Haemorrhagic complications following cataract and vitreoretinal surgery with sub-Tenon's block in patients receiving non-vitamin K oral anticoagulant agents: A prospective audit.

There is a lack of data to support either continuation or interruption of non-vitamin K oral anticoagulants for cataract and vitreoretinal surgery. A prospective audit was undertaken of 291 patients undergoing cataract surgery or vitreoretinal surgery, predominantly under sub-Tenon's block, while continuing these agents. The median time from last non-vitamin K oral anticoagulant dose to the insertion of sub-Tenon's block was five hours. No patient required emergency reversal of anticoagulation. There were no sight-threatening complications in the immediate perioperative period, although two vitreoretinal patients (3.8%) had a moderate haemorrhagic complication on day five, and two cataract patients (0.8%) had a minor haemorrhagic complication on days one and 14 postoperatively. Despite continuing their non-vitamin K oral anticoagulants, three (1%) cataract patients had a moderate thromboembolic complication within the 30-day postoperative period. The risk of haemorrhagic complications associated with continuation of anticoagulation with non-vitamin K oral anticoagulants for cataract and vitreoretinal surgery is low, and this audit supports the continuation of non-vitamin K oral anticoagulants for our patients having cataract and vitreoretinal surgery.

An emulated target trial analysis based on Medicare data suggested non-inferiority of Dabigatran versus Rivaroxaban.

OBJECTIVES: Rivaroxaban and Dabigatran were the first two non-vitamin K antagonist oral anticoagulants (NOACs) for preventing stroke among non-valvular Atrial Fibrillation patients. This article aimed to evaluate the relative efficacy and safety of Rivaroxaban versus Dabigatran. STUDY DESIGN AND SETTING: An emulated target trial analysis was conducted based on Medicare, in which we constructed three "randomized clinical trials" with well-defined inclusion/exclusion criteria, treatment regimens, and analysis procedures. We analyzed the individual trials, examined temporal variations, and generated unified results via pooled analysis. RESULTS: With a two-year data collection window (2012-2013), 70,129 subjects were enrolled in the three emulated trials, with 36,269 and 34,089 in the Rivaroxaban and Dabigatran arms, respectively. Dabigatran (the reference group for hazard ratio - HR) was superior regarding time to any primary event (including ischemic stroke, other thromboembolic events, major bleeding, and death; HR 1.232, P-value 0.0025), major bleeding (HR 1.187, P-value <0.0001), and mortality (HR 1.488, P-value <0.0001). Differences regarding stroke and other thromboembolic events were not significant. CONCLUSION: Dabigatran was found as superior for the Medicare patients with multiple chronic conditions. Temporal variations, which had been largely neglected in the literature, were observed. This study may provide new insight into treating AF with NOACs.

Off-target effects of oral anticoagulants - vascular effects of vitamin K antagonist and non-vitamin K antagonist oral anticoagulant dabigatran etexilate.

INTRODUCTION: Vitamin K antagonists (VKA) and non-vitamin K oral antagonist anticoagulants (NOAC) are used in the clinic to reduce risk of thrombosis. However, they also exhibit vascular off-target effects. The aim of this study is to compare VKA and NOAC on atherosclerosis progression and calcification in an experimental setup. MATERIAL AND METHODS: Female Apoe-/- mice (age 12 weeks) were fed Western-type diet as control or supplemented with dabigatran etexilate or warfarin for 6 or 18 weeks. Vascular calcification was measured in whole aortic arches using µCT and [18 F]-NaF. Atherosclerotic burden was assessed by (immuno)histochemistry. Additionally, in vitro effects of warfarin, thrombin, and dabigatran on primary vascular smooth muscle cells (VSMC) were assessed. RESULTS: Short-term treatment with warfarin promoted formation of atherosclerotic lesions with a pro-inflammatory phenotype, and more rapid plaque progression compared with control and dabigatran. In contrast, dabigatran significantly reduced plaque progression compared with control. Long-term warfarin treatment significantly increased both presence and activity of plaque calcification compared with control and dabigatran. Calcification induced by warfarin treatment was accompanied by increased presence of uncarboxylated matrix Gla protein. In vitro, both warfarin and thrombin significantly increased VSMC oxidative stress and extracellular vesicle release, which was prevented by dabigatran. CONCLUSION: Warfarin aggravates atherosclerotic disease activity, increasing plaque inflammation, active calcification, and plaque progression. Dabigatran lacks undesired vascular side effects and reveals beneficial effects on atherosclerosis progression and calcification. The choice of anticoagulation impacts atherosclerotic disease by differential off target effect. Future clinical studies should test whether this beneficial effect also applies to patients.

