Evaluation and Management of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common clinically encountered arrhythmia affecting 0.4% of the general population. Its prevalence increases with age, affecting more than 6% of people over 80 years of age. The annual risk of ischemic stroke in patients with lone AF is approximately 1.3%. This annual risk increases up to 10% -12% in patients with a prior stroke or transient ischemic attack. Randomized clinical trials (RCT) comparing adjusted-dose oral anticoagulation and placebo showed a risk reduction of 61% (95% CI 47% to 71%). The absolute risk reduction for stroke with oral anticoagulants is about 3% per year. Aspirin has been shown in meta-analyses to have on average a 20-25% relative risk reduction, and is inferior to oral anticoagulants. In high risk patients with AF warfarin is a class I ACC/AHA indication unless there is a contraindication for anticoagulation. Unfortunately, this therapy requires frequent monitoring with blood samples and the interaction with food and several medications makes its use difficult and sometimes unreliable. It requires strict patient compliance and its use is also linked to potentially serious bleeding complications. In clinical practice, less than 60% of patients who do not have contraindications to oral anticoagulation are actually receiving them. Additionally, of those that receive oral anticoagulation, less than 50% are consistently within therapeutic targets. As such, the "real world" efficacy of a strategy towards prescribing oral anticoagulants is likely significantly lower than that demonstrated in clinical trials. As such, the need to discover other methods of anticoagulation with oral bioavailability, predictable pharmacokinetics, and minimal interactions with diet and other pharmacological agents is imperative. Low molecular weight heparin has a more predictable bioavailability and a longer half-life, but its subcutaneous mode of administration and long-term risks, in particular, osteoporosis makes the chronic use of this medication non-feasible. Antiplatelet agents such as clopidogrel have proven efficacy and superiority compared to aspirin to prevent systemic vascular events in at-risk patient populations, but currently they do not play an important role in the prevention of AF related thromboembolic events. The ACTIVE study is a randomized trial comparing the combination of clopidogrel and aspirin therapy to oral anticoagulation with warfarin in patients with AF, and was unfortunately terminated prematurely by the data safety and monitoring board because of increased events in the antiplatelet arm. Direct thrombin inhibitors, such as ximelagatran, may be as effective as warfarin for stroke-risk reduction in patients with AF. No anticoagulation monitoring is needed and it has excellent bioavailability, with a twice-daily oral dose. Elevation of liver enzymes was an initial concern regarding the use of this new drug, which is not available for general use. Ongoing pharmacological research and future clinical trials may one day leave the "warfarin days" behind....

Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia A

“…Risk of atrial fibrillation (AF), the most common arrhythmia, increases with age and occurs in 6–8% of individuals above the eighth decade of life [1,2]. AF is classified as paroxysmal (paroxysmal atrial fibrillation, PAF), persistent or permanent based on timing and duration of episodes.…”

“…Cardioversion is used for persistent AF. Radiofrequency ablation (RFA) of ectopic electrical foci in the vicinity of the pulmonary veins may be offered to patients with PAF who have failed medical therapy [1–4].…”

Stroke and Dementia in Atrial Fibrillation

“…Antithrombotic agents such as aspirin or clopidogrel are not widely used, despite proven clopidogrel's greater efficacy, while the two combined in the ACTIVE study caused its premature cessation due to increased number of vascular events incidence. (Ali et al, 2006) Most promising therapeutic agents today seem to be direct thrombin inhibitors (ximelagatran, argatroban and dabigatran) that appear to be at least as effective as warfarine, but require no monitoring while having great bioavailability. (Spinler, 2010) …”

Edoxaban

“…[10] For example, in clinical practice, <60% of patients with AF who do not have contraindications to warfarin therapy are actually receiving it, and less than half of those are consistently within therapeutic targets. [10][11][12][13][14][15][16][17] As a consequence, warfarin is under-prescribed in clinical practice for stroke prevention in AF.…”