Advances in the Modern Management of Ischaemic Stroke and Secondary Prevention

 In recent years breakthrough advances have occurred in the management of ischaemic stroke, greatly improving clinical outcomes. Along with the availability of clot retrieval for acute management of stroke there have been advances in stroke secondary prevention. The following article summarises the highlights of the talk given on the Modern Management of Stroke at the Nordoc conference in June 2019 and focuses on recent updates in the field.

Facts about stroke:

Stroke is one of Australia’s biggest killers and a leading cause of disability, killing more women than breast cancer and more men than prostate cancer (1). Even when patients survive, most suffer a disability that impedes their carrying out the activities of daily living unassisted (2). Therefore, it is of utmost importance to look for new ways and strategies to reduce the detrimental consequences of stoke.

Endovascular therapies:

One of the breakthrough advances has been the implementation of clot retrieval in the management of stroke caused by a large vessel occlusion. A series of clinical trials published in 2015 showed consistently that endovascular treatment, in combination with best practice medical treatment, was superior to the latter treatment alone for patients suffering acute occlusion of the internal carotid artery or the main stem of the proximal middle cerebral artery. The number needed to treat in most studies ranges between 3 to 7 to achieve a positive outcome and functional independence (3,4,5,6,7).

It is now standard clinical practice that all patients presenting with acute ischaemic stroke be urgently assessed and considered for endovascular therapy within 24 hours of symptom onset or last being seen well.  As life saving therapies are available it is important for GPs to recognise and educate patients on the urgency of action when stroke symptoms develop. 

Standard investigations for stroke:

It is routine practice to perform imaging of the brain during clinical investigations of stroke patients.

A non-contrast CT scan is used to exclude a haemorrhage, while CT angiography and CT perfusion are important to further assess the aetiology of stroke before any therapies are initiated. Subsequently, patients will also undergo an MRI of the brain to determine the extent of the stroke if no contraindications exist. Other routine investigations include carotid ultrasound, which looks for carotid artery stenosis, 24 hour holter or telemetry monitoring to look for atrial fibrillation, an echocardiogram used to exclude cardiac thrombus and screening for diabetes mellitus and hyperlipidaemia.

Stroke in younger patients and patent foramen ovale:

Although the risk of stroke increases with age, mostly related to atherosclerotic disease, we also see younger patients (60 years of age or younger) without traditional risk factors presenting with stroke. In this group the alternative causes of stroke such as thrombophilia or paradoxical embolism through a patent foramen ovale (PFO) need to be explored.

Several studies have demonstrated that in selected patients a PFO closure reduces the risk of stroke recurrence (8,9). This procedure is often beneficial in younger patients with stroke after thorough investigations were completed and alternative causes ruled out.

Standard medical therapy for secondary prevention in ischaemic stroke:

Antiplatelet therapy is an effective secondary prevention strategy in stroke patients without an identifiable cardioembolic cause and guidelines recommend aspirin within the first 48 hours of symptoms onset (10).

Direct oral anticoagulants (DOAC’s) are preferred to Warfarin for secondary management in patients with proven cardioembolic stroke. 

Blood pressure control is a very important modifiable risk factor for stroke. All stroke and TIA patients, with a clinic blood pressure of >140/90mmHg, should have long term blood pressure lowering therapy initiated or intensified. Preferred agents for blood pressure lowering therapy include angiotensin-converting-enzyme inhibitor, angiotensin II receptor antagonists, calcium channel blocker and or thiazide diuretics. Beta-blockers should not be used as first-line agents unless the patient has ischaemic heart disease (13). 

All patients with ischaemic stroke or TIA with a possible atherosclerotic component and who have a reasonable life expectancy should be prescribed a high-potency statin, regardless of baseline lipid levels. (14)

Is there a role for dual antiplatelet therapy (DAPT) in ischaemic stroke?

In special circumstances such as high-risk TIA and minor stroke, a short duration for 3 to 4 weeks of dual antiplatelet therapy has proven to be a safe and effective secondary prevention therapy. It is imperative that following this period DAPT is stepped down to a single antiplatelet agent for long term prevention, as the risk of bleeding increases with time and outweighs the benefit (11,12).

Conclusion

New advances in acute management of stroke, along with secondary prevention, have led to improved patient outcomes. It is of vital importance that health professionals keep up to date with those changes so that we can apply this knowledge in our clinical practice. The main message however remains the same:  time is brain and the education of patients on how to recognise symptoms of stroke and call urgently for an ambulance  is vital.

References:

1. Australian Institute of Health and Welfare 2018. Australia’s Health 2018
2. Deloitte Access Economics. The economic impact of stroke in Australia, 2013
3. Berkhemer OA, Fransen PSS, Beumer D, et al. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015;372:11-20
4. Jovin TG, Chamorro A, Cobo E, et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296-2306\
5. Goyal M, Demchuk AM, Menon BK, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372:1019-1030
6. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-1018
7. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015;372:2285-2295
8. Mas JL, Derumeaux G, Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med 2017;377:1011-1021
9. Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med 2017;377:1022-1032
10. Stroke Foundation. Clinical Guidelines for Stroke Management 2017. Melbourne: Stroke Foundation; 2017 [cited 2019 May 29]
11. Wang Y, Wang Y, Zhao X, Liu L, Wang D, Wang C et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013; 369: 11–9.
12. Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ et al. Clopidogrel and aspirin in acute ischemic stroke and high‐risk TIA. N Engl J Med 2018; 379: 215–25
13. Lakhan SE, Sapko MT: Blood pressure lowering treatment for preventing stroke recurrence: a systematic review and meta-analysis.. International archives of medicine 2009;2(1):30- Pubmed Journal
14. Kongnakorn T, Ward A, Roberts CS et al: Economic evaluation of atorvastatin for prevention of recurrent stroke based on the SPARCL trial. Value in health: the journal of the International Society for Pharmacoeconomics and Outcomes Research 2009;12(6):880-7- Pubmed Journal