5-year outcomes from rivaroxaban therapy in atrial fibrillation: Results from the Dresden NOAC Registry.

INTRODUCTION: Following successful phase-III trials, direct oral anticoagulants such as rivaroxaban have largely replaced warfarin for stroke prevention in atrial fibrillation (SPAF). However, data from randomized trials should be confirmed in unselected cohorts. MATERIALS AND METHODS: Prospective registries can provide such data but often limit follow-up to short periods only. Extending our previously reported follow-up of 2.2 years in 1204 SPAF patients receiving rivaroxaban in the non-interventional DRESDEN NOAC REGISTRY, we now provide prospectively collected 5 years data (mean follow-up 5.5 ± 2.3 years) for this cohort. RESULTS: Between 1 October 2011 and 31 December 2019, the combined endpoint of stroke/transient ischemic attack/systemic embolism occurred at a rate of 2.3/100 patient-years in the intention-to-treat analysis (95% confidence interval [CI] 1.9-2.7) and at 1.6/100 patient-years in the on-treatment analysis (events within 3 days after last drug intake). On-treatment rates for major or clinically relevant non-major bleeding were 3.1 and 19.6/100 patient-years, respectively. Rivaroxaban treatment discontinuation occurred in a total of 574 patients during follow-up (11.0/100 patient-years in Kaplan-Meier analysis) and 426 patient died (all-cause mortality 6.3/100 pt. years; mean time from enrolment 3.6 ± 2.1 years), of which the causes of death were reported as arterial or venous embolism for 32 patients (21 occurring after treatment discontinuation and 11 during active treatment) and as bleeding for 24 patients. CONCLUSIONS: Our data provide reassuring long-term outcome data for an elderly, co-morbid SPAF population, especially with regard to the low rate of fatal thromboembolic and bleeding complications.

The Net Clinical Benefit of Rivaroxaban Compared to Low-Molecular-Weight Heparin in the Treatment of Cancer-Associated Thrombosis: Systematic Review and Meta-Analysis.

Cancer-associated thrombosis (CAT) carries significant morbidity and mortality. Low-molecular-weight heparin (LMWH) remains the standard of care, with recent systematic studies suggesting the efficacy and safety of rivaroxaban in the treatment of CAT. Uncertainty, however, remains regarding rivaroxaban efficacy and safety in real-world settings. We performed a systematic review and meta-analysis of studies comparing rivaroxaban to LMWH. We searched PubMed, MEDLINE, and EMBASE. The primary outcome was the net clinical benefit (NCB), while rates of major bleeding (MB), venous thromboembolism (VTE), clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality events were secondary outcomes. Seventeen studies were included in the final analysis. Rivaroxaban had a better NCB (relative risk [RR] = 0.82; 95% CI = 0.75-0.89, Q = 10.51, I 2 = 0%), less VTE events (RR = 0.73, 95% CI = 0.65-0.82, Q = 6.76, I 2 = 0%), and lower all-cause mortality (RR = 0.72, 95% CI = 0.57-0.91, Q = 32.8, I 2 = 79%) compared to LMWH. Additionally, comparable MB events (RR = 1.07, 95% CI = 0.85-1.33, Q = 16.9, I 2 = 11%). However, CRNMB events were higher in the rivaroxaban group (RR = 2.02, 95% CI = 1.46-2.80, Q = 9.9, I 2 = 19%). Additional analyses demonstrated consistency of results. Our review encompassing data from randomized and real-world data suggested rivaroxaban superiority compared to LMWH in terms of a better NCB, fewer VTE events, lower all-cause mortality, and comparable MB risk while carrying a higher risk of CRNMB. These findings support the use of rivaroxaban in the treatment of CAT. Additionally, it warrants a sizable randomized controlled study testing the superiority of rivaroxaban versus LMWH formulation and ascertaining bleeding outcomes according to cancer type and site.

Rivaroxaban compared to no treatment in ER-negative stage I-III early breast cancer patients (the TIP Trial): study protocol for a phase II preoperative window-of-opportunity study design randomised controlled trial.

