- Design
- pooled individual patient data analysis of six randomised trials with a risk nomogram
- Population
- 15,954 patients with ST-elevation myocardial infarction given weight-adjusted tenecteplase
- Primary outcome
- intracranial haemorrhage after fibrinolysis
- Effect
- 169 events; 2% higher risk per mmHg systolic above 110 (aOR 1.02, 95% CI 1.01-1.03); age effect 1% per year at 30 mg vs nearly 7% at 50 mg
Individual patient data from six tenecteplase trials - ASSENT-2, ASSENT-3, ASSENT-3 PLUS, ASSENT-4 PCI, STREAM and STREAM-2, all sharing the same exclusion above 180/110 mmHg - were pooled to model intracranial haemorrhage. Among 15,954 patients, 169 bled intracranially.
Two modifiable inputs came out. Above a systolic of 110 mmHg, each additional 1 mmHg carried a 2% relative increase in risk (adjusted OR 1.02, 95% CI 1.01-1.03), with the curve steepening sharply beyond 160 mmHg. And the effect of age depended on dose: risk rose about 1% per year of age at the 30 mg dose, but nearly 7% per year at 50 mg. Two non-modifiable factors added to the model: female sex (adjusted OR 1.49, 95% CI 1.06-2.11) and lower body weight, each 5 kg less carrying 16% higher odds (adjusted OR 1.16, 95% CI 1.03-1.30). Discrimination was moderate, C index 0.718 (95% CI 0.68-0.76).
This matters most where fibrinolysis is still the usual reperfusion strategy, which includes much of India outside the large cities. It suggests that in an older, lighter patient the sequence before the bolus - optimise the systolic, then check the weight-band dose - is not routine box-ticking but the main lever on the complication that everyone fears. The authors frame dose reduction in older patients as a strategy to evaluate; it is not yet a licensed change to the dosing schedule.
- Optimise systolic pressure before the bolus, not after - risk climbs steeply above 160 mmHg.
- Recheck the weight band in older and lighter patients; the age effect is largest at 50 mg.
- Women had about 50% higher odds of intracranial bleeding after adjustment.
- A C index of 0.718 means the tool ranks risk usefully but does not identify individuals reliably.
- Dose reduction by age is a proposal from these data, not a licensed dosing change.
Why it matters
It reframes the pre-lysis pause from a checklist item into the main thing standing between an older patient and an intracranial bleed.
Don't overread it
A post hoc pooled analysis, not a trial of dose reduction - it cannot show that a lower dose in older patients is safe overall.
The statistics, in plain English
These are adjusted odds ratios from an observational analysis of pooled trial data, so they describe who bled rather than proving that changing the dose prevents bleeding. With 169 events in 15,954 patients the absolute risk is low, and a 49% relative increase for women is a small absolute one. The confidence interval for sex runs from 1.06 to 2.11, close enough to 1.0 at the lower end that the size of the effect is uncertain even though its direction is not.
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