Q. The following factors need to be considered when deciding whether or not to treat with alteplase. Which of the following factors are important?
- Patient’s age: True – RCTs of hyperacute treatments have excluded those under 16 years and many excluded patients over 80 yrs old. – Greater age is not associated with smaller treatment effects for thrombolysis however, it is associated with worse outcomes, and higher rates of complications with thrombolysis and thrombectomy, so it does need to be factored into decision making.
- Patient’s gender: False – There is no clear evidence from the literature that the patients’ sex makes a significant difference to the balance of benefits and risks. Of course, women on average present with stroke at an older age which is associated with worse outcomes:
- Delay since stroke onset: True – Shorter delays are associated with greater benefit for both:
- Thrombolysis
- Thrombectomy
However, it is clear that different individuals develop irreversible cerebral damage due to ischaemia at different rates, so that even beyond the usual treatment windows for thrombolysis (4.5 hours) and thrombectomy (6 hours) imaging markers can be used to identify some patients who benefit from later reperfusion.
See results of some relevant RCTs:
- Renal function: True – After adjustment for confounders in a meta-analysis, moderate (eGFR 30-59mL/min) to severe CKD eGFR 15-29mL/min) was associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.
However, renal impairment alone does not preclude treatment with thrombolysis or thrombectomy. - Blood pressure: True –
- RCTs of thrombolysis have excluded patients with very high blood pressure because of perceived increased risk of haemorrhage. Because of this the European licence excludes those with very high blood pressure and the the AHA recommend that Systolic BP should be <185mmHg and Diastolic BP <110mmHg before treatment.
- There is no reliable evidence to tell us whether patients with higher blood pressures do, or don’t benefit from thrombolysis
- The Enchanted trial showed that more intensive blood pressure lowering to target of 130-140mmHg rather than <180mmHg) was safe, reduced the risk of intracerebral bleeding but did not improve functional outcomes.
- Very high blood pressure would not be regarded as a definite reason to avoid thrombectomy (assuming thrombolysis was not being given as well) although the RCTs demonstrating that thrombectomy was effective did exclude those with blood pressures which were above the range thought to be safe for thrombolysis.
- Blood sugar: True –
- Hypoglycaemia might account for the neurological deficits, in which case thrombolysis would not be expected to have any benefit
- Observational studies have shown an association between high blood sugars (>22mmol/l) and poorer outcome but not necessarily any increased risk of bleeding after alteplase.
- There is no robust evidence that intensive treatment of hyperglycaemia in acute ischaemic stroke improves patients outcomes – over 60% of the patients in the SHINE trial had received thrombolysis.
- Presence of visual field defect: False – There is no evidence that patients with specific neurological deficits derive more or less benefit from thrombolysis.
However, given that reperfusion treatments are assumed to increase the likelihood of neurological deficits resolving, then patients with those deficits which create more problems for their everyday life might be perceived as benefitting more from treatment. Thus a patient may accept a greater risk of treatment to achieve resolution of a specific deficit. In this example if a visual field defect would prevent reading and/or driving then this might be seen as a stronger reason to treat. - Stroke severity: True –
- Stroke severity may be reflected by a high NIHSS scale or extensive changes on brain imaging
- Patients with very mild symptoms, or symptoms which would if they persisted, not impact on their lives may not accept even a small risk of potentially catastrophic adverse effects.
- Patients with more severe stroke may be perceived as having more to gain from treatment
- The risks of adverse outcomes including intracerebral bleeding are greater with more severe strokes but the effect of thrombolysis is similar despite this.
- Certainty of diagnosis: True –
- Patients whose neurological symptoms are not due to ischaemic stroke are unlikely to benefit from reperfusion therapies.
- Reperfusion is most likely to be effective if an artery is blocked by a thrombus.
- Strokes in which no artery is blocked by thrombus are unlikely to benefit.
- Some stroke mimics are likely to be associated with low risks of bleeding e.g. migraine, functional.
- Some stroke mimics and ischaemic lesions may be associated with high risks of bleeding e.g. encephalitis, vasculitis, dissection, post SAH delayed ischaemia.
- Atrial fibrillation: False – Whilst occluding thrombus derived from the left atrium may have different characteristics from that occurring in situ there are no reliable data to suggest that the balance of benefits and risks differs in patients with atrial fibrillation and sinus rhythm.
Strokes associated with atrial fibrillation tend to be more severe than those in patients with sinus rhythm and of course they may be on oral anticoagulants which are perceived to be a reason to avoid thrombolysis. - Perceived risks of bleeding: True – Many conditions are likely to be associated with a greater risk of bleeding with alteplase but quantifying the increased risk is difficult.
The following are perceived to increase the risk of bleeding:- Recent ischaemic strokes – unclear how recent?
- Previous ischaemic stroke and diabetes
- Previous intracranial bleed
- Severe stroke – based on NIHSS or brain imaging
- Warfarin with INR>1.6, or other oral anticoagulants or treatment dose heparin
- Low platelet count (<100,000/mm3)
- Recent trauma or surgery – but how recent?
- Known bleeding lesion e.g. duodenal ulcer
- Iron deficiency anaemia due to blood loss
- Organisational issues: True – The risks of treatment are perceived as less in well organised, well staffed settings where the staff are trained in giving treatment and monitoring the patient.
There may be a trade-off because it may take longer to get to the ideal setting which will reduce the benefits of reperfusion. However, once in the setting delays may be reduced. - The patient’s perspective: True – This is very important, but in hyperacute stroke can be difficult to elicit because of time constraints, communication difficulties and sometimes the need to rely on relatives or friends for information.
The presence and severity of cognitive impairment and/or existing disability will influence decision making.
The value a patient puts on possible resolution of a particular deficit and resulting disability is likely to influence their view of the balance of benefit and risks.