BACKGROUND: Breast cancer patients are at a four-fold increased risk of developing a venous thromboembolism (VTE), a major cause of death in this group. Conversely, coagulation factors promote tumour growth and metastasis. This has been evidenced in preclinical models, with an inhibitory effect of anticoagulants on cancer growth through proliferative, angiogenic, apoptotic, cancer stem cell and metastatic processes. The extrinsic clotting pathway is also more upregulated in patients in the relatively poorer prognosis oestrogen receptor (ER)-negative breast cancer subgroup, with increased tumour stromal expression of the coagulation factors Tissue Factor and thrombin. Rivaroxaban (Xarelto®, Bayer AG, Leverkusen, Germany) is a direct oral anticoagulant (DOAC). It is a Factor Xa inhibitor that is routinely prescribed for the prevention of stroke in non-valvular atrial fibrillation and for both VTE prophylaxis and treatment. This trial will assess the anti-proliferative and other anti-cancer progression mechanisms of Rivaroxaban in ER-negative early breast cancer patients. METHODS: This UK-based preoperative window-of-opportunity phase II randomised control trial will randomise 88 treatment-naïve early breast cancer patients to receive 20 mg OD Rivaroxaban treatment for 11 to 17 days or no treatment. Treatment will be stopped 24 h (range 18-36 h) prior to surgery or repeat core biopsy. All patients will be followed up for 2 weeks following surgery or repeat core biopsy. The primary endpoint is change in tumour Ki67. Secondary outcome measures include tumour markers of apoptosis and angiogenesis, extrinsic clotting pathway activation and systemic markers of metastasis, tumour load and coagulation. DISCUSSION: Laboratory evidence supports an anti-cancer role for anticoagulants; however, this has failed to translate into survival benefit when trialled in patients with metastatic disease or poor prognosis cancers, such as lung cancer. Subgroup analysis supported a potential survival benefit in better prognosis advanced disease patients. This is the first study to investigate the anti-cancer effects of anticoagulants in early breast cancer. TRIAL REGISTRATION: UK National Research Ethics Service (NRES) approval 15/NW/0406, MHRA Clinical Trials Authorisation 48380/0003/001-0001. The sponsor is Manchester University NHS Foundation Trust, and the trial is co-ordinated by Cancer Research UK Liverpool Cancer Trials Unit (LCTU). EudraCT 2014-004909-33 , registered 27 July 2015. ISRCTN14785273 .

Profile of Patients Diagnosed With Acute Venous Thromboembolism in Routine Clinical Practice: The RE-COVERY DVT/PE™ Study.

BACKGROUND: The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions. METHODS: In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later. RESULTS: A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke. CONCLUSIONS: These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Novel Perspective for Antithrombotic Therapy in TAVI.

While surgical aortic valve replacement (SAVR) was for years the only available treatment for symptomatic aortic stenosis, the introduction of transcatheter aortic valve implantation (TAVI) in 2002 and the improvement of its technical aspects in the following years, has holistically changed the synchronous therapeutic approach of aortic valve stenosis. Recent evidence has expanded the indication of TAVI from high to lower surgical risk populations with symptomatic aortic stenosis. The administration of antithrombotic therapy periprocedurally and its maintenance after a successful TAVI is crucial for the prevention of complications and affects postprocedural survival. Randomized controlled trials investigating the appropriate combination and the duration of antithrombotic treatment after TAVI are for the moment scarce. This review article sheds light on the underlying pathogenetic mechanisms contributing in periprocedural TAVI thrombotic complications and discuss the efficacy of current antithrombotic policies as evaluated in randomized trials.

Trends in anticoagulant prescribing: a review of local policies in English primary care.

BACKGROUND: Oral anticoagulants are prescribed for stroke prophylaxis in patients with atrial fibrillation, which is the most common heart arrhythmia worldwide. The vitamin K antagonist (VKA) warfarin is a long-established anticoagulant. However, newer direct oral anticoagulants (DOACs) have been recently introduced as an alternative. Given the prevalence of atrial fibrillation, anticoagulant choice has substantial clinical and financial implications for healthcare systems. In this study, we explore trends and geographic variation in anticoagulant prescribing in English primary care. Because national guidelines in England do not specify a first-line anticoagulant, we investigate the association between local policies and prescribing data. METHODS: Primary care prescribing data of anticoagulants for all NHS practices from 2014 to 2019 in England was obtained from the ePACT2 database. Public formularies were accessed online to obtain local anticoagulation prescribing policies for 89.5% of clinical commissioning groups (CCGs). These were categorized according to their recommendations: no local policies, warfarin as first-line, or identification of a preferred DOAC (but not a preferred anticoagulant). Local policies were cross-tabulated with pooled prescribing data to measure the strength of association with Cramér's V. RESULTS: Nationally, prescribing of DOACs increased from 9% of all anticoagulants in 2014 to 74% in 2019, while that of warfarin declined accordingly. Still, there was significant local variation. Across geographical regions, DOACs ranged from 53 to 99% of all anticoagulants. Most CCGs (73%) did not specify a first-line choice, and 16% recommended warfarin first line. Only 11% designated a preferred DOAC. Policies with a preferred DOAC indeed correlated with increased prescribing of that DOAC (Cramér's V = 0.25, 0.27, 0.38 for rivaroxaban, apixaban, edoxaban respectively). However, local policies showed a negligible relationship with the classes of anticoagulants prescribed-DOAC or VKA (Cramér's V = 0.01). CONCLUSIONS: Nationally, the use of DOACs to treat atrial fibrillation has increased rapidly. Despite this, significant geographical variation in uptake remains. This study provides insights on how local policies relate to this variation. Our findings suggest that, in the absence of a nationally recommended first-line anticoagulant, local prescribing policies may aid in deciding between individual DOACs, but not in adjudicating between DOACs and vitamin K antagonists (i.e. warfarin) as general classes.

