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.
Antiarrhythmics
There are 4 classes of antiarrhythmics according to the Vaughan-Williams classification system
Class I: Sodium Channel Blockers
• Class IA – Moderate
o Ex. Procainamide, Quinidine, Disopyramide
♣ Moderate influx of sodium during depolarization and prolong the action potential duration by blocking sodium channels
♣ They also have some potassium channel blocking activity which further prolongs repolarization
♣ Results in decreased conduction velocity, increased refractory period and stabilization of myocardial membranes.
♣ Essentially the drugs in this class slow down sodium influx, prolong the action potential and refractory period, and stabilize the heart's rhythm by preventing abnormal electrical signals from spreading.
• Class IB – Fast
o Ex. Lidocaine, Mexiletine
♣ The drugs in this class bind to inactivated sodium channels in depolarized tissues, such as in damaged areas of the heart. They rapidly associate and dissociate from sodium channels, causing minimal effects on normal cardiac tissue. These drugs decrease conduction velocity and shorten the action potential duration, making them effective in treating ventricular arrhythmias.
• Class IC - Potent
o Ex. Flecainide, Propafenone
♣ These drugs bind strongly to sodium channels with a slow dissociation rate, significantly reducing sodium influx and slowing conduction velocity in all cardiac tissues. They do not prolong the action potential duration, making them effective for both atrial and ventricular arrhythmias. These drugs can suppress abnormal electrical activity while having minimal effects on normal conduction.
Class II: Beta Blockers
• MOA: Beta blockers block beta-adrenergic receptors in the heart which reduce effects of adrenaline, slows heart rate by decreasing firing from the SA node, slows conduction through the AV node, and decreases force of contraction
• Selective Beta-1 Blockers
o Beta 1 receptors are primarily found in the heart, therefore, beta 1 selective blockers primarily affect the heart
o Has minimal impact on the lungs, safer for patients who have COPD or asthma
o Ex. Metoprolol, Atenolol, Esmolol, Bisoprolol, Nebivolol
• Non-Selective Beta Blockers
o Beta 2 receptors are found in the lungs. When a beta blocker is nonselective it binds to both beta 1 receptors and beta 2 receptors which can lead to broader effects
o Beta 2 receptor blockade can cause bronchoconstriction, which can be problematic in patients with respiratory issues.
o Ex. Propranolol, Nadolol, Sotalol, Carvedilol
Class III: Potassium Channel Blockers
• MOA: Block potassium channels, which prolongs the action potential and refractory period in the heart. This helps in stabilizing heart rhythms and preventing arrhythmias.
o Amiodarone - blocks multiple channels (potassium, sodium, and calcium), which prolongs action potential duration, also has alpha- and beta-adrenergic blocking effects.
o Dronedarone- blocks multiple channels (potassium, sodium, and calcium) and also exerts antiadrenergic properties- similar to amiodarone, less toxicities, do not use in patients with heart failure
o Sotalol- dual action, blocks both beta receptors and potassium channels
o Ibutilide – pure class 3 drug, blocks potassium channels
o Dofetilide- pure class 3 drug, blocks potassium channels
Class IV: Nondihydropyridine Calcium Channel Blockers
• MOA: block L-type calcium channels in the cardiac muscle and vascular smooth muscle. This blockade reduces calcium influx during depolarization. This leads to reduced heart rate, reduced AV node conduction, and reduced contractility.
o Diltiazem, Verapamil
Other antiarrhythmic drugs not included in the Vaughan-Williams classification system include:
• Adenosine
o Works by activating A1 adenosine receptors in the heart, leading to slowed conduction through the AV node and decreased automaticity. It is effective for terminating certain types of supraventricular tachycardias due to its rapid onset and short duration of action.
• Digoxin
o Works by inhibiting the NA/K ATPase pump, leading to increased intracellular sodium and calcium levels, which enhances cardiac contractility. It also slows conduction through the AV node, making it useful in managing certain arrhythmias like AF.
https://my.clevelandclinic.org/health/drugs/22867-what-are-antiarrhythmics
UWorld RxPrep NAPLEX Review 2025 Chapter 32 Arrythmias Page 454