Safety of off-label stroke treatment with tissue plasminogen activator

Many patients with acute ischaemic stroke do not receive intravenous thrombolysis due to contraindications. We aimed to assess safety, short-term clinical development, short-term outcome and mortality in patients treated off-label with tissue plasminogen activator (tPA).

Stroke patients treated with tPA within 4.5 h after symptom onset during 2006-2011 were prospectively included. Patients with contraindications to tPA according to national guidelines were compared to patients without any of these contraindications. Separate analyses were performed on patients who had compatible contraindications and did not receive tPA. Primary outcome was rate of symptomatic intracerebral haemorrhage (SICH). Secondary outcomes were short-term clinical development, short-term outcome and 30-day mortality.

Of the 265 patients who received tPA, 135 patients (50.9%) had formal contraindications and 130 patients (49.1%) had no such contraindications. Rates of SICH were similar for patients with or without contraindications (P = 0.305). Patients with contraindications to tPA had a similar rate of clinical improvement (P = 0.504), a trend of less favourable outcome (P = 0.052) and higher mortality (P = 0.005) than patients without contraindications. Logistic regression analysis showed no association between presence of contraindications to tPA and short-term outcome or mortality when adjusted for age, sex and admission National Institute of Health Stroke Scale score. Short-term outcome and mortality were similar in patients with contraindications who received tPA and patients with contraindications who did not receive tPA (n = 134).

Intravenous thrombolysis with tPA may be safe and efficient in stroke patients with a number of formal contraindications to tPA. Prospective randomized trials are imperative to clarify the need for a re-evaluation of the current contraindications to tPA.