Cardiac arrhythmias are common causes of cardiac related morbidity and mortality. If the heart does not properly beat in a normal rhythm, there can be many issues in terms of clotting and possible venous thromboembolisms. Atrial fibrillation is the most common cause of cardiac arrhythmias. It is the number one cause of cardiac related stroke. When the blood in the heart is not properly and efficiently ejected, there can be stasis and pooling of the blood in the heart. This can lead to a clot forming in the atria of the heart. When this clot becomes dislodged, it can travel to the brain and block the blood flow to the brain. In order to prevent the formation of clots in the atria of the heart, people with atrial fibrillation are placed on anticoagulants. This will thin the blood and decrease the risk of a stroke. Typically, people with atrial fibrillation are placed on either warfarin or a direct-acting oral anticoagulant (DOAC). Warfarin is a burdensome drug for patients to be on life-long. It requires therapeutic drug monitoring, and there are many interactions with foods, medications, and supplements. Any small change in a patient’s lifestyle can have drastic effects on their INR level.(1) Edoxaban is a direct factor Xa inhibitor, and does not have any therapeutic monitoring required. It has not, however, been compared to warfarin for the treatment of atrial fibrillation after a transcatheter aortic-valve replacement (TAVR).
In a multicenter, prospective, randomized, open-label trial comparing edoxaban versus vitamin K, over 21,000 patients were enrolled. The primary endpoint was a stroke or some kind of systemic embolism. Patients who were enrolled in the study had moderate or severe risk atrial fibrillation. The rate of the primary endpoint in the warfarin arm was 1.50%, while the rate of the primary endpoint for the edoxaban arm was 1.13%. Although these percentages might not look much different, this number could still save lives. The dose of the edoxaban that was effective was a high dose of 60 mg and the lower dose of 30 mg. Edoxaban was shown to be non-inferior to warfarin. Edoxaban also offers convenience and lack of monitoring as compared to warfarin. Edoxaban also showed to reduce major bleeding events, all cause cardiovascular death, and a composite of strokes, systemic embolism, or death from any cardiovascular cause. These results are significant in terms of the safety and efficacy of an anticoagulant regimen. For patients on anticoagulants, the biggest risk is the risk of bleeding. Both warfarin and edoxaban are reversible anticoagulants. The risk associated with edoxaban is lower than warfarin, and might be a more appropriate therapy for patients with a high fall and bleeding risk. (2)
When evaluating two treatment options, it is important to consider patient specific parameters. Patients with renal impairment have a dose adjustment with edoxaban. This might be specifically relevant for patients with concomitant kidney disease. Patients who are unable to present for follow-up INR visits are more likely to be initiated on some other kind of anticoagulant, such as edoxaban. It is essential to have multiple options for patients, as every patient has different needs. This trial shows that edoxaban is another tool for patients with atrial fibrillation.
References:
Nesheiwat Z, Goyal A, Jagtap M. Atrial Fibrillation. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526072/
Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104.
Atrial fibrillation (AF) is the most frequently managed cardiac arrhythmia. It typically presents with a ventricular rhythm that is “irregularly irregular” and lacks distinct P waves. Different types of AF are categorized based on the duration and frequency of the episodes, as outlined in the guidelines on AF management from the AHA. The four distinct types are paroxysmal, persistent, long-standing persistent and permanent AF:
Paroxysmal: self-terminating or intermittent patterns, AF that spontaneously ends or requires intervention within 7 days of onset. Recurrences in episodes may vary in frequency.
Persistent: AF that persists beyond 7 days without self-termination. This type of AF usually necessitates pharmacological therapy or electrical cardioversion to restore the normal sinus rhythm.
Long-standing persistent: AF that has lasted for longer than 12 months
Permanent: AF in which both the patient and the healthcare provider have decided not to pursue a rhythm control strategy.
