PRAGUE 2 - PRAGUE 2

Description:

This was a randomized trial comparing on-site thrombolysis in community hospitals to transfer for primary angioplasty.

Hypothesis:

Transfer for primary percutaneous coronary intervention (PCI) would be superior to on-site thrombolysis in community hospitals.

Study Design

Patients Enrolled: 850 (421 thrombolysis vs. 429 PCI)
Mean Follow Up: 5 years
Mean Patient Age: Mean 64 years (thrombolysis), 65 years (PCI)

Patient Populations:

Acute ST-segment elevation MI <12 hours, and presentation to community hospital without catheterization facilities

Exclusions:

Femoral pulses not palpable bilaterally, contraindication to thrombolytic therapy, or failure to initiate transfer within 30 minutes

Secondary Endpoints:

1) Composite of mortality, reinfarction, or stroke at 30 days; 2) Stratification of outcome by presentation <3 hours; 3) Stratification of outcome by presentation 3-12 hours; and 4) 30-day mortality (treatment received)

Drug/Procedures Used:

Patients were randomized to transfer to a tertiary care center for primary PCI or thrombolytic therapy with streptokinase.

Concomitant Medications:

Aspirin (500 mg), unfractionated heparin followed by Fraxiparin for 3 days, and ticlopidine for 30 days in both arms

Principal Findings:

Thirty-day mortality was not different in an intention-to-treat analysis (10% thrombolysis vs. 6.8% PCI, p=0.12). While there was no mortality difference in patients presenting <3 hours, those presenting 3-12 hours from symptom onset showed benefit with PCI (15.3% thrombolysis vs. 6% PCI; p < 0.02). When analyzed by the treatment used, the 30-day mortality difference became statistically significant (10.4% thrombolysis vs. 6% PCI; p < 0.05).

Four patients randomized to transport for PCI developed shock prior to transfer and received thrombolysis. Three of these died within 24 hours. The incidence of adverse events was 1.2% during transport (two deaths and three ventricular fibrillatory arrests). Door-to-treatment times were 72 minutes in the thrombolysis group and 94 minutes in the PCI arm. Mean transport time was 48 minutes.

At 5-year follow-up, there was no difference in mortality (23.5% for thrombolysis vs. 20.7% for PCI, p = NS). Mortality from 30 days to 5 years was identical in both groups at 15% each. The composite of death, MI, or stroke at 5 years was lower in the PCI group compared with the thrombolytic group (36.5% vs. 43.3%, p = 0.0417).

Interpretation:

Among patients with ST elevation myocardial infarction (MI), routine transfer for PCI was associated with a reduction in the composite of death, MI, or stroke compared with thrombolytic therapy. Routine administration of glycoprotein IIb/IIIa receptor antagonist prior to planned PCI for acute MI was not employed and may confer additional benefit in transfer patients. One drawback to the study is the fact that newer fibrinolytic agents were not used.

The rates of rescue angioplasty were not reported, which if used in conjunction with thrombolytic agents, may improve outcomes. At late 5-year follow-up, there was no difference in mortality, but the reduction in the composite of death, MI, or stroke with PCI was maintained.

It is likely that the rapid transfer and door-to-balloon times (90 minutes) seen in this trial cannot be replicated in the community setting (198 minutes in the US NRMI 4 experience) and may reduce the benefit of transfer for PCI during acute MI. The incremental increase in benefit for PCI in patients presenting later in the course of acute MI (3-12 hours), remains to be validated in randomized trials stratified based on time to presentation.

References:

Widimský P, Budesínský T, Vorác D, et al. Long distance transport for primary angioplasty vs immediate thrombolysis in acute myocardial infarction. Final results of the randomized national multicentre trial--PRAGUE-2. Eur Heart J. 2003 Jan;24(1):94-104.

Long-term follow-up data presented by P. Widimsky, European Society of Cardiology Scientific Congress, September 2006.

Presented by P. Widimsky at the Annual Meeting of the European Society of Cardiology, August 31, 2002.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Thrombolytic Therapy, Myocardial Infarction, Stroke, Follow-Up Studies, Streptokinase, Catheterization, Fibrinolytic Agents, Angioplasty, Stents, Percutaneous Coronary Intervention, Platelet Glycoprotein GPIIb-IIIa Complex


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