Secondary prevention of stroke

Stroke is a common condition affecting approximately 150,000 people every year in the UK.

Risk factors include hypertension, diabetes mellitus, dyslipidaemia, cardiac disease, obesity, cigarette smoking and alcohol misuse.

The risk of recurrent stroke after a TIA or stroke is substantial, ranging from 35-43% over a five-year period. Secondary prevention strategies need to be implemented as soon as possible and continued throughout rehabilitation and recovery. Such measures need to be personalised and comprehensive.

Risk stratification
The risk of stroke after a TIA or minor stroke can be stratified using the ABCD2 scoring system (see box).

The two-day stroke risk is 1% for an ABCD2 score of 0-3, 4% for a score of 4-5 and 8% for a score of 6-7.

TIAs with an ABCD2 score ?4 are classified as high risk and guidelines advise urgent referral for specialist assessment and investigations within 24 hours.

Low-risk patients with an ABCD2 score <4 should have specialist assessment within one week.

Lifestyle modification
Although there is no RCT evidence that important lifestyle measures (tailored exercise, low-salt diet, smoking cessation and reduced alcohol intake) are effective in secondary prevention for stroke, it appears such measures may be important in reducing causal risk factors such as hypertension, hypercholesterolaemia and diabetes.

Lifestyle modification, consisting of weight loss, increased physical activity and a diet including at least five portions of fruit and vegetables per day, two portions of fish per week and reduced saturated fat, is suggested for all patients.

Hypertension
Hypertension is the most important treatable and causal risk factor for stroke. A meta-analysis of individual data for one million adults demonstrated that throughout middle and old age, usual BP is strongly and directly related to stroke-related mortality, without any evidence of a threshold down to at least 115/75mmHg.

More specifically, at 40-69 years, each difference of 20mmHg usual systolic BP (or, approximately equivalently, 10mmHg usual diastolic BP) was associated with a greater than twofold difference in the stroke death rate.

There is strong evidence that reduction in BP after stroke lowers the risk of subsequent vascular events. The PROGRESS study demonstrated that the addition of two BP-lowering agents (indapamide and perindopril) in patients with TIA or stroke (mean BP at entry 136/79mmHg) reduced BP by 12/5mmHg, which resulted in relative reduction of recurrent stroke by 42% over four years.

Current guidelines for BP control for secondary prevention of stroke advocate an optimal target BP of 130/80mmHg unless a patient has bilateral severe carotid artery stenosis, in which case, a slightly higher systolic BP target of 150mmHg is recommended.

BP lowering should be initiated for secondary prevention after the acute phase (before hospital discharge or at two weeks) because lowering BP earlier could reduce cerebral perfusion and lead to a worse outcome.

For patients aged ?55 years and African or Caribbean patients of any age, long-acting calcium-channel blockers or thiazide diuretics should be first line. If target BPs are not achieved, ACE inhibitors or ARBs should be considered. For patients aged <55 years, ACE inhibitors or ARBs should be considered as first-line treatments.

Lipid-lowering therapy
The Stroke Prevention with Aggressive Reduction of Cholesterol Levels (SPARCL) trial is the only published study investigating the efficacy of statin therapy in the secondary prevention of stroke or TIA in patients with no past history of coronary events.

It demonstrated that atorvastatin 80mg once a day caused an RR reduction of stroke by 15% over five years. These results have led to current guidelines advocating that all patients with a total cholesterol >4.0mmol/L or LDL cholesterol >2.0mmol/L who have had an ischaemic stroke or TIA should be treated with a statin unless contraindicated.

Guidelines advise that treatments with statins should be avoided or used with caution in patients with intracerebral haemorrhage.

Antiplatelet therapy
RCTs involving tens of thousands of patients worldwide have demonstrated the beneficial effect of aspirin in secondary prevention of ischaemic stroke.

Giving aspirin to patients who have had an ischaemic stroke in doses above 75mg daily reduces the risk of stroke by about 13%.

Dipyridamole and clopidogrel are two other antiplatelet agents used for stroke prevention and trials have demonstrated that a combination of aspirin and dipyridamole and clopidogrel alone are equally effective, but superior to aspirin alone.

However, the superior tolerability of clopidgrel alone and its cost, compared to aspirin and dipyridamole, have made clopidogrel the most cost-effective first-line antiplatelet therapy.

The combination of aspirin with dipyridamole may be used for patients who have had a stroke but are intolerant of clopidogrel, or in whom clopidogrel is contraindicated. Clopidogrel has no licence for use in patients with TIA; NICE guidelines recommend that dual aspirin and dipyridamole should be used first line.

Long-term combination of aspirin and clopidogrel is not recommended for long-term prevention unless there are specific cardiac indications.

Nerve block before endarterectomy: surgery reduces the absolute five-year risk of stroke (Photo: Dr P Marazzi/SPL)

Anticoagulation
There is evidence of the superiority of anticoagulation with warfarin compared with aspirin in the prevention of stroke in patients with AF approximating a two-thirds risk reduction.

Anticoagulation may be started immediately after a TIA or minor non-disabling stroke, but is recommended to commence at two weeks after acute cardio-embolic stroke to reduce the risk of haemorrhagic transformation.

To facilitate antithrombotic management decisions for the prevention of cardioembolic stroke associated with non-valvular AF, practical guidelines have been developed based on perceived stroke risk. A simple guide is based on the CHADS2-VASc scoring system.

For patients in whom anticoagulation with warfarin is contraindicated owing to poor compliance, alternative agents must be sought, which may include direct thrombin inhibitors, factor Xa inhibitors or left atrial appendage occlusion devices. Antiplatelets are not considered a suitable alternative where bleeding risks are high.

Carotid artery stenosis
Pooled data of carotid endarterectomy trials demonstrate that surgery reduces the five-year absolute risk of stroke by 16% in patients with 70-99% stenosis and by 4.6% in those with 50-69% stenosis.

Patients with carotid territory TIA or stroke without severe disability should be considered for carotid endarterectomy within one week of symptoms if they are neurologically stable and fit for surgery.

Carotid angioplasty or stenting have been developed as alternatives to surgery for symptomatic patients, although stroke risk is increased with stenting.

The risk of stroke in patients with asymptomatic carotid stenosis is very small, approximating to 1% per year, so carotid surgery for these patients is not warranted on a routine basis.

Treating unusual causes

In approximately 25% of stroke patients, younger patients in particular, no obvious cause of stroke is found and more extensive investigations are required to exclude associated factors, such as cervical dissection, intracranial disease, prothrombotic states and patent foramen ovale.

• Dr Bhalla is a consultant stroke physician at St Thomas' Hospital, London