Warfarin Use In Patients Research Articles

Clinical Impact of the Use of Warfarin in Patients with Atrial Fibrillation Undergoing Maintenance Hemodialysis.

Background: We evaluated the impact of warfarin use on the clinical outcomes of patients with atrial fibrillation who were undergoing hemodialysis (HD). Methods: A retrospective analysis was conducted utilizing data from patients undergoing maintenance HD who participated in HD quality assessment programs. Patients who were assigned the diagnostic code for atrial fibrillation (n = 4829) were included and divided into two groups based on the use of warfarin: No group (no warfarin prescriptions (n = 4009)), and Warfarin group (warfarin prescriptions (n = 820)). Results: Cox regression analyses revealed that the hazard ratio for all-cause mortality in the Warfarin group was 1.15 (p = 0.005) in univariate analysis and 1.11 (p = 0.047) in multivariable analysis compared to that of the No group. Hemorrhagic stroke was significantly associated with warfarin use, but no significant association between the use of warfarin and ischemic stroke or cardiovascular events was observed. The subgroup results demonstrated similar trends. Conclusions: Warfarin use is associated with a higher risk of all-cause mortality and hemorrhagic stroke, and has a neutral effect on ischemic stroke and cardiovascular events in patients with atrial fibrillation who are undergoing HD, compared to those who are not using warfarin.

Abdominal Aortic Aneurysm with Persistent and Rebound Coagulopathy Despite Aggressive Corrective Treatment: A Case Report

Abdominal aortic aneurysm (AAA) is not uncommon to cause coagulopathy. Warfarin use in patients presented with ruptured AAA can further complicate the preparation for surgical intervention and affect prognosis. We reported a case of impending rupture AAA that progressed to contained leak AAA in a warfarin user, with persistent elevated and rebound international normalized ratio (INR) despite aggressive correction with fresh frozen plasma (FFP) and three-factor prothrombin complex concentrate (3F-PCC). Persistent and rebound coagulopathy is possible in AAA. Corrective treatment with FFP or 3F-PCC alone does not always guarantee the successful reversal of coagulopathy in AAA. Some cases, especially those that failed the initial corrective treatment, require more aggressive reversal with co-administration of vitamin K. This case described coagulopathy in AAA, anticoagulation reversal agents used and emphasized the importance of rigorous coagulation profile monitoring in managing AAA.

Abstract 11251: Warfarin versus Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus; A Multicenter Retrospective Observational Study

Introduction: Left Ventricular (LV) thrombus formation is seen in some patients with severely reduced ejection fraction. Current guidelines recommend the use of warfarin in patients with LV thrombus. However, safe and effective warfarin use is often inconvenient and burdensome to some patients. Hypothesis: Direct oral anticoagulants (DOACs) are as effective as warfarin in the treatment of LV thrombus. Methods: We performed a multicenter retrospective analysis of adults admitted between January 2015 and December 2021 and diagnosed with LV thrombus. The primary outcome was thrombus resolution. Secondary outcomes included all-cause mortality, bleeding events and stroke or systemic embolism (SSE). Chi-square test was used to compare categorical variables. T-test was used for continuous variables comparison. Logistic regression was used to evaluate primary and secondary outcomes to control confounding factors such as demographic and comorbidity information. Results: A total of 194 patients were included, 48 (24.7%) of whom were treated with DOACs. The mean age was 61.6 ±13.3 years and 46 (23.7%) of the population were females. The two arms had no significant differences in age, sex, BMI, CHA2DS2-VASc score, history of DM, HTN, atrial fibrillation or ischemic cardiomyopathy. The rate of thrombus resolution (DOACs 58.3% vs warfarin 66.4%, p=0.309) and bleeding events (DOACs 14.6% vs warfarin 13.7%, p=0.878) were similar in both arms. The rate of SSE was numerically lower in the DOACs arm without statistical significance (DOACs 8.3% vs warfarin 15.07%, p=0.309). All-cause mortality was significantly higher in the DOACs arm (DOACs 22.9% vs warfarin 10.3%, p=0.026). In multivariate analysis, there was no significant effect of using warfarin on thrombus resolution, all-cause mortality, bleeding evens, and SSE (Figure). Conclusions: In our retrospective analysis, DOACs had similar efficacy and safety when compared to warfarin in the treatment of LV thrombus.

