BACKGROUND AND AIMS: Intracranial haemorrhage (ICH) is a significant complication of fibrinolytic therapy for ST-elevation myocardial infarction (STEMI). The risk factors for ICH following tenecteplase (TNK) administration were evaluated, and a clinical risk prediction tool was developed.
METHODS: A pooled individual patient data analysis from STEMI patients who received weight-adjusted TNK with a consistent blood pressure exclusion criterion of >180/110 mmHg in six randomized controlled trials (ASSENT-2, ASSENT-3, ASSENT-3 PLUS, ASSENT-4 PCI, STREAM, STREAM-2) was undertaken. Logistic regression was used to model risk factors, and a nomogram was developed for individual risk prediction.
RESULTS: Among 15 954 patients, 169 developed ICH. Above a systolic blood pressure (SBP) threshold of 110 mmHg, each 1 mmHg increase conferred a 2% relative increase in ICH risk [adjusted odds ratio (aOR) 1.02, 95% confidence interval (CI) 1.01-1.03; P < .0001]; risk accelerated sharply beyond 160 mmHg. With increasing dose, the likelihood of ICH increased with age, rising from 1% per year (30 mg TNK) to nearly 7% per year with 50 mg. The multivariable model incorporating age, sex, SBP, body weight, and TNK dose with the age-dose interaction demonstrated good discrimination (C index 0.718; 95% CI 0.68-0.76). Female sex conferred a 49% increased ICH risk (aOR 1.49, 95% CI 1.06-2.11; P = .023), and each 5 kg decrease in body weight was associated with 16% increased odds of ICH (aOR 1.16, 95% CI 1.03-1.30; P = .014).
CONCLUSIONS: Dose reduction of TNK in older patients and SBP optimization before fibrinolytic administration represent modifiable strategies to potentially reduce ICH.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Cardiology |  |
Useful information to guide fibrinolytic therapy for STEMI in settings where primary PCI is not available.
This study evaluates a tool to help assess potential harms (intracranial hemorrhage/ICH) from TNK for STEMI. There were 168 ICH events among ~16k patients. The risk of symptomatic intracranial hemorrhage increased with age, blood pressure, weight, dose, and female sex. Fibrinolysis for STEMI is not a benign procedure. Immediately modifiable risk factors can be addressed, as can the dose. Getting informed consent is important when advising our patients. There's a tool for that; Figure 4 is a nomogram.
This is an interesting analysis looking at rates of ICH based on several variables. The increase in ICH rates based on BP in their model is especially interesting in the elderly, but their analysis did not evaluate the possible effectiveness of giving lower doses (even though ICH risk went down). This model will need to be tested to also include the effectiveness of lower dosing. However, using a lower threshold for BP in TNK in STEMI, especially in the elderly, should probably be revisited based on current recommendations.