Intracranial bleeding after tenecteplase rises with blood pressure, age and dose

Design

Pooled individual patient data from 6 randomised trials

Population

15,954 STEMI patients given weight-adjusted tenecteplase

Primary outcome

Intracranial haemorrhage

Effect

169 events; aOR 1.02 per mmHg systolic above 110 (95% CI 1.01-1.03); female aOR 1.49 (1.06-2.11)

Investigators pooled individual patient data from six randomised trials of weight-adjusted tenecteplase for STEMI (ASSENT-2, ASSENT-3, ASSENT-3 PLUS, ASSENT-4 PCI, STREAM and STREAM-2), all of which excluded pressures above 180/110 mmHg. Of 15,954 patients, 169 had an intracranial haemorrhage.

Above a systolic pressure of 110 mmHg, each additional 1 mmHg was linked to about 2% higher odds of haemorrhage, with a steep rise beyond 160 mmHg. Women had higher odds (adjusted OR 1.49) and so did lighter patients (OR 1.16 per 5 kg less). Age mattered more at higher doses: odds rose about 1% per year of age at 30 mg but nearly 7% per year at 50 mg. A model built from these factors discriminated reasonably well (C index 0.72).

In India, where fibrinolysis is still the first reperfusion for many STEMI patients, this is directly usable. Blood pressure at the moment of lysis and dose in the older patient are the two things a clinician can change. These are associations within trial populations, so the size of benefit from lowering pressure is not tested here.

• Measure systolic pressure immediately before tenecteplase; values above 160 mmHg carried a much higher risk.
• Consider lowering raised blood pressure promptly before giving lysis, without delaying reperfusion.
• In older patients, consider whether a reduced dose is appropriate, as used in later tenecteplase trials.
• Weigh the patient where possible rather than estimating; lighter patients had higher risk.
• Women and low-weight older patients are the group to discuss risk with most carefully.

Why it matters

Intracranial bleeding is the complication that makes clinicians hesitate over lysis, and its main drivers turn out to be adjustable at the bedside.

Don't overread it

These are associations; the analysis did not test whether lowering blood pressure before lysis prevents bleeding.

The statistics, in plain English

An odds ratio of 1.02 per mmHg sounds small, but it compounds: 40 mmHg higher means roughly double the odds. A C index of 0.72 means the model ranks a patient who bled above one who did not about 72% of the time, useful but far from certain. With only 169 events, the estimates for smaller groups are imprecise.

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