Association of Risk of Dementia With Direct Oral Anticoagulants Versus Warfarin Use in Patients With Non-valvular Atrial Fibrillation: A Systematic Review and Meta-analysis.

Atrial fibrillation (AF) is associated with an increased risk of dementia. Studies have shown the beneficial effects of anticoagulants in preventing dementia in this population. However, evidence around the use of direct oral anticoagulants (DOACs) versus warfarin in AF-related dementia prevention remains sparse. This systematic review and meta-analysis aimed to evaluate the use of DOACs versus warfarin in dementia prevention in this population. MEDLINE, EMBASE, PsycINFO, and the CENTRAL databases were systematically searched from its inception until May 2020. Nine studies (n = 611,069) were included for quantitative meta-analysis. DOACs use was associated with a lower risk of composite dementia outcomes compared with warfarin use [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.94, P = 0.03]. No significant difference was found in subtypes of dementia (vascular dementia, Alzheimer's disease, and cognitive disorder) between both groups. No significant difference in the risk of composite dementia outcomes between the dabigatran and warfarin groups (OR 0.97, 95% CI 0.88-1.08, P = 0.61). Apixaban (OR 0.58, 95% CI 0.50-0.67, P < 0.00001) and rivaroxaban (OR 0.67, 95% CI 0.61-0.75, P < 0.00001) use were both associated with a significantly lower risk of composite dementia outcomes compared with warfarin use. Findings need to be interpreted with caution because of low certainty of evidence. In conclusion, this systematic review and meta-analysis of 9 comparative studies demonstrated the superiority of DOACs over warfarin in prevention of dementia in AF. Future prospective trials with adequate follow-up period are warranted to ascertain its causal relationship.

Time in therapeutic range, quality of life and treatment satisfaction of patients on long-term warfarin for non-valvular atrial fibrillation: a cross-sectional study

BackgroundThe use of warfarin in patients with non-valvular atrial fibrillation (NVAF) can be challenging. In this study, we evaluate the time in therapeutic range (TTR), health-related quality of life (HRQoL) and treatment satisfaction of patients on long-term warfarin for NVAF. The HRQoL and treatment satisfaction were compared based on the TTR.MethodsA cross-sectional study was conducted among patients on warfarin for NVAF who attended the anticoagulant clinic of a tertiary cardiology referral center in Sarawak from 1st June 2018 to 31st May 2019. Patients’ TTR was calculated by using Rosendaal technique, while their HRQoL and treatment satisfaction were assessed by using Short Form 12 Health Survey version 2 (SF12v2) and Duke Anticoagulant Satisfaction Scale (DASS), respectively.ResultsA total of 300 patients were included, with mean TTR score of 47.0 ± 17.3%. The physical component summary (PCS) and mental component summary (MCS) score of SF-12v2 were 47.0 ± 9.0 and 53.5 ± 9.6, respectively. The total score for DASS was 55.2 ± 21.3, while the score for limitations (L), hassles and burdens (H&B) and positive psychological impacts (PPI) were 18.0 ± 10.0, 15.6 ± 9.1 and 21.6 ± 5.9, respectively. Seventy-three (24.3%) patients had good TTR (≥ 60%), with mean of 70.2 ± 8.7%; while 227 (75.5%) patients with poor TTR had significantly lower mean of 39.5 ± 11.9% (p = 0.006). There was no significant difference in the score of PCS (p = 0.150), MCS (p = 0.919) and each domain of SF-12v2 (p = 0.184–0.684) between good and poor TTR, except for social functioning (p = 0.019). The total DASS score was also not significantly different between group (p = 0.779). Similar non-significant difference was also reported in all the DASS sub dimensions (p = 0.502–0.699).ConclusionsMajority of the patients on long-term warfarin for NVAF in the current study have poor TTR. Their HRQoL and treatment satisfaction are independent of their TTR. Achieving a good TTR do not compromise the HRQoL and treatment satisfaction. Therefore, appropriate measures should be taken to optimise INR control, failing which direct oral anticoagulant therapy should be considered.

Evaluation of Warfarin Use in Patients With Mental Health Conditions in a Rural Community Health Center System.

