title: Anticoagulation Therapy and NOACs in Heart Failure.
abstract: Current evidence indicates that heart failure (HF) confers a hyper-coagulable state that is associated with adverse events including stroke, systemic embolism, and mortality. This may be due to the elevated levels of pro-thrombotic and pro-inflammatory cytokines that are seen in patients with acute and chronic HF. Left ventricular wall motion abnormalities in patients with systolic dysfunction predispose to local thrombosis due to blood stasis as does atrial fibrillation (AF) which leads to blood stasis in regions of the atria. The high risk of thromboemboli in HF patients with AF has resulted in the use anticoagulation therapy to prevent the occurrence of catastrophic events. There is evidence, however, that the pro-inflammatory, pro-thrombotic state that exists in HF puts patients who are in sinus rhythm at risk. The novel oral anticoagulants (NOACs) have been shown in RCT to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding. The fact that the NOACs don't require routine monitoring to assure that patients remain within the therapeutic range and have relatively simple dosing requirements and a safer risk profile makes them attractive substitutes to warfarin in HF patients with atrial fibrillation and other conditions (e.g. deep venous thrombosis). Post hoc analyses from a subset of HF patients from the RCTs in AF patients have demonstrated similar findings as were reported in the entire populations that were included in the trials. As a result, NOACS are commonly used now in HF patients with AF. For HF patients with reduced ejection fraction in sinus rhythm, the use of warfarin in randomized clinical trials (RCT) to reduce stroke has been disappointing and associated with increase bleeding risk when compared to aspirin. The advantages of the NOACs over warfarin, however, raise the question of whether they might improve outcomes in HF patients who are in sinus rhythm. The currently ongoing COMMANDER-HF trial has been designed to address this issue. In this chapter we review evidence of existence of a prothombotic state in HF, the pharmacodynamics and clinical trials of the NOACs and the outcomes from NOAC substudies in the HF subgroup. We also discuss the rationale for using anticoagulation in HF independent of arrhythmia burden.
authors.affiliation: Cardiology Division, Department of Medicine, University of California, San Diego, 9444 Medical Center Drive, La Jolla, CA, 92034-7411, USA.
authors.forename: Isac
authors.initials: I
authors.lastname: Thomas
authors.affiliation: Cardiology Division, Department of Medicine, University of California, San Diego, 9444 Medical Center Drive, La Jolla, CA, 92034-7411, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: EncisoSilva
authors.affiliation: Cardiology Division, Department of Medicine, University of California, San Diego, 9444 Medical Center Drive, La Jolla, CA, 92034-7411, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Schlueter
authors.affiliation: Cardiology Division, Department of Medicine, University of California, San Diego, 9444 Medical Center Drive, La Jolla, CA, 92034-7411, USA. bgreenberg@ucsd.edu.
authors.forename: Barry
authors.initials: B
authors.lastname: Greenberg
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D002986:Clinical Trials as Topic; D000069604:Dabigatran / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000627:therapeutic use; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013844:Thiazoles / Q000627:therapeutic use; D054556:Venous Thromboembolism / Q000150:complications / Q000188:drug therapy; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
keywords: Atrial fibrillation; Bleeding; Heart failure; Novel oral anticoagulant; Randomized clinical trials; Stroke; Thrombosis