Rivaroxaban Versus Warfarin for Stroke Prevention and Venous Thromboembolism Treatment in Extreme Obesity and High Body Weight.

Background: Limited clinical data exist describing the use of direct-acting oral anticoagulants (DOACs) in patients with body mass index (BMI) >40 kg/m2 or body weight >120 kg. Thus, DOAC therapy in this population remains controversial. Objectives: To investigate rivaroxaban as a safe and effective alternative to warfarin for venous thromboembolism (VTE) treatment and prevention of stroke in patients with atrial fibrillation identified as extremely obese or of high body weight. Methods: A retrospective chart review was performed at 2 academic medical centers in patients ≥18 years old and BMI >40 kg/m2 or weight >120 kg, newly initiated on warfarin or rivaroxaban for atrial fibrillation or VTE treatment. The primary end point was incidence of clinical failure, defined as VTE recurrence, stroke incidence, and mortality, within 12 months of initiation. Secondary end points included length of stay (LOS) and bleeding complications. Results: A total of 176 patients were included, with 84 and 92 patients in the rivaroxaban and warfarin arms, respectively. Clinical failure was lower in the rivaroxaban group but did not reach statistical significance when compared with warfarin (5% vs 13%; P = 0.06). LOS was significantly shorter in the rivaroxaban arm (2 days [1-3] vs 4 days [2-7], P < 0.0001). Percentage of bleeding complications was higher in the rivaroxaban arm but not statistically significant (8% vs 2%, P = 0.06). Conclusion and Relevance: Although not statistically significant, rivaroxaban trended toward a lower incidence of clinical failure while demonstrating a significantly shorter LOS when compared with warfarin for VTE treatment or atrial fibrillation in morbidly obese or high-body-weight patients.

Effect of antithrombotic drugs on bone health.

With the increasing consumption of antithrombotic drugs among old people, expected as well as unexpected side effects on bone health are considerable, e.g. osteoporosis, fragility fractures, etc. This review focuses on antithrombotic drugs and their effects on bone health. The following groups were reviewed: parenteral long-term use of unfractionated heparin (UFH) is associated with osteopenia. The oral intake of vitamin K antagonists (VKA) makes them more convenient than UFH but chronic use also results in osteopenia. Limited reports of bone loss have been associated with low molecular weight heparins (LMWH) and indirect factor Xa inhibitors but in contrast to VKA and UFH they are less associated with osteopenia. There have been limited studies evaluating the effect of new oral anticoagulants (NOACs) on bones. Overall, they are considered safer than other drugs. There have been no reports about acetylsalicylic acid (ASA) and clopidogrel causing osteopenia but their metabolism by the kidneys and liver can cause reduced 25-hydroxy-vitamin D levels and can theoretically contribute to osteoporosis. Some reports suggested that high dosage clopidogrel can also negatively affect bones. After a detailed literature review long-term use of antithrombotic drugs can negatively affect the bones. Their role in bone health needs to be studied in detail and the clinical use in geriatric patients should be prudent.

Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome.

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of Very Low Dose Rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals. The VaLiDate-R study (ClinicalTrials.gov Identifier: NCT03775746, EudraCT: 2018-003299-11) is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time > 2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test. If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.

Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement.

There is a high degree of uncertainty regarding optimum care of patients with potential or known intake of oral anticoagulants and traumatic brain injury (TBI). Anticoagulation therapy aggravates the risk of intracerebral hemorrhage but, on the other hand, patients take anticoagulants because of an underlying prothrombotic risk, and this could be increased following trauma. Treatment decisions must be taken with due consideration of both these risks. An interdisciplinary group of Austrian experts was convened to develop recommendations for best clinical practice. The aim was to provide pragmatic, clear, and easy-to-follow clinical guidance for coagulation management in adult patients with TBI and potential or known intake of platelet inhibitors, vitamin K antagonists, or non-vitamin K antagonist oral anticoagulants. Diagnosis, coagulation testing, and reversal of anticoagulation were considered as key steps upon presentation. Post-trauma management (prophylaxis for thromboembolism and resumption of long-term anticoagulation therapy) was also explored. The lack of robust evidence on which to base treatment recommendations highlights the need for randomized controlled trials in this setting.

