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Risk Factor Atrial Fibrillation : Stroke

With atrial fibrillation there is a risk of clot formation in the heart, and if the clot dissolves there is a threat of stroke. Preventive steps can include medication (anticoagulant) or a closure system (occluder).

Human blood is not simply some sort of "special juice" but in fact a highly complex liquid. As long as it is in motion, it remains liquid. If blood is not moving fast enough, initially smaller aggregates are formed (so-called rouleaux formations).  If the blood is moving very slowly or there is a cessation of movement, this causes the blood to clot (thrombus).
 
During atrial fibrillation, the atria are greatly enlarged, in turn, their ability to contract (contractility) is reduced and thus the pumping power is very low. This is particularly true for the left atrial appendage. The left atrial appendage (see Fig. 1) is an appendage of the antechamber, which strongly contracts during the sinus rhythm and thus ejects the blood contained. With atrial fibrillation the flow velocities decrease in the left atrial appendage: There is then a risk of blood clot formation. Such clots can be readily detected using echocardiography (TEE). If atrial fibrillation lasts for a longer period of time (more than 48 hours), the risk of the formation of thrombi is particularly high.
 
Schlaganfallrisiko Vorhofflimmern: 90% aller Blutgerinnsel entstehen im LAA.
Figure 1: Computer-generated tomographic representation of the left atrial appendage. Left: 3D view of the heart. Area with white border is the atrial appendage (to the right an enlargement). Right: 2D representation of the atrial appendage. The "ribbing" in the magnification (right) are a type of small muscle bands (so-called moderator bands; septomarginal trabecula).

When a blood clot dissolves, it may cause a stroke 

If, for example, thrombi that form in the atrial appendage become loose, they can be transported by the circulatory system.  If these thrombi then get into smaller blood vessels, they can clog the vessel.
A stroke can occur if those affected blood vessels are in the brain. The incidence of thrombus forming can be reduced by the administration of anticoagulant drugs. Drugs that inhibit blood clotting, commonly known as blood thinners, reduce the occurrence of blood clots (anti-coagulation). However, since bleeding may occur as a side effect of anticoagulation, the decision as to whether anticoagulation therapy is actually required must be carefully considered in advance.
 
Blutgerinnsel  (Thrombus) im Vorhofohr: TEE Untersuchung (Schluckecho)   Blutgerinnsel im Vorhofohr
blood-clot within the left atrial appendage (LAA) Thrombus in a echo-movie.

Stroke Risk in Atrial Fibrillation 

Patients with atrial fibrillation are five times as likely to suffer a stroke as a person in the general population or patients without atrial fibrillation. It does not matter whether the atrial fibrillation (AF) occurs occasionally or is a chronic condition. Appropriate treatment (permanent anti-coagulation) can prevent two out of three strokes caused by atrial fibrillation. The new guidelines (2010) of the European Society of Cardiology (ESC) recommend anti-thrombotic treatment for atrial fibrillation for different patient groups. For each individual risk assessment, numerous studies have to be performed. On the basis of score systems the risk can objectified:
 
 

The CHA2DS2VASc Score

Point systems (so-called scores) have been developed which allow for an assessment of risk. Currently, the most widely-used is the CHA2DS2-VASc score.  With a low CHA2DS2-VASc score the use of aspirin for the prevention of stroke is sufficient. A high CHA2DS2-VASc score requires treatment with a drug selected from the group of anti-coagulants. Because these drugs are available in tablet form, it is referred to as oral anti-coagulation. One of the most established medications in this category is phenprocoumon, marketed under the brand name of Marcumar® or Coumadin, it inhibits the formation of blood clotting substances for which the vitamin K is required. It is important to identify who is at high risk for stroke. This is because each anti-coagulant drug carries the risk of bleeding complications. Therefore, in addition to the risk for the occurrence of stroke, each individual’s potential risk of bleeding must be determined. 
 

ESC*-Recommendations for Antithrombotic Treatment for Atrial Fibrillation 

The guidelines of the ESC recommend treatment for various patient groups. They use a graded system of different levels to set the recommendations. The levels, based on the results of large clinical trials and studies, were produced by a committee of experts. The highest recommended levels from the ESC are for the following patient groups: 
*European Society of Cardiology
 

Efficacy of Oral Anticoagulants in Atrial Fibrillation

Clinical studies have demonstrated the effectiveness and necessity of anti-coagulant therapy in atrial fibrillation. However, initiating treatment is a lengthy process. It takes several days before the full effect is achieved. The effectiveness is influenced by many factors. 
Food that contains a large amount of vitamin K inhibits the effect of the medication, whereby partaking of foods with low levels of vitamin K increases the effectiveness. If bleeding occurs, it may take more a longer period of time (a few days) before normal blood clotting is completed. Therefore, prior to surgery Marcumar ®must often be discontinued.
 
If Marcumar ® is used therapeutically, the effectiveness must be monitored regularly. This is done by taking a blood sample and determining the INR (International Normalized Ratio).  Previously, the so-called Quick value was determined for this purpose. The INR is comparable and can be measured by the family physician, whereby, with INR there is also the possibility of testing the level yourself. A major contraindication (factor) is the risk of bleeding which may result. This must be weighed very carefully to assess which risk is higher: a stroke or a hemorrhage. To estimate this, risk assessment scores such as the HASBLED score have been introduced.
 

 

Thrombin inhibitors and Factor Xa inhibitors

New classes of compounds for stroke prevention 
In almost all studies, the inhibition of vitamin K has been shown to have clear superiority and an unequivocal (incontrovertible) benefit for stroke prevention. 
 
Difficult manageability, the need for frequent blood samples in order to test coagulation, the influence of diet on the effect of blood clotting – all these aspects make everyday life for many patients much more difficult than is desirable for a long-term medication. 
Modern medication should therefore fulfill the following requirements: 
 
  • Predictable effectiveness 
  • Reduction of clotting tests 
  • Fast action and onset of effectiveness, as well as 
     quick abatement of effects in cases of bleeding 
  • Good manageability
  • Easy medication regimen (procedure)
 
The advantages of a number of drugs from the group of so-called direct thrombin inhibitors over conventional therapy with the more commonly used phenprocoumon were demonstrated in the first phase II and phase III clinical trials.  The first licensed medication from this new class of drugs is Dabigatran (also known as Pradaxa) which has been approved and is now available for the prevention of stroke in atrial fibrillation. The rapid onset of effectiveness (30 mins. - 1 hour), its ease of ingestion and the absence of a need for routine coagulation controls facilitate treatment for both doctor and patient.
 
In large-scale studies this substance group has demonstrated an ability to reduce the rate of stroke by 34 %, without an increase of severe bleeding. 
Professional societies in the United States (The American College of Cardiology, The American Heart Association and The Heart Rhythm Society) have all subsequently changed their guidelines for stroke prevention and recommend the use of Dabigatran as an "alternative" to vitamin K antagonists ( Warfarin).
 
For physicians and patients, this attractive new class of drug offers improved effectiveness as well as simpler application. With no side effects which affect the kidney or liver, there is no longer a need for blood sampling to test coagulation parameters.