Background: Mental health conditions (MHCs) may affect a patient's ability to comply with requirements necessary for safe warfarin use. Objective: To describe warfarin control, defined as time in therapeutic range (TTR), for patients with and without MHCs receiving care through a pharmacist-driven anticoagulation service within a rural community health center system. Methods: Retrospective cohort study of patients on warfarin between January 1, 2014, and December 31, 2017. The primary study endpoint was TTR. Secondary endpoints were the number of international normalized ratios (INRs) per 30 days, percentage of INRs within, above, and below target range, and warfarin-related adverse events. Results: A total of 79 patients were included-37 with and 42 without MHCs. Patients were mostly male (n = 47; 59.5%) and prescribed warfarin for atrial fibrillation (n = 45; 57.0%). There were no differences in overall TTR between those with (59.6%; interquartile range = 41.8-73.4) versus without (63.4%; interquartile range = 46.7-73.6) MHCs (P = .542). Secondary outcomes showed no differences in the frequency or percentage of INRs in, above, or below target range (all P > .05). However, there were about twice as many hemorrhagic complications in the group with MHCs (27% vs 11.9%; P = .149). Conclusion: Patients with MHCs experienced no difference in overall TTR as compared to patients without MHCs. However, there was a non-statistically significant reduction in TTR, which would be consistent with limited existing data and demonstrates possible reproducibility to a rural, underserved patient population. Future research is needed to validate these outcomes.

Safety and Efficacy of Apixaban, Rivaroxaban, and Warfarin in End-Stage Renal Disease With Atrial Fibrillation: A Systematic Review and Meta-Analysis

BackgroundThe use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited. MethodsElectronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model. ResultsA total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33–0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64–1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50–1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59–3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis. ConclusionsApixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.

The Role of Antithrombotic Therapy in Heart Failure.

Heart failure is a major contributor to global morbidity and mortality burden affecting approximately 1-2% of adults in developed countries, mounting to over 10% in individuals aged >70 years old. Heart failure is characterized by a prothrombotic state and increased rates of stroke and thromboembolism have been reported in heart failure patients compared with the general population. However, the impact of antithrombotic therapy on heart failure remains controversial. Administration of antiplatelet or anticoagulant therapy is the obvious (and well-established) choice in heart failure patients with cardiovascular comorbidity that necessitates their use, such as coronary artery disease or atrial fibrillation. In contrast, antithrombotic therapy has not demonstrated any clear benefit when administered for heart failure per se, i.e. with heart failure being the sole indication. Randomized studies have reported decreased stroke rates with warfarin use in patients with heart failure with reduced left ventricular ejection fraction, but at the expense of excessive bleeding. Non-vitamin K oral anticoagulants have shown a better safety profile in heart failure patients with atrial fibrillation compared with warfarin, however, current evidence about their role in heart failure with sinus rhythm is inconclusive and further research is needed. In the present review, we discuss the role of antithrombotic therapy in heart failure (beyond coronary artery disease), aiming to summarize evidence regarding the thrombotic risk and the role of antiplatelet and anticoagulant agents in patients with heart failure.

Abstract 268: Trends and Predictors of Novel Oral Anticoagulant versus Warfarin Use in Patients With Non-valvular Atrial Fibrillation: Opportunities for Improving Care

Objectives: While NOACs are known to have an excellent safety profile, providers have historically been cautious when prescribing this medication class to specific patient populations, including those with a low GFR, advanced age, elevated bleeding risk, and a history of CAD. This study aims to examine the role of patient demographics, comorbid conditions, and health indices on anticoagulant prescribing practices with hopes to identify patient populations for which we have not yet maximized the use of NOACs in clinical practice. Methods: We performed a retrospective analysis looking specifically at a cohort of all outpatients in a large health system from 2010 to 2019 who were newly diagnosed with NVAF. The data was then split into an early versus contemporary NOAC era defined as when the incidence of NOAC prescriptions surpassed that of Warfarin. Patient demographics, comorbid conditions, and health indices were then analyzed to elucidate which of these factors most influence anticoagulant selection. Finally, we examined how the influence of these factors had changed over time. Results: Our sample consisted of 19,989 patients; 7606 on Warfarin and 12,383 on a NOAC. The early-NOAC cohort consisted of 6041 patients; 4143 on Warfarin and 1458 on a NOAC. The contemporary-NOAC cohort consisted of 13,948 patients; 3463 on Warfarin and 10,925 on a NOAC. Table 1 illustrates the adjusted odds ratios for NOAC versus Warfarin selection. Overall, the most significant predictors of AC selection were patient age, income, insurance type, and history of coronary artery disease, diabetes, and systolic heart failure. Conclusions: We have identified changes over time in anticoagulant prescribing practices for NVAF. Factors such as advanced age and a history of major bleeding have shown a shift towards NOACs, which is consistent with the evidence in the literature supporting NOACs’ safety in these populations. On the other hand, irrespective of mounting evidence that NOACs are safe in patients with a low GFR or a history of CAD, our findings indicate that providers still favor Warfarin in these populations, suggesting that there is still an opportunity to improve our prescribing practices to provide the best high-quality, evidence-based care.

