Introduction

Stroke and heart failure are comorbid conditions that have huge implications for global health.  Strokes are the leading cause of death and disability due to damage to the tissue in the brain caused by the interruption of blood supply to the brain. Heart failure is a condition in which the heart fails to pump enough blood; often, this condition is associated with an enlarged heart.¹

Many of the risk factors for stroke also occur in heart failure, including atrial fibrillation, hypertension, and diabetes. The poor cardiac output results in thrombus formation, especially in the presence of ventricular dysfunction. These clots embolize to the brain and result in ischemic or "silent "strokes, leading to cognitive impairment in heart failure patients.

Anticoagulants are drugs used to prevent clotting, hence lowering the incidence of a stroke. This article addresses heart failure aetiology in stroke, and provides insight into the mechanisms behind anticoagulation as an effective stroke prevention and treatment.

Understanding heart enlargement and its link with stroke 

Cardiomegaly or heart enlargement is referred to as the enlargement of cardiac chambers, often including the left atrium or left ventricle. It typically reflects an increased workload upon the heart or an existing underlying disease that results in the altered structure of the heart. Hypertension, valvular heart diseases like mitral valve regurgitation, and cardiomyopathies or diseases of the heart muscle are some of the primary causes of heart enlargement. All these conditions require that the heart pump harder, to ensure adequate blood flow; this forces the heart muscle or chambers to either thicken or dilate.²

One of the most important mechanisms by which enlargement of the heart results in a stroke is through a change in blood flow within the left atrium. Blood begins to stagnate due to compromised blood flow in the system with enlarged atria. Stagnated blood creates a breeding ground for clots, mostly formed in the appendage of the left atrial chamber. The small, pouch-like appendage allows blood to stop flowing due to its shape and leaves it open to the occurrence of clots, which easily detach and go directly to the brain, leading to an ischemic stroke.³ This risk is heightened by AFib (atrial fibrillation), which is an irregular heart rhythm. In the presence of an enlarged left atrium, patients with this disease cannot contract their atria sufficiently, thereby impeding blood flow and increasing the chances of a clot. Studies have shown that a person with AFib is more prone to suffer from a stroke than one without it because AFib causes the formation of blood clots within a short period of time due to the abnormal and inefficient contractions of the atria.⁴

In light of this, heart enlargement, specifically left atrial enlargement, and diseases like AFib pose a serious threat to the risk of having a stroke, and controlling the size of the heart and its rhythm are important in stroke prevention.

How anticoagulants work to prevent stroke 

Anticoagulants form a major component in preventing stroke, especially in a patient with a predisposition to thrombus formation. The basic mechanism involved with the action of most anticoagulants is the inhibition of one or more of the coagulation factors, resulting in the prevention of an ischemic stroke. They are different from drugs, which are antiplatelets, as they do not allow aggregation of platelets towards inhibition of clot formation and affect several pathways of the coagulation cascade, providing protection in cases in which blood flow is restricted.⁵

An example is warfarin, which is a traditional anticoagulant acting as an antagonist to vitamin K. It inhibits the production of vitamin K-dependent clotting factors (II, VII, IX, and X) in the liver, by binding to the receptor in place of its normal enzyme, thus lowering the potential for clotting in blood. ⁶ However, monitoring is often required, and adjustment of dosage is needed as well, making it a less convenient option than more modern alternatives.

The newer DOACs (Direct Oral Anticoagulants) include apixaban, rivaroxaban, and dabigatran. Apixaban and rivaroxaban inhibit factor Xa, while dabigatran directly acts on thrombin or factor IIa. The pharmacokinetics of these agents are predictable, thus do not require monitoring in most cases, making them easier for patients to self-manage.⁷

Anticoagulants are usually prescribed to patients with heart enlargement since the patients are likely to suffer from blood clotting due to the stagnation of blood, especially in the left atrium. Since anticoagulants inhibit blood clotting, the incidence of stroke within this population is drastically reduced. In the comparison between anticoagulants and antiplatelet drugs, anticoagulants are usually effective in preventing thrombi arising from heart conditions, thus helping prevent stroke.^8,9

Clinical evidence for the use of anticoagulants 

Indeed, there has been broad consensus on the efficacy of anticoagulant therapy among patients at high risk who are symptomatic with lower-extremity revascularized PAD. A definitive large-scale trial demonstrated the association of rivaroxaban (2.5 mg twice daily) combined with aspirin to achieve a15% reduction of all acute limb ischemia with major amputation or by myocardial infarction, ischemic stroke or cardiovascular death. This benefit was seen as early as three months after the treatment and persisted over time, which means that rivaroxaban was effective in this clinical case.¹⁰

However, these benefits come with associated risks,  the most notable of which is bleeding. Although rivaroxaban poses a risk of bleeding, its ability to reduce stroke in patients with heart enlargement may more than offset these risks for particular populations. Whereas anticoagulants are expensive and have adverse risks, they prevent many severe events, including a stroke and myocardial infarction.

Research has shown that apixaban¹¹ is significantly more effective in reducing the risk of stroke and systemic embolism than warfarin, with lower rates of bleeding in patients with atrial fibrillation. An optimum level of consideration of the safety profile with the preventative benefits of anticoagulants should be given to optimise treatment strategies in at-risk populations, so that patients are able to receive a highly effective treatment with minimal potential side effects. 

Guidelines and recommendations for anticoagulant use 

According to the AHA guidelines,¹² anticoagulant therapies need to be individualised in the treatment of patients. Thorough assessment of risk factors, patient preferences, and history is required to determine the appropriate anticoagulant for a patient. The CHA2DS2-VASc score is used to assess the annual risk of thromboembolic events and guides decisions about anticoagulation. However, for a patient with an intermediate risk score, further evaluation of other risk variables is critical.

Other specific stroke risk modifiers should be considered, especially for patients with AF at low to intermediate annual risk (<2%) of ischemic stroke. Such factors include AF burden, non-modifiable risk factors such as sex, and dynamic modifiable risk factors such as controlling blood pressure. Such discussions help in deciding on the benefits and risks of anticoagulation and ensuring treatment in the best interest of the patient based on his or her particular set of circumstances. Flexibilities in anticoagulant selection are vital in optimising patient outcomes and reducing risks.

Summary

Anticoagulants are highly essential drugs for the prevention of stroke in patients who suffer from conditions like atrial fibrillation, heart enlargement, and peripheral artery disease. These drugs inhibit blood clotting, which significantly reduces the chance of thrombus formation and ischemic strokes. Evident benefits of anticoagulants are both the efficacy of drugs, such as warfarin or direct oral anticoagulants (DOACs), apixaban, rivaroxaban, and dabigatran, in reducing strokes and maintaining good safety profiles over other treatments.

There is hope for future advances in anticoagulant therapies. New agents and novel delivery systems are being explored for efficacy and safety while minimising the risk of bleeding complications. Personalised medicine approaches will lead to more individualised anticoagulation strategies based on individual patient characteristics and risks.

Proper assessment of patients, monitoring, and administration of prescribed treatments cannot be overemphasised. Ongoing assessment of the risk factors for stroke and potential drug interactions are the hallmark of anticoagulation. Constant monitoring ensures optimal therapeutic levels are maintained and therefore adverse effects are minimised while the benefit is maximised. Thus, as healthcare continues to evolve, the incorporation of these practices will be of paramount importance to improving outcomes in patients and reducing the burden of stroke in those at risk.