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.

Prevalence and the factors associated with oral anticoagulant use among nursing home residents

“…Anticoagulants are widely used to prevent ischaemic stroke and other thrombotic events associated with conditions commonly afflicting older adults (eg atrial fibrillation, coronary artery disease, cancer and other hypercoagulable states) 1‐4 . Anticoagulants are also used for treatment of active thrombosis (eg venous thromboembolism) 5,6 .…”

Impact of heart failure on the clinical profile and outcomes in patients with atrial fibrillation treated with rivaroxaban. Data from the EMIR study

“…The concomitance of both conditions translates into higher morbidity and mortality rates, including a greater risk of thromboembolic events, and consequently, anticoagulation is recommended [6,[11][12][13]. Although a number of studies have analyzed the impact of HF on patients with AF taking vitamin K antagonists, the information currently available among patients treated with direct oral anticoagulants, particularly in clinical practice remains scarce [14][15][16][17][18].…”

Plasma Concentration and Pharmacodynamics of Edoxaban in Patients with Nonvalvular Atrial Fibrillation and Acute Heart Failure

“…Owing to the high frequency of thromboembolic complications, embolic prophylaxis with anticoagulants is required in patients with AF with heart failure [7]. It is reported that heart failure is associated with a hypercoagulable state as shown by the elevations of coagulation markers, thrombin/antithrombin complex, prothrombin fragment F1 + 2 (F1+2), and d-dimers [8].…”