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Stroke-Risk Reduction in AF
1. Overview and epidemiology of stroke
2. Costs of stroke
3. Consequences of stroke
4. AF a major risk factor for stroke
5. Medical management of stroke

1. Overview and epidemiology of stroke

A stroke occurs when the blood supply to part of the brain is interrupted causing damage to, or death of, brain cells deprived of oxygen and nutrients.

Because the brain controls the central nervous system and regulates virtually all human activity, damage to it can be devastating. Stroke causes a greater range of disabilities than any other condition1. Depending on which area of the brain is affected, a stroke can cause paralysis resulting in the loss of sensation and movement, as well as loss of memory, cognitive ability, emotion, speech, and the ability to swallow2. A third of all strokes are fatal2.

There are two main types of stroke:
puce Ischaemici – when a clot suddenly blocks an artery leading to, or within, the brain. The majority of strokes, 88 percent, are ischaemic, of which there are two types: thrombotici and embolici3.
puce Haemorrhagic – when an artery ruptures and bleeds into the brain tissue4.

 


Nearly half of all strokes are thrombotic. They occur when a blood clot forms within the cerebral artery and blocks blood flow. In an embolic stroke, the clot that blokes the cerebral artery has travelled as an embolus from elsewhere in the body, usually the heart3. Around a third of ischaemic strokes result from emboli originating in the heart. Most of those emboli are a result of artial fibrillation (AF). This proportion may be even higher, as the role of atrial fibrillation in the pathogenesis of stroke may be underestimated5. Strokes in patients with AF are in general severe, associated with higher risk of fatality and prone to early and long-term recurrence6.

Stroke causes 10 percent of deaths worldwide7 and is the third most common cause of death after ischaemic heart disease and all types of cancer combined8. Every year, 15 million people worldwide suffer a stroke, of whom five million die and another five million are left permanently disabled, placing a burden on family, community and healthcare resources9.


2. Costs of stroke

Stroke is preventable and yet it is a major public health problem that affects all countries10.
The American Heart Association (AHA) estimated that stroke in the US cost $57.9 billion in 2006 for both the direct costs for medical care and indirect costs from lost productivity11 . The total annual cost of stroke in Europe is estimated at €21.2 billion12 .


3. Consequences of stroke

Stroke is a medical emergency that can cause permanent neurological damage, complications and death if not promptly diagnosed and treated13.
  •  One third of people who have a stroke are likely to die within the first ten days14.
  •  A third of people are likely to recover within a month13.
  •  A third of people are likely to be left with disabilities and need rehabilitation13.

The physical damage caused by a stroke depends on the area of the brain that has been affected. The most obvious effect is hemiplegiai, paralysis of one side of the body, which can render patients immobile. Other neurological deficits include unsteadiness, weakness, impaired co-ordination, changes in sensation, neuropathici or nerve pain, speech and communication difficulties (dysphasia), which can vary from mild difficulties to being completely unable to speak. Impaired swallow (dysphagia) is common and potentially dangerous as patients can inhale food, drink or secretions, causing aspiration pneumonia or asphyxiationi2. Cognitive deficits can include difficulty remembering, concentrating, planning or recognising sounds, while visual disturbances may include double vision, losing half the visual field or losing the ability to recognise faces or even their own body15.

4. AF a major risk factor for stroke

AF, the most common cardiac arrhythmiai seen by doctors, is one of the most important risk factors for stroke1. In AF, the upper chambers of the heart, the atria, beat in an uncoordinated and disorganised way, resulting in an irregular and often rapid heart rhythm16. This irregular, rapid heart beat leads to deterioration of the heart’s mechanical function17, and slower blood flow. This slower blood flow promotes pooling of blood in the atria and formation of clots that may cause a cardioembolic stroke17.

The prevalence and incidence of AF increase with age, as does the risk of stroke.
  • In the elderly, AF is the single most important cause of stroke18.
  • AF is an independent risk factor for stroke19.
  • In patients with AF, the risk of stroke is increased 5-fold16.
  • An ischaemic stroke associated with AF is more severe than an ischemic stroke due to other causes, and this increased severity is independent of advanced age and other stroke risk factors20.
  • One study found 20.3 percent of patients admitted with acute ischaemic stroke had AF and 41.2 percent of patients with AF were bedridden compared with 23.7 percent in patients without AF (P ≤ 0.0005)20.
  • Unfortunately, AF often goes undetected and untreated because it is asymptomatic in 15-35 percent of cases21.
  • About 35 percent of patients with AF who do not receive anticoagulation treatment will have a stroke22.

5. Medical management of stroke

Stroke requires urgent treatment – thrombolysisi using ‘clot buster’ drugs can dissolve a clot in ischemic stroke if administered within the first three hours of a stroke. But this needs a confirmed diagnosis of ischaemic stroke via brain imaging23. The cornerstone of stroke prevention is anti-thrombotic therapy (including oral anticoagulant and antiplatelet agents). Oral anticoagulants, such as warfarin, are part of the standard of care in AF patients. But oral anticoagulation is prescribed for less than half of patients with AF who have risk factors for cardio-embolism complications and no contraindications for anticoagulation14.

