Management Of Stroke Health Article

Lifestyle changes: many stroke patients benefit from lifestyle changes including cessation of smoking, weight reduction and modification of excess alcohol intake.

Blood pressure lowering: the PROGRESS trial showed that blood pressure reduction (using perindopril and indapamide) after haemorrhagic or ischaemic stroke reduces the risk of subsequent stroke even in patients with ‘normal’ blood pressure. ⁴ However, blood pressure should not be reduced aggressively in those with bilateral severe carotid stenosis, and possibly in severe basilar or bilateral vertebral artery disease, because this may increase the risk of stroke by compromising cerebral blood flow.

Cholesterol lowering: the Heart Protection Study showed that treatment with simvastatin, 40 mg, reduces the risk of stroke and other vascular events in high-risk patients (previous ischaemic stroke, coronary or peripheral vascular disease or diabetes). ⁵ This was the case even in patients with ‘normal’ cholesterol levels (low-density lipoprotein cholesterol <3.5 mmol/litre). In the subgroup of patients with pre-existing cerebrovascular disease, treatment with simvastatin reduced major vascular events by 20% over the 5-year treatment period. Notably, there was no increased risk of haemorrhagic stroke, contradicting previous suggestions that cholesterol reduction is associated with such a risk. Because patients with primary intracerebral haemorrhage are at high risk of further thrombotic vascular events, it could be argued that they should also receive statins.

Antiplatelet agents reduce the risk of recurrent stroke and vascular death; treatment of 1000 patients for 3 years after stroke results in 36 fewer serious vascular events and 15 fewer deaths per 1000 patients. Most trial data concern aspirin, but newer antiplatelet agents such as clopidigrel and extended-release dipyridamole are also effective. However, it is uncertain whether they provide sufficient additional benefit over aspirin to justify the extra cost.

There is interest in combination antiplatelet therapy, particularly in patients perceived to be at high risk of recurrent ischaemic events. The ESPS 2 trial showed a relative risk reduction for stroke of 30% (9.5% vs 12.5%) with aspirin and dypiridamole vs aspirin alone in patients with prior TIA or ischaemic stroke. Similar results were shown by the more recent ESPRIT trial. ⁶ In contrast, the MATCH trial ⁷ of clopidogrel and aspirin vs clopidogrel alone showed no additional benefit with the combination therapy. There are several other ongoing trials of combination therapy.

Anticoagulation has been considered for secondary prevention of stroke in patients in sinus rhythm.

• A recent trial of aspirin vs warfarin in patients in sinus rhythm (WARSS), in which subjects were not selected according to stroke aetiology (but those with cardioembolic sources or > 50% carotid stenosis were excluded), showed no additional benefit with warfarin at a mean INR of 1.8 (target INR 1.4–2.8).

• Treatment with warfarin to a target INR of 3–4.5 (SPIRIT trial) has been shown to be associated with significant harm caused by an increase in major bleeding complications, particularly intra-cerebral haemorrhage.

• The ongoing anticoagulation arm of the ESPRIT trial is comparing aspirin, aspirin and extended-release dipyridamole, and warfarin (INR 2–3).

Patients who have suffered a stroke and are in atrial fibrillation are at high risk and should be anticoagulated if there are no contraindications. Because of the lack of randomized evidence, patients with presumed cardioembolic stroke secondary to other causes should receive antithrombotic therapy on an individual basis. No significant difference between anticoagulants and aspirin was found in a recent study of stroke secondary to patent foramen ovale.

Surgical/endovascular treatments: significant atherosclerotic narrowing at or around the origin of the ipsilateral internal carotid artery is found in about 20–30% of patients with TIAs or ischaemic stroke. Combined data from the three major randomized trials of endarterectomy for symptomatic carotid stenosis showed that surgery was highly beneficial in those with a stenosis of 70% or more and moderately beneficial for 50–69% stenosis ( Figure5). However, there was no clear benefit in patients with the most severe disease (near-occlusion). Operative mortality was 1.1% and the operative risk of stroke and death was 7.0%.

Several other clinical and angiographic characteristics influence the efficacy of surgery, particularly the timing ( Figure 6). ⁸ With the recent suggestion that the risk of early recurrent stroke is very high in large artery-associated stroke (see below), and evidence from endarterectomy trials that the benefit of surgery is greatest in the first few weeks after stroke, early surgery is becoming more common. Early carotid surgery (<3–6 weeks after symptom onset) appears not to carry an increased risk of complications compared with surgery performed later, in patients who are clinically stable.

Carotid angioplasty is currently being evaluated as an alternative to endarterectomy. Current evidence from the CAVATAS investigators suggests that angioplasty with or without stenting is associated with a procedural risk similar to that of endarterectomy, but a higher rate of re-stenosis during follow-up. However, improvements in cerebral protection devices may reduce the procedural risks, and several randomized trials of angioplasty and stenting with cerebral protection vs endarterectomy are ongoing.

Randomized controlled trials have not been performed in surgery or angioplasty for posterior circulation disease or intracranial disease. Such procedures are occasionally undertaken in patients whose symptoms persist despite antithrombotic therapy.

There is an increased incidence of patent foramen ovale (PFO) in patients with cryptogenic stroke but the risk of recurrent stroke is low and routine closure of PFO cannot as yet be recommended. The combination of atrial septal aneurysm and PFO was thought to carry a particularly high stroke risk but more recent data suggest that this is not the case.

Primary intracerebral haemorrhage: the PROGRESS trial included patients with primary intracerebral haemorrhage, and blood pressure lowering was seen to be beneficial (see above) in the prevention of recurrent stroke. In view of the increased vascular risk, such patients should probably also receive statins. Long-term treatment with aspirin is advocated by some authorities, to reduce the overall vascular risk. However, it is currently unclear how to predict those at high risk of recurrent hameorrhage and thereby determine the risk:benefit ratio in individual patients.