Is Bleeding a Necessary Evil?

The Inherent Risk of Antithrombotic Pharmacotherapy Used for Stroke Prevention in Atrial Fibrillation

Aung Myat; Yousif Ahmad; Shouvik Haldar; Udaya S Tantry; Simon R Redwood; Paul A Gurbel; Gregory YH Lip

Disclosures

Expert Rev Cardiovasc Ther. 2013;11(8):1029-1049. 

In This Article

Abstract and Introduction

Abstract

Current European atrial fibrillation (AF) guidelines have assigned a strong recommendation for the initiation of antithrombotic therapy to prevent thromboembolism in all but those AF patients at low risk (or with contraindications). Furthermore, the selection of antithrombotic therapy is based on the absolute risks of thromboembolism and bleeding, and the relative risk and benefit for a given patient. By their very mechanism of action, antithrombotic agents used for stroke prevention in AF will potentially increase the risk of bleeding events. Moreover, the introduction of novel oral anticoagulation agents have introduced new, hitherto ill-defined, deficiencies in the authors' knowledge with respect to anticoagulation monitoring, availability of direct antidotes, drug–drug interactions and the ability to appropriately control and reverse their actions if bleeding events occur. The authors present a comprehensive review on all aspects of bleeding related to currently licensed antithrombotic agents used for stroke prevention in patients with AF.

Introduction

Numerous longitudinal studies have demonstrated a higher incidence of heart failure exacerbations, hospitalizations and most importantly catastrophic stroke associated with atrial fibrillation (AF).[1] AF predisposes patients to a fivefold increased propensity for ischemic stroke and almost 20% of all ischemic strokes can be attributed to AF.[2,3] The risk of stroke during AF increases with age, with 6% in patients aged >65 years rising to 9% in 80–89 years compared with <1% prevalence in the general population.[3,4] A meta-analysis of stroke prevention in AF trials found an average stroke rate of 13% per year in untreated AF patients with prior stroke or transient ischemic attack (TIA) compared with 4.1% per year in AF patients with no history of stroke or TIA.[5] Strokes in AF patients are significantly more severe and are approximately twice as likely to result in a bedridden state and/or to be fatal (30-day mortality: odds ratio (OR) 1.84; 95% CI: 1.04–3.27) compared with non-AF-associated stroke.[6,7] The severity of stroke in AF also has a cost implication, the average direct cost of stroke in a patient with AF being significantly higher than in a patient without.[8]

It is clear that stroke protection is of fundamental importance in the management of AF patients. Current European AF guidelines have assigned a Class I (Level of Evidence A) recommendation for the initiation of antithrombotic therapy to prevent thromboembolism in all but those AF patients at low risk (i.e., <65 years and lone AF, or with contraindications).[9] Furthermore, it is recommended that the selection of antithrombotic therapy should be based on the absolute risks of stroke/thromboembolism and bleeding, and the relative risk and benefit for a given patient (Class I, Level of Evidence A).[9] By their very mechanism of action, antithrombotic agents used for stroke prevention in AF will potentially increase the risk of minor, major and catastrophic bleeding events. Moreover, the introduction of novel oral anticoagulation (NOAC) agents have also introduced some deficiencies in our knowledge with respect to anticoagulation monitoring, availability of direct antidotes, drug–drug interactions and the ability to appropriately control and reverse their actions if bleeding events occur.

In this review article, the authors present a comprehensive overview on all aspects of bleeding related to thromboprophylaxis for stroke prevention in AF in general, as well as a synopsis of all currently licensed antithrombotic agents for this indication.

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