Role of rivaroxaban in the management of atrial fibrillation: insights from clinical practice.

© 2018 Vimalesvaran et al. This work is published and licensed by Dove Medical Press Limited.Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and it leads to significant morbidity and mortality, predominantly from ischemic stroke. Vitamin K antagonists, mainly warfarin, have been used for decades to prevent ischemic stroke in AF, but their use is limited due to interactions with food and other drugs, as well as the requirement for regular monitoring of the international normalized ratio. Rivaroxaban, a direct factor Xa inhibitor and the most commonly used non-vitamin K oral anticoagulant, avoids many of these challenges and is being prescribed with increasing frequency for stroke prevention in non-valvular AF. Randomized controlled trial (RCT) data from the ROCKET-AF(Rivaroxaban once daily oral direct Factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) trial have shown rivaroxaban to be non-inferior to warfarin in preventing ischemic stroke and systemic embolism and to have comparable overall bleeding rates. Applicability of the RCT data to real-world practice can sometimes be limited by complex clinical scenarios or multiple comorbidities not adequately represented in the trials. Available real-world evidence in non-valvular AF patients with comorbidities - including renal impairment, acute coronary syndrome, diabetes mellitus, malignancy, or old age - supports the use of rivaroxaban as safe and effective in preventing ischemic stroke in these subgroups, though with some important considerations required to reduce bleeding risk. Patient perspectives on rivaroxaban use are also considered. Real-world evidence indicates superior rates of drug adherence with rivaroxaban when compared with vitamin K antagonists and with alternative non-vitamin K oral anticoagulants - perhaps, in part, due to its once-daily dosing regimen. Furthermore, self-reported quality of life scores are highest among patients compliant with rivaroxaban therapy. The generally high levels of patient satisfaction with rivaroxaban therapy contribute to overall favorable clinical outcomes.Peer reviewedFinal Published versio

A fresh perspective on anticoagulant therapy in patients with cancer in the era of NOAC

Cancer is a condition associated with hypercoagulability requiring anticoagulant therapy. In recent years, oncological patients have been given heparin and vitamin K antagonists. Nowadays, non-vitamin K antagonist oral anticoagulants (NOAC) are becoming increasingly widely used. Based on the current state of knowledge, NOAC drugs can be used in anticoagulant treatment of cancer patients with caution, i.e. after assessing the bleeding risk and a risk-benefit analysis of anticoagulant therapy, as well as of the drug interactions between oncological drugs and the NOAC group

A review of the anticoagulant pesticide Pindone

A review of the use of pindone for rabbit control in Western Australia is timely due to increased public concern over the use of this toxin, and because non-target deaths of some native Australian animals have been known to occur following its use. Pindone is one of the first generation indandione anticoagulant rodenticides which were developed in the late 1940\u27 s. The toxicity of anticoagulants arises from their inhibition of vitamin K-dependent clotting factors in the blood. Thus therapeutic administration of vitamin K provides a reliable antidote against anticoagulant poisoning. Pindone is slow acting and works best with repeated small doses. Pindone also has insecticidal and fungicidal properties, and can act as a systemic insecticide (eg. fleas, lice and mosquitoes). The implications of the latter for the main vectors responsible for the transmission of myxomatosis are unknown.https://researchlibrary.agric.wa.gov.au/books/1010/thumbnail.jp

Anticoagulation therapy in the elderly with non-valvular atrial fibrillation: a double-edged sword

Prevalence of non-valvular atrial fibrillation is increasing over time. Particularly in elderly population, treatment strategies to reduce the rate of stroke are challenging and still represent an unsolved cultural question. Indeed, the risk of thromboembolism increases in the elderly in parallel with the risk of bleeding. The frequent coexistence of several morbidities, frailty syndrome, polypharmacy, chronic kidney disease and dementia strengthens the perception that risk-benefit ratio of anticoagulant therapy could be unfavorable, and explains why such treatment is underused in the elderly. Recently, the introduction of non-vitamin K oral anticoagulants (NOACs) has allowed us to overcome the large number of limitations imposed by the use of vitamin K antagonists. In this manuscript, the benefits of individual NOACs in comparison with warfarin in elderly patients are reviewed. Targeted studies on complex elderly patients are needed to test usefulness of a geriatric comprehensive assessment, besides the scores addressing risk of thromboembolic and hemorrhagic events. In the meantime, it is mandatory that use of anticoagulant therapy in most elderly people, currently excluded from randomized controlled trials, is prudent and responsible

Current clinician perspective on non-vitamin K antagonist oral anticoagulant use in challenging clinical cases.

OBJECTIVE: The evolution of non-vitamin K antagonist anticoagulants (NOACs) has changed the horizon of stroke prevention in atrial fibrillation (SPAF). All 4 NOACs have been tested against dose-adjusted warfarin in well-designed, pivotal, phase III, randomized, controlled trials (RCTs) and were approved by regulatory authorities for an SPAF indication. However, as traditional RCTs, these trials have important weaknesses, largely related to their complex structure and patient participation, which was limited by strict inclusion and extensive exclusion criteria. In the real world, however, clinicians are often faced with complex, multimorbid patients who are underrepresented in these RCTs. This article is based on a meeting report authored by 12 scientists studying atrial fibrillation (AF) in diverse ways who discussed the management of challenging AF cases that are underrepresented in pivotal NOAC trials. METHODS: An advisory board panel was convened to confer on management strategies for challenging AF cases. The article is derived from a summary of case presentations and the collaborative discussions at the meeting. CONCLUSION: This expert consensus of cardiologists aimed to define management strategies for challenging cases with patients who underrepresented in pivotal trials using case examples from their routine practice. Although strong evidence is lacking, exploratory subgroup analysis of phase III pivotal trials partially informs the management of these patients. Clinical trials with higher external validity are needed to clarify areas of uncertainty. The lack of clear evidence about complex AF cases has pushed clinicians to manage patients based on clinical experience, including rare situations of off-label prescriptions

