What treatment should be given to a person who has suffered acute ischemic stroke?
Stroke is currently the third leading cause of death in the UK and the single largest cause of adult disability in England, 11% of deaths in England are as a result of stroke. Over 300,000 people are living with moderate to severe disabilities as a result of stroke. Ischaemic stroke is the most common type of stroke and accounts for 80% of all cases of stroke. Stroke is more common in men than in women, however more women die of stroke than men (9). The question is what treatment should be given to a person that has had an ischaemic stroke
This is a type of stroke whereby a part of the brain is damaged caused by an interruption to its blood supply. The cerebral artery supplies blood (rich in nutrient and oxygen) to the brain from the heart. When this artery is blocked the brain cells stop working and after some time die.
This interruption is often due to thrombosis whereby the cerebral artery is blocked by a blood clot which has formed within it. Another cause of interruption is embolism, in this case a blood clot that has formed in another part of the body has travelled through the blood stream and blocked the cerebral artery(3). Interruption can also be caused by a blockage in the tiny blood vessels deep within the brain.
Fig 1 part of a brain that has suffered ischaemic stroke, the artery has a blockage. (15)
The left part of the brain is responsible for the right part of the body and vice versa, therefore if an ischaemic stroke occurs in the left side of the brain, the right side of the body will be affected (paralysed) (5).
Risk factors of stroke
– Prior stroke, TIA or heart diseases
– High blood pressure
–High blood cholesterol
– Lack of physical activities/exercise
Symptoms of ischaemic stroke
– Numbness, weakness, inability to move your face, leg, or arm and loss of sight on one side of the body.
–Difficulty in speech communication
–Confusion, loss of balance or coordination
– Loss of consciousness
Treatment for ischaemic stroke
Thrombolytic therapy is an immediate treatment of ischaemic stroke. Thrombolytic therapy is the use of thrombolytic drugs to dissolve the blood clot that has blocked the cerebral artery and restore blood flow to the brain.
The most commonly used thrombolytic drug is the tissue plasminogen activator (tPA), this drugs include alteplase, reteplase, prourokinase, streptokinase, tenecteplase, urokinase and many others. The choice of thrombolytic drugs will differ from patient to patient and clinical trials. Thrombolytic therapy within the first three hours of ischaemic stroke onset offers substantial net benefit, thrombolytic therapy within the first 3-4.5 hours offers a moderate net benefit (5). The advantage of thrombolytic therapy may extend up to 6 hours (4).
In thrombolytic therapy time is very important, time lost is brain lost. When an ischaemic stroke occurs the brain cells start dying, the quicker blood flow is restored to brain the fewer brain cells die. Therefore ischaemic stroke should be treated as soon as the patient has been considered eligible for the treatment. Decision to give thrombolytic therapy is based on a brain CT scan to make sure there is no bleeding or patient has not experienced hemorrhagic stroke in the past and other medical histories(8).
Mechanism action of tissue plasminogen activator (tPA)
tPA is often given as injections, When tPA is administered to the blood clot, it binds to the fibrin surface and catalyses the conversion of plasminogen to plasmin, plasmin breaks down the cross link between fibrinogen and fibrin contained in blood, fibrin molecules are broken and therefore dissolving the blood clot.
Plasminogen activators also known as fibrinolytic agent are divided into two types, fibrin-specific agent which produces limited plasminogen conversion in the absence of fibrin and non-fibrin-specific agent which do not require free circulating plasminogen to be effective. Fibrin-specific agents include alteplase, reteplase, urokinase and tenecteplase, while non-fibrin-specific agent is streptokinase (7).
Fig 2 Mechanism action of tissue plasminogen activator (tPA) also known as fibrinolytic agent.
Alteplase is fibrin-specific and effective with moderate amount of circulating fibrin on the site of clot. Tenecteplase has the same mechanism action of alteplase. Reteplase allows plasminogen to be transformed into plasmin without binding to fibrin. Urokinase binds directly with plasminogen to produce plasmin. Prourokinase is a new fibrin-specific agent undergoing clinical trials for a different kinds of indications. Streptokinase is not a plasminogen activator but binds with free circulating plasminogen converting plasminogen to plasmin. The activity of streptokinase will not be effective if fibrin is present(6).
