over 30 min followed by 0.5 mg/kg over 60 min
    • Unfractionated heparin
      • bolus 5000U
      • 48 hr infusion to maintain PTT 70-90 sec
  • Angioplasty
    • 300 mg ASA IV
    • IV BB (same as fibrinolytic group)
    • Unfractionated heparin 10,000 U
      • Additional heparin to achieve a goal activated clotting time of 350-450 sec
    • IIb/IIIa blockers at discretion of physician
    • Stenting
      • Total occlusion, 30% stenosis culprit lesion, or <TIMI 3 flow
      • Vessels <2mm diameter excluded
    • Ticlopidine or Clopidogrel x 1 month post stenting
  • Failure: No resolution of or recurrent ST elevation
    • Repeat fibrinolysis prior to rescue angioplasty (fibrinolysis group)
    • Repeat angioplasty (angioplasty group)

Outcomes

  • Analysis with intention to treat principle

Primary Outcome

  • Composite endpoint of death, clinical re-infarction, or disabling stroke at 30 days
  • Death
    • All hosptials
      • Fibrinolysis: 7.8%
      • Angioplasty: 6.6%
p value = 0.35
  • Re-infarction
    • All hosptials
      • Fibrinolysis: 6.3%
      • Angioplasty: 1.6%
p value = <0.001
  • Disabling Stroke
    • All hosptials
      • Fibrinolysis: 2.0%
      • Angioplasty: 1.1%
p value = 0.15
  • Compositie Endpoint
    • All hosptials
      • Fibrinolysis: 13.7%
      • Angioplasty: 8.0%
p value = <0.001

Secondary Outcomes

Subgroup analysis

  • Death
    • Referral hospitals
      • Fibrinolysis: 8.5%
      • Angioplasty: 6.5%
p value = 0.20
    • Invasive centers
      • Fibrinolysis: 5.9%
      • Angioplasty: 6.7%
p value = 0.72
  • Re-infarction
    • Referral hospitals
      • Fibrinolysis: 6.2%
      • Angioplasty: 1.9%
p value = <0.001
    • Invasive centers
      • Fibrinolysis: 6.4%
      • Angioplasty: 0.9%
p value = 0.002
  • Composite Endpoint
    • Referral hospitals
      • Fibrinolysis: 14.2%
      • Angioplasty: 8.5%
p value = 0.02
    • Invasive centers
      • Fibrinolysis: 12.3%
      • Angioplasty: 6.7%
p value = 0.05

Criticisms & Further Discussion

  • 3 out of 5 intervention centers did not offer PCA as routine treatment prior to implementation of the study
  • Significance of composite endpoint decrease and therefor favorability of angioplasty was driven by re-infarction rates
    • There was no significant difference in the rate of death or disabling stroke at 30 days
  • Timing of onset of symptoms to various endpoints are noted. However, it is unclear how timing effects the endpoints. The author comments that most patients have a time of <2 hours from randomization to treatment.
    • It is unclear where "randomization" falls into the typical patient visit.
    • The suggested threshold of <2 hours is unclear
    • There is no mention of meaningfulness of symptom onset

Funding

Danish Heart Foundation, the Danish Medical Research Council, AstraZeneca, Bristol-Myers Squibb, Cordis, Pfizer, Pharmacia–Upjohn, Boehringer Ingelheim, and Guerbet.

References