Dabigatran, a direct thrombin inhibitor, in atrial fibrillation: Is it already time for a change in oral anticoagulation therapy?

Abstract

Atrial fibrillation (AF) is a common arrhythmia, and its prevalence increases with aging and the severity of heart disease. AF affects more than 2 million people in the US, and more than 4 million in Europe. It is expected that the age adjusted prevalence in US will excede 10 million people by the year 2050. [1][2][3][4][5] In the last decade, we were able to see the light shed by several trials that dealt with AF mechanisms and the appropriate management of AF patients. Clinical studies have focused mainly on the electrophysiological properties of the substrate in the atrial muscle during sinus rhythm and on the atrial electrical responses elicited by premature stimulation method.6-9 However, many fundamental aspects of this arrhythmia have been poorly understood until quite recently, and there are several features on the mechanisms of AF that makes it difficult to manage it properly. Increasing awareness of AF as a disease with possible fatal complications rather than as an acceptable alternative to sinus rhythm has led to search for clear arguments to support a certain strategy as a golden standard.There is no atrial contraction during AF, a situation that renders the pooled blood inside the atrium susceptible to develop thrombus formation particularly in the left atrium. AF increases the overall risk of stroke five-fold, and is associated with particularly severe strokes .10-12 About 76% of AF patients have a moderate to high risk of embolic complications, and they have also a significant risk factor for stroke recurrence. [13][14][15] It looks very clear that all the difficulties we have to face in finding proper answer to its therapeutic management. Vitamin K antagonist drugs, such as warfarin and acenocumarol, reduce the risk of AF-related stroke by about 70%. 4,16 They are the only oral antico agulants currently recommended for the prevention of stroke in patients with a moderate to high risk of stroke 15 These pharmacological agents produce their anticoagulant effect by preventing the g-carboxylation of the vitamin K-dependent coagulation factors prothrombin and Factors VII, IX, and X.17 Despite the good clinical results obtained with these oral anticoagulants that are far from being ideal [ Table 1], there are some inconvenient factors which make their conventional use difficult to implement and follow. There is a consistent suboptimal utilization of oral anticoagulation therapy. Warfarin is prescribed to only two thirds of appropriate candidates despite guidelines recommendations. 18 The narrow therapeutic window in the anticoagulation process makes it neccessary to monitor closely the prothrombin time. Insufficient

Impact of VKORC1, CYP2C9, CYP1A2, UGT1A1, and GGCX polymorphisms on warfarin maintenance dose: Exploring a new algorithm in South Chinese patients accept mechanical heart valve replacement

“…With the advent of new oral anticoagulants, warfarin has been gradually replaced by dabigatran or rivaroxaban in the treatment of atrial fibrillation, deep venous thrombosis, or PE. [36][37][38] For anticoagulation after mechanical valve replacement, warfarin is still the only anticoagulant with the most reliable effect. [39] Therefore, considering the differences and risks of individualized warfarin medications, genebased algorithm model is considered to be a faster, safer, and more economical method of systemic administration than fixed model.…”

Idarucizumab, a humanized monoclonal antibody fragment, for reversal of Dabigatran therapy for atrial fibrillation

“…Warfarin, however, has limitations, including multiple interactions with other drugs and foods, genetic variability in metabolism, delayed onset and offset, and the need for frequent monitoring and dose adjustments. Given the limitations of Warfarin, clinicians and clinical investigators have been interested in the development of newer oral anticoagulants [19][20][21]. Therefore, there have been studies investigating the efficacy and safety of these agents.…”