TPA Thrombolytic trials
Since the publication of the National Institute of Neurological Disorder and Stroke (NINDS), tPA has been considered very effective for the treatment of ischaemic stroke. NINDS trial (12, 2) shows 624 patient treated with 0.9 mg/kg rtPA within 3 hours of stroke onset had a better chance of recovery with minimal or no disability 3 month after treatment. The NINDS trial for intravenous tPA produced a favorable outcome in 24 hours for 31-50% of the patient treated with compared with 20-38% of patient given placebo. Overall, for every 100 patients treated within the first 3 hours, 32 had a better outcome as a result and 3 a worse outcome.
The European Cooperative Acute Stroke Study (ECASS) I (12) randomized 620 patients to either treatment with intravenous rtPA (1.1mg/kg) or placebo within 6 hours after stroke onset. The end point statistic shows a significant increase of favorable outcome in the rtPA-treated patient group (OR, 1.5; 95% CI, 1.1 to 2.0; P=0.008). The risk of parenchyma hematoma of larger extent was increased by 8.8% in patients receiving rtPA (11.1% versus 2.3%). Treatment with rtPA did not increase the risk of hemorrhagic infarction.
ECASS II (12) evaluated the use of 0.9 mg/kg rtPA in 800 patients. Patients were randomized in a stratified manner to receive treatment within 3 to 6 hours after onset of stoke. The primary end point was a favorable (score 0, 1) and unfavorable (score 2 to 6) outcome in the primary end point in favor of rtPA treatment, but the increase of independent patients was significant (54.3%versus 46.0%; P=0.024).. The rate of parenchyma hematoma type2 was increased 10-fold in rtPA-treated patients (8.1% versus0.8%). The absolute treatment differences in ECASS II were very similar in those patients treated in the first 3 hours of stroke compared with those treated between 3 and 6 hours.
Fig 3 Tissue plasminogen activator (tPA) trials by NINDS and ECASS.
The favorable results of the ECASS trials in the 6 hour window have been duplicated in a large phase 4 study examining the use of intravenous tPA in routine clinical practice. The international Safe Implementation of Treatment in Stroke (SITS) (6) prospective registry identified 2376 patients treated in the 3- to 4.5-hour window in regular practice at 650 centers from more than 25 countries. The rates of complications and of favorable outcomes were similar to those in ECASS. These findings confirm tPA as effective in clinical practice as it is efficacious in clinical trials in the 3- to 4.5-hour window when inclusion and exclusion guidelines are followed.
In May 2009, the American Heart Association/American Stroke Association (AHA/ASA) guidelines for the administration of recombinant tPA (rtPA) following acute stroke were revised to expand the window of treatment from 3 hours to 4.5 hours to provide more patients with an opportunity to receive thrombolytic therapy but not have been FDA approved (6).Tenecticase appears effective thrombolytic agent with fewer bleeding. A clinical trial of streptokinase was stopped because of high rate of hemorrhage. Alteplase is a safe and effective treatment in carefully selected stroke patient, currently new evidence has shown that alteplase is effective if administered within 4.5 hours of stroke symptoms (11).
Implications of thrombolytic therapy
A third of people who have a stroke are left with long-term disability. The effects can include aphasia, physical disability, loss of cognitive and communication skills, depression and other mental health problems (9). There is no doubt thrombolytic therapy is effective in the treatment of ischaemic stroke. With thrombolytic therapy patient is not left disabled, this means they are able to socialize, work and do not get frustrated due to the taught of being useless in life, this is helps eliminate feeling of depression.
If a person is treated with thrombolytic therapy it will be possible for the person to recover and gain back his or her ability after about three month. The patient does not need to be dependent on others and can have a proper life because they do not have to rely on medical care for a long period of time. Thrombolytic therapy also reduce/eliminate the strain of poverty on the patients or their family because the person is able to work, also they do not spend lots of money on medical care, thereby saving money for other necessary things. Thrombolytic therapy also helps reduce the number of death in stroke sufferers which reduces loss of friends and family members.