In terms of clinical presentation, patients with AF may or may not present with a number of symptoms. Typical signs and symptoms of AF include but are not limited to palpitations, tachycardia, fatigue, weakness, dizziness and increased urination. In addition, some patients may present with more severe symptoms which include chest pain, dyspnea at rest and symptoms of heart failure (peripheral edema, sudden weight gain, abdominal swelling from ascites, dyspnea on exertion). For all patients who are suspected of having new-onset AF, a 12-lead ECG is conducted. As briefly aforementioned, ECGs showing AF reveal no discernible P waves but instead show rapid, low-amplitude, continuously changing fibrillatory waves. Furthermore, the ECG typically also reveals a lack of a consistent pattern of the ventricular rhythm and rather the rhythm is seen as “irregularly irregular.”
Clinical management of AF involves both pharmacological and nonpharmacological interventions. Nonpharmacological approaches in the treatment of AF primarily involve lifestyle changes that are “heart-healthy.” These recommendations include targeting for a healthy weight to lessen the severity and number of AF episodes (which may be done through increasing physical activity), limit or avoid alcohol or other stimulant intake that may increase the heart rate, quit or reduce smoking, and implement a heart-healthy diet such as the DASH plan, which recommends reducing salt intake to lower blood pressure. For pharmacological interventions, the two primary approaches to treatment are rhythm versus rate control.
Rhythm control is often pursued in cases where patients experience substantial symptoms that limits their activity and negatively impacts their quality of life. The rhythm control strategy is preferred in patients who are no greater than 80 years of age. This is because in comparison to older patients, younger individuals typically experience fewer adverse reactions from rhythm control agents. Furthermore, younger patients are also less prone to developing permanent AF, which enhances the prospects of successful cardioversion and the sustained maintenance of sinus rhythm. Rhythm control is also preferred in patients that are deemed to be at high cardiovascular risk, irrespective of their symptoms. High risk for cardiovascular disease is defined by specific criteria such as age over 80 years, a history of transient ischemic attack or stroke, or meeting two of the following criteria: age over 65 years, female gender, history of heart failure, hypertension, diabetes, severe coronary artery disease, CKD and left ventricular hypertrophy. Examples of common rhythm control agents are sodium channel blockers such as Flecainide and Propafenone and potassium channel blockers such as Amiodarone, Sotalol and Dofetilide.
On the other hand, rate control agents are preferred in patients who are older than 80 years, are asymptomatic and present with a low cardiovascular risk. This is due to the fact that rate control agents are associated with fewer adverse reactions compared to rhythm control agents. Individuals who are greater than 80 years old are particularly more sensitive to the proarrhythmic effects of antiarrhythmic medications which can lead to further complications. In fact, results from the AFFIRM and RACE trials suggested that rate control with antiarrhythmic medications yielded outcomes that were equivalent, if not superior, to those who were taking rhythm control agents. Common examples of frequently prescribed rate control medications are beta blockers such as Bisoprolol, Carvedilol and Metoprolol, calcium channel blockers such as Diltiazem and Verapamil and cardiac glycosides such as Digoxin.
Resources:
Kumar K. Atrial fibrillation: Overview and management of new-onset atrial fibrillation. UpToDate. October 31, 2023. Accessed April 24, 2024. https://www-uptodate-com.jerome.stjohns.edu/contents/atrial-fibrillation-overview-and-management-of-new-onset-atrial-fibrillation?search=atrial+fibrillation&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H5.
Atrial Fibrillation - Treatment. National Heart Lung and Blood Institute. November 30, 2022. Accessed April 24, 2024. https://www.nhlbi.nih.gov/health/atrial-fibrillation/treatment.
Kumar K, Manning W. Management of atrial fibrillation: Rhythm control versus rate control. UpToDate. June 26, 2023. Accessed April 24, 2024.
Atrial fibrillation medications. heart.org. December 21, 2023. Accessed April 24, 2024. https://www.heart.org/en/health-topics/atrial-fibrillation/treatment-and-prevention-of-atrial-fibrillation/atrial-fibrillation-medications.