Major Outcomes in Atrial Fibrillation Patients with One Risk Factor: Impact of Time in Therapeutic Range

BACKGROUND: The benefits and harms of oral anticoagulation (OAC) therapy in patients with only one stroke risk factor (i.e. CHA2DS2-VASc= 1 in males, or 2 in females) has been subject of debate. METHODS: We analysed all patients with only one stroke risk factor from the merged datasets of SPORTIF III and V trials. Anticoagulation control was defined according to time in therapeutic range (TTR). RESULTS: Of the original trial cohort, 1,097 patients had only one stroke risk factor. Stroke/systemic thromboembolic event had an incidence of 0.9 per 100 patient-years, with an incidence of 1.6 per 100 patient-years for all-cause death and 2.3%/patient-years for the composite outcome of stroke/systemic thromboembolic event/all-cause death. There were no significant differences in the risk for stroke/systemic thromboembolic event between sexes, nor between the different stroke risk factors amongst these atrial fibrillation patients with only one stroke risk factor. Cox regression analysis in patients treated with warfarin only found TTR to be inversely associated with stroke/systemic thromboembolic event (p=0.034) and all-cause death (p=0.015). Chronic heart failure was significantly associated with the outcome of all-cause death (p=0.0019) and the composite outcome of stroke/systemic thromboembolic event/all-cause death (p=0.021). There was a significant inverse linear association between TTR and the cumulative risk for both stroke/systemic thromboembolic event and all-cause death (both p<0.001). CONCLUSIONS: In atrial fibrillation patients with only one additional stroke risk factor (i.e. CHA2DS2-VASc= 1 in males or 2 in females), rates of major adverse events (stroke/systemic thromboembolic event, mortality) were high, despite anticoagulation. TTR in warfarin-treated patients was inversely associated with the occurrence of both stroke/systemic thromboembolic event and all-cause death

Apixaban Enhances Endogenous Fibrinolysis in Patients with Atrial Fibrillation

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.AIMS: Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591-2300) vs. 2758 (2014-3502) vs. 2135 (1752-2463) s, P < 0.0001]. Among TEG indices, a small but significant difference in clot lysis time (CLT) was observed [apixaban 60.0 (45.0-61.0) vs. warfarin 61.0 (57.0-62.0) vs. aspirin 61.0 (59.0-61.0) min, P = 0.036]. Apixaban improved endogenous fibrinolysis measured using the GTT [LT pre-treatment 2204 (1779-2738) vs. on-treatment 1882 (1607-2374) s, P = 0.0003], but not by using TEG. Change in LT (ΔLT) with apixaban correlated with baseline LT (r = 0.77, P < 0.0001). There was weak correlation between ΔLT and ΔCLT in response to apixaban (r = 0.28, P = 0.02) and between on-apixaban LT and CLT (r = 0.25, P = 0.022). CONCLUSION: Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study.Peer reviewedFinal Accepted Versio

Reviews Can We Predict Stroke in Atrial Fibrillation?

Stroke prevention with appropriate thromboprophylaxis still remains central to the management of atrial fibrillation (AF). Nonetheless, stroke risk in AF is not homogeneous, but despite stroke risk in AF being a continuum, prior stroke risk stratification schema have been used to &apos;artificially&apos; categorise patients into low, moderate and high risk stroke strata, so that the patients at highest risk can be identified for warfarin therapy. Data from recent large cohort studies show that by being more inclusive, rather than exclusive, of common stroke risk factors in the assessment of the risk for stroke and thromboembolism in AF patients, we can be so much better in assessing stroke risk, and in optimising thromboprophylaxis with the resultant reduction in stroke and mortality. Thus, there has been a recent paradigm shift towards getting better at identifying the &apos;truly low risk&apos; patients with AF who do not even need antithrombotic therapy, whilst those with one or more stroke risk factors can be treated with oral anticoagulation, whether as well-controlled warfarin or one or the new oral anticoagulant drugs. The new European guidelines on AF have evolved to deemphasise the artificial low/moderate/high risk strata (as they were not very predictive of thromboembolism, anyway) and stressed a risk factor based approach (within the CHA 2 DS 2 -VASc score) given that stroke risk is a continuum. Those categorised as &apos;low risk&apos; using the CHA 2 DS 2 -VASc score are &apos;truly low risk&apos; for thromboembolism, and the CHA 2 DS 2 -VASc score performs as good as-and possibly better--than the CHADS 2 score in predicting those at &apos;high risk&apos;. Indeed, those patients with a CHA 2 DS 2 -VASc score = 0 are &apos;truly low risk&apos; so that no antithrombotic therapy is preferred, whilst in those with a CHA 2 DS 2 -VASc score of 1 or more, oral anticoagulation is recommended or preferred. Given that guidelines should be applicable for &gt;80% of the time, for &gt;80% of the patients, this stroke risk assessment approach covers the majority of the patients we commonly seen in everyday clinical practice, and considers the common stroke risk factors seen in these patients. The European guidelines also do stress that antithrombotic therapy is necessary in all patients with AF unless they are age &lt;65 years and truly low risk. Indeed, some patients with &apos;female gender&apos; only as a single risk factor (but still CHA 2 DS 2 -VASc score of 1, due to gender) do not need anticoagulation, especially if they fulfil the criterion of &apos;&apos;age &lt;65 and lone AF, and very low risk&apos;&apos;. In the European and Canadian guidelines, bleeding risk assessment is also emphasised, and the simple validated HAS-BLED score is recommended. A HAS-BLED score of ≥3 represents a sufficiently high risk such that caution and/or regular review of a patient is needed. It also makes the clinician think of correctable common bleeding risk factors, and the availability of such a score allows an informed assessment of bleeding risk in AF patients, when antithrombotic therapy is being initiated

Controversies and challenges of anticoagulation therapy in obesity

INTRODUCTION: The relationship between anticoagulation efficacy and safety in obesity is complex and can vary between degrees of obesity and anticoagulant choice. Indeed, patients at extremes of body weight were under-represented in randomized trials. Additionally, the possibility of an 'obesity paradox' has been raised in atrial fibrillation, describing decreased thromboembolic risk in obese patients.AREAS COVERED: We explore the current literature on anticoagulation in obesity, specifically with regard to efficacy in atrial fibrillation, efficacy in venous thromboembolism, and bleeding risk. Pharmacodynamic and pharmacokinetic considerations are also discussed.EXPERT OPINION: As a class, direct oral anticoagulants are comparable to vitamin-K antagonists in preventing and treating thromboembolism in overweight and obese patients, whilst not increasing bleeding risk.</p