While the majority of people survive an ischemic stroke, many are left with some form of disability, up to a third of sufferers remain functionally dependent one year after their stroke, requiring long-term medical care or institutionalization. This results in considerable healthcare costs. In the US, stroke costs more than $56.8 billion annually, 62 % of which is accounted for by hospital and home care costs. While in Europe, stroke management accounts for 5-10% of healthcare resources (10).Thrombolytic therapy helps ischaemic stroke patients recover their ability quickly and reduce the severity of disability, this means that patient will require less treatment or long term care after stroke. Therefore the health care cost can be reduced through thrombolytic therapy.
If a person is disabled due to ischaemic stroke he or she is unable to go to work and therefore there is a loss of member of the workforce. With all the ischeamic stroke patient left disabled, there is a very huge impact on the economy because there is loss of economic productivity. A Patients treated with thrombolytic therapy is able to gain their ability quickly and can go back to work, this result to an increase in economic productivity.
Benefits and risks
Thrombolytic therapy have been used for years in the treatment of ischaemic stroke and have been found very effective .Thrombolytic therapy dissolves the blood clot in the artery and helps restore blood supply to the brain. This reduces the effect of stroke and the level of disability for some people.
However the treatment does not always dissolve the blood clot because they vary in sizes and make-up. Overall more people may get better with thrombolytic treatment, about one person in ten people treated will make a better recovery than expected (9). Thrombolytic therapy increases the chance of a patient being independent of others after stroke and can reduce the chance of a patient dying after suffering ischaemic stroke. Thrombolytic therapy can be effective without the need of invasive surgery which can also lead to a shorter hospital stay.
However thrombolytic therapy has its own side effects some of which include hemorrhage, allergic reactions, embolism, fever, reperfusion arrhythmias and infection at the site of injection. There is risk of kidney infection in people with kidney diseases like diabetes
The most complicated side effect is hemorrhage, because tPA dissolves blood clots there is a high risk of bleeding. Sometime a small amount of blood can be oozing from the site of injection, this is minor bleeding, but however major bleeding can occur this includes bleeding in the brain. Bleeding also occur in other part of the body. Overdoses of Thrombolytic drug leads to severe complications of hemorrhage. Severe bleeding causes a bad outcome of thrombolytic therapy.
Miscarriage may occur if thrombolytic drug is used during the first five month of pregnancy. People who take certain medicines like blood thinners and antiseizure medicine is at a higher risk for severe bleeding if given thrombolytic drug. (2, 6). The risks of thrombolytic therapy should carefully be weighed against the benefits before thrombolytic therapy is commenced.
Mechanical thrombectomy is a procedure which involves the removal of blood clot directly from the site of blockage without the clot being dissolved. This is done by directing a catheter from the femoral artery to the blocked artery in the brain, once the catheter has reached the clot, it is placed in good position to trap the clot. After the clot is trapped, the catheter and the clot are then withdrawn from the body. Once blood clot is successfully removed blood supply is restored to the brain.
Fig 4 Two mechanical thrombectomy device (L5 and X6) used in retrieving blood clot. (1)
The various devices can be divided into 2 major groups according to where they apply force on the blood clot: proximal devices (PDs) and distal devices (DDs). Proximal devices apply force to the nearest site of the blood clot. Distal devices (DDs) approach the blood clot proximally but then are advanced by guide wire and micro catheter past the blood clot to be unsheathed behind it(1).
Mechanical thrombectomy has a wider time window of up to 8 hours. The benefits of this procedure include an advantage of safety by leading to fewer bleeding complications, because they can reduce the use of thrombolytic drug d, or eliminate them altogether from the treatment. However mechanical thrombectomy also have its side effects, because the device is inserted into arteries, it also can damage to the walls of the artery. Mechanical thrombectomy in the treatment of acute ischemic stroke seems to provide an option for some patients who arrive after the time window, are not eligible for tPA or do not respond to thrombolytic therapy.