Is the prescription right? A review of non-vitamin K antagonist anticoagulant (NOAC) prescriptions in patients with non-valvular atrial fibrillation. Safe prescribing in atrial fibrillation and evaluation of non-vitamin K oral anticoagulants in stroke prevention (SAFE-NOACS) group.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are a major advance for stroke prevention in atrial fibrillation (AF). Use of the vitamin K antagonist (VKA), warfarin, has dropped 40% since 2010 in our institution. There is limited Irish hospital data on NOAC prescribing for stroke prevention. METHOD: Single centre, retrospective observational cohort study of consecutive AF patients at increased risk of stroke and/or awaiting electrical cardioversion. Data on prescribed NOACs from February 2010 till July 2015 was collected from the electronic inpatient record. Appropriateness of prescriptions was based on CHA2DS2-VASC score and accuracy on individual NOAC SPCs. Potential drug interactions and bleeding risk were also quantified. RESULTS: A total of 348 patients AF and increased risk of stroke (CHA2DS2-VASC score > 1 for men and > 2 for women) were studied. Forty-eight percent were female with a mean age 71 ± 18.6 years, 52% of whom were > 75. Mean CHA2DS2-Vasc and HAS-BLED scores were 4.1 ± 1.8 and 1.4 ± 0.8, respectively. Rivaroxaban, dabigatran and apixaban were prescribed to 154 (54.2%), 106 (34.3%) and 41 (13.2%) patients, respectively. 20.4% had inaccurate prescriptions; 92.9% (n = 65) underdosed and 7.1% (n = 5) on inappropriately higher doses. Neither choice of NOAC, age, history of anaemia, previous bleeding or co-prescribed antiplatelets influenced the accuracy of prescription (p = NS), but decreased renal function appeared to do so (p = 0.05). CONCLUSION: Our study highlights significant inaccuracies in NOAC prescribing. Patients commenced on NOACs should be assessed and followed up in a multidisciplinary AF clinic to ensure safe and effective prescribing and stroke prevention.

[The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease]. / Der multimorbide Patient: Einsatz neuer oraler Antikoagulanzien bei Patienten mit chronischer Niereninsuffizienz.

The Multimorbid Patient: Use of New Oral Anticoagulants in Patients with Chronic Kidney Disease Abstract. Increasing life expectancy in Western countries is associated with a high prevalence of multiple chronic diseases which is defined by the term "multimorbidity". Many of these patients suffer from chronic kidney disease (CKD) and thrombogenic comorbidities such as atrial fibrillation with the need for oral anticoagulation. For decades vitamin K antagonists have been exclusively prescribed for oral anticoagulation. However, due to altered pharmacokinetics and bioavailability of these drugs in CKD, a significant risk of bleeding exists. The introduction of direct oral anticoagulants as a new and promising alternative to vitamin K antagonists was -especially for CKD patients - highly anticipated. However, data from randomized studies are missing for older patients with advanced CKD. Consequently, a careful evaluation of the risk-benefit ratio is recommended for this sensitive patient population.

Non-Vitamin K-Dependent Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With CKD: Pragmatic Considerations for the Clinician.

Management of atrial fibrillation (AF) in patients with advanced chronic kidney disease (CKD) poses a complex conundrum because of higher risks for both thromboembolic and bleeding complications compared to the general population. This makes it particularly important for clinicians to carefully weigh the risks versus benefits of anticoagulation therapy to determine the individualized net clinical benefit for every patient. During the past few years, 4 non-vitamin K-dependent oral anticoagulant (NOAC) agents have supplemented warfarin in the therapeutic armamentarium for the prevention of systemic thromboembolism in nonvalvular AF. However, the use of NOACs in CKD specifically mandates a nuanced understanding due to their varying dependence on renal clearance, with resultant safety implications related to either underdosing (thromboembolism) or excessive drug exposure (bleeding). This pragmatic review highlights unique considerations pertaining to accurate estimation and temporal monitoring of kidney function in the context of NOAC use with specific clinical deliberations and variables when determining whether an NOAC is appropriate for a patient with CKD. The dependence of NOACs on renal clearance and several troubling safety signals in the published literature suggest that it is vital for nephrologists to be active members of a multidisciplinary team caring for these high-risk patients with CKD and AF.