Recently, post-hoc analysis of the ATHENA study24 on non-pre-specified secondary endpoints presented at the European Society of Cardiology (ESC) congress 2008 (Munich, Germany) showed that dronedarone (Multaq®), an anti-arrhythmic drug, decreased the risk of stroke (ischemic or haemorrhagic) compared with placebo by 34 percent (46 vs. 70 stroke events respectively; p=0.027) in atrial fibrillation/atrial flutter patients adequately treated by standard therapy including antithrombotics.

ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in PatiENts with Atrial Fibrillation/Atrial Flutter) is a double blind placebo-controlled randomised study in patients with AF, conducted in more than 550 sites in 37 countries. This study involved more than 4,600 patients excluding those with decompensated severe systolic heart failure.

 

For more information about AF, please click here.

For more information about the ATHENA post-hoc analysis in stroke, please check Press Release September 3, 2008.

For more information about dronedarone, the ATHENA study and other published clinical trial results, please click here.


References :

1. Adamson J, Beswick A & Ebrahim S. Is stroke the most common cause of disability? J Stroke Cerebrovasc Dis. 2004 Jul-Aug;13(4):171-7.
2. The Stroke Association. Physical Effects of Stroke. Factsheet 33. October 2006.
3. The Internet Stroke Center. What is a stroke? Available at: http://www.strokecenter.org/patients/about.htm. Last accessed: 5 August 2008.
4. Patient.co.uk. Stroke. Available at: http://www.patient.co.uk/showdoc/23068830/. Last accessed: 12 August 2008.
5. Stramba-Badiale M. Atrial fibrillation subtypes, risk of stroke, and antithrombotic therapy. European Heart Journal Advance Access published online on March 10, 2008. European Heart Journal, Available at: doi:10.1093/eurheartj/ehm594. Last accessed: 12 August 2008.
6. Ferro JM. Atrial fibrillation and cardioembolic stroke. Minerva Cardioangiologica. 2004, 52, 111-124
7.The World health report 2004. Annex Table 2: Deaths by cause, sex and mortality stratum in WHO regions, estimates for 2002. Geneva: World Health Organization.
8. Warlow C, Sudlow C, Dennis M, Wardlaw J, Sandercock P. Stroke. The Lancet 2003, 362, 9391:1211-1224.
9. The World Health Organization. Global Burden of Stroke. Available at: http://www.who.int/cardiovascular_diseases/en/cvd_atlas_15_burden_stroke.... Last accessed: 12 August 2008.
10. Truelsen T, Bonita R and Jamrozik K. Surveillance of stroke: a global perspective. Int J Epidemiol. 2001;30:S11-S16.
11. American Heart Association. 2002 Heart and stroke statistical update. AHA 2002 and www.strokeassociation.org.
12. Cost of Brain Disorders in Europe Fact Sheet. European Brain Council's Cost of Brain Disorders in Europe study. www.cnsforum.com/streamfile.aspx?filename=CBDE_stroke.pdf&path=pdf. Last accessed 12 August 2008.
13. Wikipedia. Stroke. Available at: http://en.wikipedia.org/wiki/Stroke. Last accessed: 12 August 2008.
14. Bosanquet N & Franks P. Stroke care: reducing the burden of disease. 1998. The stroke Association.
15. The Stroke Association. Cognitive Problems after Stroke. Factsheet 7. October 2006.
16. Fuster V et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. European Heart Journal (2006) 27, 1979-2030.
17. Medline Plus medical encylopedia. Stroke secondary to cardiogenic embolism. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000735.htm. Last accessed on August 5, 2008.
18. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998 Oct 16;82(8A):2N-9N.
19. Wolf, Philip A. MD; Abbott, Robert D. PhD; Kannel, William B. MD. Atrial Fibrillation as an Independent Risk Factor for Stroke: The Framingham Study. Stroke. 22(8):983-988, August 1991.
20. Dulli DA, Stanko H, Levine RL. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology. 2003;22:118-123.
21. Savelieva I, et al. Pacing Clin Electrophysiol. 2000;23:145-148.
22. Tong K, Hargroves D. Atrial fibrillation and stroke prevention in elderly people. Geriatric Medicine, June 2008, 337-340.
23. Patient.co.uk. Thrombolytic Treatment of Acute Ischaemic Stroke. Available at: www.patient.co.uk/showdoc/40002417. Last accessed: 12 August 2008.
24. Connolly SJ. ATHENA: The effect of dronedarone on cardiovascular outcomes and stroke in patients with atrial fibrillation. European Society of Cardiology Congress 2008; September 3, 2008; Munich, Germany. Clinical trials update

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