Angioplasty and stenting is mostly used in treating artheriosis in coronary artery diseases, peripheral artery disease and renal vascular hypertension. This method takes about an hour. Sometimes the patient is awake during the procedure and may fell little or no pain. After the procedure the patient is sometimes hospitalized for 24 hours so that signs of complications can be monitored (14).
However, inserting a catheter into an artery can lead to injury of the artery, in some cases artery can narrow after some weeks of treatment. Allergy reaction can occur if contrast material like dye is injected. Dislodged blood clot can cause a blockage in another part of the body.
This is a website owned by the American stroke association which is a well known and trusted and therefore information can considered valid in terms of were it has come from. They publish lots of peer reviewed article about cerebral circulation and diseases associated with it. The articles are written by authors who are specialized and expert in field of cerebral circulation therefore the information are gotten from this source is said to be of good quality and standard standards. The information gotten from this source is said to be valid since other sources [like NHS (9, 5) and National STROKE strategy (3)] also agree with it. This source is also a non-profit organization which significantly provides better quality information than commercial sources which are more likely to be compromised by a desire to sell a certain product. Also the information on this source is referenced and being updated on a regular bases. I have e found this source very reliable and therefore conclusion and information can be drawn from it.
eMedicine is a website part of the WebMD Health Professional Network which includes Medscape.com and theHeart.org. It is a website that publishes article about different kinds of disease and medical topics. The articles published on this website undergo several levels of physician peer review with an additional review by a PharmD before they are published. This source makes sure their authors are specialised in the field of the articles and all information is referenced and updated regularly. This source is not a non profit organisation so I can not say the source is trusted because there may be a possibility that the information is being compromised because of the desire to sell a product, but most importantly the articles are peer reviewed so every information must have been checked and reviewed with other source before they are being published.
American stroke association.(2008) mechanical thrombectomy for acute ischaemic stoke http://stroke.ahajournals.org/cgi/content/full/39/4/1205 (accessed on 19 Jan 2011)
Medscape. Author: Wanda L Rivera-Bou. (2002) Thrombolytic therapy. http://emedicine.medscape.com/article/811234-overview (accessed on 9 Jan 2011)
DH/Vascular programme/Stroke. (2007) National STROKE Strategy, London. DH Publications.
Wikipedia the free encyclopedia (2004). Stroke.http://en.wikipedia.org/wiki/Stroke (accessed on 7 Jan 2011)
NHS (2009) Stroke. http://www.nhs.uk/Conditions/Stroke/Pages/Introduction.aspx (accessed on 7 Jan 2011)
Medscape. (2007) Fibrinolytic agents. http://www.medscape.com/viewarticle/565764_3 (accessed on 10 Jan)
7. Medscape. Author: Jeffrey L Saver. (2004) Thrombolytic therapy in stroke http://emedicine.medscape.com/article/1160840-overview (accessed on 14 Jan 2011)
Wikipedia the free encyclopedia. (2006) Thrombolytic drugs http://en.wikipedia.org/wiki/Thrombolytic_drug (accessed on 17 Jan)
NHS Islington (2009). Stroke. http://www.islington.nhs.uk/stroke.htm (accessed on 8 Jan 2011)
Medical news today (2006) economical impact of stroke http://www.medicalnewstoday.com/articles/38411.php (accessed on 20 Jan 2011)
Julien Bogousslavsky, Werner Hacke (2006) Thrombolytic and Antithrombotic for stroke. United Kingdom. Informa UK Ltd.
American stroke association (2002) thrombolytic therapy within 3 to 6 hours after ischaemic stroke onset http://stroke.ahajournals.org/cgi/content/full/strokeaha;33/5/1437 (accessed on 14 Jan 2011)
305brodcast (2009) stent. http://305broadcast.com/docs/?p=stent (accessed on 18 Feb)
Radiologyinfo.org (2010) angioplasty and vascular stenting http://www.radiologyinfo.org/en/info.cfm?pg=angioplasty (accessed 22 Jan)
Health.com (2010) ischemic stroke. http://www.health.com/health/library/mdp/0,,hw222796,00.html (accessed on 18 Feb.)