PRAGUE-26 randomised 558 haemodynamically stable patients with acute pulmonary embolism, right ventricular dysfunction and a raised troponin or natriuretic peptide, to catheter-directed alteplase plus anticoagulation or anticoagulation alone. The primary outcome was a seven-day composite of death from any cause, recurrent embolism, or cardiorespiratory decompensation or collapse.
The composite occurred in 2 of 280 patients given thrombolysis (0.7%) and 19 of 278 given anticoagulation alone (6.8%), a relative risk of 0.10 with a confidence interval from 0.02 to 0.44. The authors attribute the difference mainly to fewer episodes of decompensation rather than to fewer deaths. One thrombolysis patient died within 30 days; four control patients died within seven.
Bleeding is where this needs care. Clinically relevant bleeding was 4.6% versus 5.0% and major bleeding 1.4% versus 2.2%, neither different. But intracranial haemorrhage occurred in two thrombolysis patients and none in the control arm. Two events cannot establish a rate, and they cannot be dismissed either: intracranial haemorrhage is the complication that makes systemic thrombolysis a decision rather than a protocol, and a catheter-directed route reduces that risk without abolishing it.
- Applies to intermediate-high risk: stable, with RV dysfunction and a raised biomarker
- The benefit is mostly avoided decompensation, not avoided death
- Two intracranial haemorrhages in the thrombolysis arm against none in control
- Open-label, and decompensation is a partly clinician-judged endpoint
- Requires a service that can deliver catheter-directed lysis promptly, which many cannot
The statistics, in plain English
A relative risk of 0.10 with an interval of 0.02 to 0.44 is a large effect that is clearly real, but the interval is wide because there were only 21 events in total. With counts that small the direction is secure and the magnitude is not: the truth could be a 98% reduction or a 56% one. The two intracranial haemorrhages are the reverse problem — too few events to estimate a rate, too serious to ignore.
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