Clinical Significance of Non-Vitamin K Antagonist Oral Anticoagulants in the Management of Atrial Fibrillation

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp mation, described 150 years ago by Rudolph Virchow, 6 are present in AF. In fact, AF is often characterized by endocardial damage, from dilatation of the atria, 7 blood slowdown and stasis, 8 related to the anatomy of the atria, and abnormal changes in blood constituents, including platelet activation, 9 as well as inflammation 10 and changes in growth factor. 11 For these reasons, AF can favor a prothrombotic and hypercoagulable state. Warfarin, a VKA, is the most commonly used agent among the OACs used for thromboembolic prophylaxis in AF patients. Its effectiveness is proven by 64% relative risk reduction of stroke compared with placebo, 12 and it also shows superior results to aspirin 13 and to aspirin plus clopidogrel. 14 However, VKAs have some faults: (a) it takes time (days) to achieve a satisfactory therapeutic effect; (b) intricate superimposition with parenteral anticoagulants; (c) narrow therapeutic window; (d) significant interaction with several drugs and food, making regular monitoring of the therapeutic effect obligatory. For these reasons, a review found that up to 65% of patients at risk were not taking OACs, and the international normalized ratio (INR) was out of range in a further 19% of patients. 15 Thus, the impetus for the development of the nonvitamin K antagonist oral anticoagulants (NOACs), such as espite recent improvements in pharmacologic and electrical therapies, atrial fibrillation (AF) still remains the most common supraventricular tachyarrhythmia encountered in daily clinical practice. It affects 1-2% of the general population and its incidence increases in older patients. 1 The disease is frequently asymptomatic, but associated with a 2-fold increase in mortality, a 3-fold increase in congestive heart failure and a 5-fold increase in the risk of thromboembolic events, leading to frequent hospitalizations and worsened quality of life. 2 Although the use of antiarrhythmic medications leads to a significant improvement in symptoms, 3 assessment of thromboembolic risk and the use of adequate anticoagulation is mandatory in the proper therapeutic management of AF. 4,5 Physiopathology of Thromboembolism and Anticoagulants in AFThe association between AF and thromboembolic risk is widely recognized and the genesis of thrombus formation in AF is multifactorial. All the anatomical and physiopathological features of the triad of events necessary for thrombus for- Atrial fibrillation (AF) is the most commonly observed rhythm disorder in clinical practice. It is associated with a high risk of thromboembolic stroke and increased cardiovascular mortality. Vitamin K antagonists (VKAs), the only oral anticoagulants used for thromboembolic prophylaxis in AF patients over the past 60 years, have been effective in reducing thromboembolic stroke, compared with placebo and aspirin, in this group of patients. However, VKAs have a very narrow therapeutic window, so regular monitoring of the therapeutic ef...

Should We Maintain Anticoagulation after Successful Radiofrequency Catheter Ablation of Atrial Fibrillation? The Need for a Randomized Study

“…At the same time, radiofrequency catheter ablation (RFCA) seems to be very effective for the treatment of AF, showing a success rate ranging from 79.7 to 88.6% for paroxysmal AF and from 66.1 to 80% for the persistent form ( 7 ). Although the indication for anticoagulation therapy in AF patients is based on their thromboembolic risk ( 8 – 11 ), it is not clear what the correct behavior regarding anticoagulation management in AF patients undergoing a successful RFCA should be. Current guidelines recommend life-long extension of OAT even after successful RFCA in case of high thromboembolic risk, while no clear recommendations are provided for patients at low thromboembolic risk ( 4 – 6 ).…”

Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial

“…According to current guidelines [ 2 , 9 , 41 – 44 ], it is recommended that patients randomised to catheter ablation remain on uninterrupted warfarin treatment unless a different strategy is outlined by the operator. If patients are treated with novel oral anticoagulants (NOACs), they can be converted to warfarin treatment for 4 weeks before the catheter ablation procedure, continue with NOACs or stop the therapy 24–36 h before the ablation procedure, depending on the type of NOAC and clinician’s preference.…”

Decision Algorithms for Direct Oral Anticoagulant Use in Patients With Nonvalvular Atrial Fibrillation: A Practical Guide for Neurologists

“…All DOACs are substrates of P-glycoprotein (P-gp) and are metabolized by cytochrome P450 3A4 (CYP3A4) to varying degrees, with dabigatran and edoxaban having the lowest metabolic dependence on CYP3A4. 15 Concomitant use of P-gp or CYP3A4 modulators may alter DOAC exposure: P-gp or CYP3A4 inducers decrease DOAC exposure and thereby increase the risk of venous thromboembolism, while P-gp or CYP3A4 inhibitors generally increase DOAC exposure and may lead to increased bleeding risk. The effect of drug-drug interactions on DOAC exposure varies across the DOACs.…”