Trattamento trombolitico dell'ictus ischemico acuto

The enormous initial success of treating coronary thrombosis with thrombolytic therapy made the thrombolytic treatment of ischaemic stroke the obvious next step. Although coronary thrombolysis has now been superseded by primary angioplasty, thrombolysis is the standard of care for stroke if it can be done within 4.5 hours of the known onset of a stroke. ¹

How common is ischaemic stroke? (Epidemiology)²³⁴

• As of 2022, stroke was the fourth biggest single cause of death in England and Wales.

• There are around 100,000 strokes every year in the UK, with around 1.3 million people living with the consequences of stroke.

• Stroke incidence fell by 30% between 1999 and 2011, probably due to better management of cardiovascular risk factors in primary care.

• Sebbene l'incidenza aumenti con l'età, l'età media è diminuita di 1-2 anni tra il 2007 e il 2016, quando era di 68 anni per gli uomini e 73 per le donne. In Scozia, le età equivalenti sono rispettivamente 71 e 76.

• Non c'è limite di età per l'uso della terapia trombolitica.

It is essential to have a CT or MRI scan to differentiate the type of stroke before commencing treatment. The use of MRI as a first-line tool has the potential to reduce thrombolysis of stroke mimics, but this must not be at a cost of delay. Access to these investigations, and to staff trained to interpret them, must be immediately available 24 hours a day.

The important differential diagnoses are ictus emorragico, including intracranial haemorrhage and emorragia subaracnoidea, and attacco ischemico transitorio (TIA).

The 2023 National Clinical Guidelines for Stroke is endorsed by the National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and the Royal College of Physicians. NICE also have a separate guideline on stroke, updated in 2022.

Recommendations include the following:

• La trombolisi con alteplase - nota anche come attivatore tissutale del plasminogeno (tPA) - dovrebbe essere la trombolisi di scelta quando si considera la trombolisi. Il suo uso dovrebbe essere limitato alle seguenti circostanze:

  • Haemorrhagic stroke has been excluded.

  • Il paziente si presenta entro quattro ore e mezza dall'evento.

  • It is administered within a well-organised stroke service.

• Acute stroke services must link with the ambulance service; as well as being able to provide emergency care, they must also have facilities to deal with swallowing assessment, hydration and nutrition, palliative care, secondary prevention and rehabilitation. They must also provide education for all staff who give acute stroke care, including those in the emergency department.

• Ogni paziente trattato con alteplase dovrebbe iniziare un agente antipiastrinico entro 24 ore, salvo controindicazioni.

• I pazienti idonei per la trombectomia meccanica dovrebbero ricevere anche la trombolisi il prima possibile.

Nel 2023, solo il 10,7% dei pazienti che hanno un ictus viene trattato con trombolisi e il 3,1% con trombectomia. Questo rappresenta un leggero miglioramento rispetto al 10,4% e al 2,5% rispettivamente dell'anno precedente. Solo il 40% viene ammesso in un'unità ictus entro quattro ore e solo il 76,5% trascorre almeno il 90% del loro ricovero in un'unità ictus.

A new NICE guidance published in July 2024 authorised the use of a second thrombolytic agent, tenecteplase, on the same basis (for thrombolysis up to 4.5 hours after presentation, when intracranial haemorrhage has been excluded). The guidance says that the less expensive of the two agents should be used. ⁸

Absolute contraindications include a recent intracranial haemorrhage or structural cerebral vascular lesion or neoplasm, possible aortic dissection, active bleeding (excluding menstruation), recent intracranial or spinal surgery and current severe uncontrolled hypertension.

Relative contraindications include a history of severe and poorly controlled hypertension, prolonged cardiopulmonary resuscitation (over 10 minutes), major surgery in the last three weeks, dementia, pregnancy, non-compressible vascular punctures and an active peptic ulcer.

The most serious complication is intracranial haemorrhage - a 2023 systematic review gave the likelihood of this as 1.7 - 8.8%. Risk factors for intracranial haemorrhage include age, hypertension, atrial fibrillation and the use of antiplatelet or anticoagulant therapy; however, a haemorrhage can only be confirmed or excluded after appropriate imaging. The Stroke Association patient leaflet gives an intracranial haemorrhage rate of 4% within seven days of thrombolysis and advises that 2.5% of these will be fatal.

A 2018 study followed over 2000 patients who had received thrombolysis between 2005 and 2015. They found that the number needed to treat to prevent one death was 12 at five years and 20 at 10 years. Thrombolysis reduced mortality by 37% at 10 years (slightly more for those who arrived at hospital within three hours of symptom onset) and on average, by 10 years, treated patients had lived one year longer than controls. At five years, thrombolysis was associated with higher independence scores with an odds ratio of 3.76.

Ammissione rapida

Although the high technology of scanning and thrombolysis is delivered within a hospital system, there are still implications for primary care, the most obvious being that the speed of getting a patient to a thrombolysis unit is critical. A nationwide cohort study in Denmark found that symptom to thrombolysis time of over 90 minutes was associated with a higher risk of death or recurrent ischaemic stroke. ¹²

Even if the 4.5 hour cut-off for thrombolysis has passed, patients should still be admitted to hospital, as all should have a scan within 24 hours and the outcome for all is better in a stroke unit.

Gestione iniziale di TIA sospetta e confermata³⁷

• Offrire aspirina (300 mg al giorno), a meno che non sia controindicata, alle persone che hanno avuto un sospetto TIA, da iniziare immediatamente. Coloro che stanno già assumendo aspirina a basso dosaggio dovrebbero continuare con questa e non assumere una dose da 300 mg.

• Refer immediately people who have had a suspected TIA for specialist assessment and investigation, to be seen within 24 hours of onset of symptoms. If someone presents having had a suspected TIA more than seven days ago, they should be referred as soon as possible and definitely within another seven days.

• Non utilizzare sistemi di punteggio, come ABCD², per valutare il rischio di ictus successivo o per informare sull'urgenza del rinvio per le persone che hanno avuto un TIA sospetto o confermato.

• Offrire la prevenzione secondaria, oltre all'aspirina, il prima possibile dopo la conferma della diagnosi di TIA.

• Patients with a suspected TIA should not drive until they have seen a specialist, who will give definitive advice.

Prevenzione secondaria

This is discussed in the separate Prevenzione dell'ictus articolo.