Non-vitamin K Oral Anticoagulants in atrial fibrillation: where are we now?

atrial fibrillation, non-vitamin K oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, warfarinAtrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of this complication. Until recently, the vitamin K antagonists (VKAs, e.g. warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, obligatory regular laboratory control, which all made warfarin 'inconvenient' both for patients and clinicians. The limitations of VKAs led to development of new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, edoxaban). The NOACs avoid many of the VKA drawbacks. In this review we will focus on the current evidence justifying use of NOACs in non-valvular AF

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. METHODS: Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). RESULTS: Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA2DS2-VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA2DS2-VASc=0 and 69% and 87% for CHA2DS2-VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). CONCLUSIONS: Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement

Minor bleeding in patients with atrial fibrillation using a non-vitamin K antagonist oral anticoagulant

Aims: We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin K antagonist oral anticoagulant (NOAC) therapy.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis.Results: Overall rate of minor bleeds was 19.2 per 100 patient years of follow up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use).Limitation: This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting.Conclusion: Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding

Real-practice thromboprophylaxis in atrial fibrillation

This retrospective observational study was based on databases of the Local Health Authority of Treviso, Italy. It evaluated the prevalence and the effectiveness of oral anticoagulation treatment (OAT) for the management of nonvalvular atrial fibrillation (NVAF) in everyday clinical practice. Out of 6,138 NVAF patients, only 3,024 received Vitamin K antagonist (VKA). Potential barriers decreasing the probability of being treated with VKA were female sex, older age, antiplatelet treatment and history of bleeding. In addition, VKA-treatment was not in line with current ESC and AIAC guidelines, since the patients at high or low risk of stroke were under-or over-treated, resp. Among VKAtreated patients, 73 % of subjects were not at target with anticoagulation. OAT resulted to be effective in reducing stroke risk. However, stroke events were significantly influenced also by previous stroke or transient ischemic attack (hazard ratio, HR = 2.99, p < 0.001) and by previous bleeding events (HR = 1.60, p < 0.001)

Régi és új orális antikoagulánsok hazai alkalmazása pitvarfibrillációban | Old and new oral anticoagulants in the management of atrial fibrillation. Hungarian data

Absztrakt: Bevezetés: A pitvarfibrilláció kezelésében a régi és az új antikoagulánsok jelentősen csökkentik a stroke és mortalitás előfordulását. Célkitűzés: Annak felderítése, hogy az elmúlt időben a pitvarfibrillációt elszenvedő betegek milyen arányban kaptak hatásos stroke-profilaxist, és milyen volt ezeknek a betegeknek a gyógyszer-adherenciája. Módszer: Az OEP/NEAK adatbázisában szereplő, pitvarfibrillációt elszenvedő betegekre vonatkozó adatgyűjtés. A vizsgált időszak: 2010–2015. Azok a betegek kerültek beválogatásra, akiknek ez idő alatt legalább egyszer szerepelt az I48 BNO-kód a nyilvántartásában. Adherensnek tekintettük azokat a betegeket, akik legalább 80%-ban kiváltották a receptjeiket. Eredmények: Magyarországon 3% a pitvarfibrilláció prevalenciája. Az adott évben egészségügyi ellátásra kerülő, pitvarfibrilláló betegek mortalitása 7–10% közötti. A betegek egyharmada nem kap effektív stroke-profilaxis kezelést. A legutolsó, 2015. évet figyelembe véve az adherencia 55% volt a K-vitamin-antagonistát szedőknél, míg 69,7% a direkt antikoagulánst szedőknél. Következtetések: Az új orális antikoagulánsok bevezetésével javítható volt a betegek adherenciája, de még mindig magas az effektív stroke-profilaxisban nem részesülők aránya. Orv Hetil. 2017; 158(39): 1545–1549. | Abstract: Introduction: Despite a progress in the management of patients with atrial fibrillation this arrhythmia is one of the major causes of stroke, heart failure, sudden death and cardiovascular morbidity. Oral anticoagulation with vitamin K antagonist or non-vitamin K antagonist markedly reduces stroke and mortality in atrial fibrillation patients. Aim: To estimate the real-life vitamin K antagonist and non-vitamin K antagonist oral anticoagulant treatment in past years in Hungary. Method: Analysis of the National Health Insurance Administation database for atrial fibrillation (BNO: I48) between 2010–2015. We assumed that AF patient would turn to health care provides at least once either as inpatients or outpatients in a 5-year period. The patient was accepted as adherent after 6 months therapy and at least 80% oral anticoagulant prescription. Results: The prevalence of AF in Hungary is 3%. The mortality rate of AF 7%–10% per year. The adherence of the old oral anticoagulant treatment was 55%, but it was 69% among patient treated by “new” oral anticoagulant treatment. However, one third of the patients are not treated by effective old or new oral anticoagulant treatment. Conclusions: We need more effort to improve the effective and high adherence oral anticoagulant therapy in our country. Orv Hetil. 2017; 158(39): 1545–1549