Effect of Warfarin on Ischemic Stroke, Bleeding, and Mortality in Patients with Atrial Fibrillation Receiving Peritoneal Dialysis.

There is limited information on the risks and benefits of anticoagulation in patients with atrial fibrillation receiving peritoneal dialysis. The aim was to determine the risk of mortality, ischemic stroke, and bleeding associated with warfarin use in patients with atrial fibrillation receiving peritoneal dialysis. This is a retrospective observational study of a multi-ethnic cohort of patients with atrial fibrillation receiving peritoneal dialysis in the United States. Using a dialysis registry, we identified 476 patients with atrial fibrillation receiving peritoneal dialysis. Among these patients, 115 (24%) were treated with warfarin. Cox proportional hazard models were used to compare risks of mortality, ischemic stroke and bleeding between the groups. Compared to untreated patients, patients receiving warfarin were older (67.3 ± 10.8 vs 62.9 ± 13.3years) and more likely to be white (42% vs 31%). Prevalence of comorbidities including hypertension, hyperlipidemia, diabetes, heart failure, and prior ischemic stroke were similar between the two groups. All cause mortality rates were 19.9 per 100 person-years in the warfarin group and 21.0 per 100 person-years in the untreated group. There was no difference between groups in the risk of mortality [hazard ratio (HR) 0.8, 95% confidence interval (CI) 0.53-1.2, p = 0.28], ischemic stroke (HR 2.3, 95% CI 0.94-5.4, p = 0.07), hemorrhagic stroke (HR 2.0, 95% CI 0.32-12.8, p = 0.46), gastrointestinal bleeding (HR 0.92, 95% CI 0.39-2.2, p = 0.86), or any bleeding (HR 1.2, 95% 0.60-2.3, p = 0.65). Even in the subgroup of patients with > 70% time in therapeutic range, no association was seen between warfarin treatment and mortality. There is no significant association between warfarin treatment with risks of mortality, ischemic stroke or bleeding in patients with atrial fibrillation receiving peritoneal dialysis.

Renal function and risk of stroke and bleeding in patients undergoing catheter ablation for atrial fibrillation: Comparison between uninterrupted direct oral anticoagulants and warfarin administration

The effect of uninterrupted oral anticoagulant use in patients with chronic kidney disease (CKD) during catheter ablation for atrial fibrillation (AF) is not fully understood. The present study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulant (DOAC) use compared with those of uninterrupted warfarin use in patients undergoing catheter ablation for AF stratified by various renal function groups. A total of 2091 patients were retrospectively included in this study. The study population was divided into 4 groups: creatinine clearance level ≥80 mL/min (n = 1086), 50-79 mL/min (n = 774), 15-49 mL/min (n = 209), and <15 mL/min (n = 22). We investigated periprocedural complications and compared them between uninterrupted DOAC and warfarin groups. There was no significant difference in thromboembolic events among the 4 groups (0.6%, 0.6%, 1.0%, and 0%, respectively; P = .792). However, major bleeding events (0.9%, 1.4%, 4.8%, and 4.5%; P < .001) and minor bleeding events (4.1%, 6.1%, 11.5%, and 13.6%; P < .001) primarily occurred in patients with CKD. The rate of periprocedural complications in the DOAC group was similar to that in the warfarin group for each renal function category. Adverse events did not differ after adjustment using propensity score-matched analysis. Multivariate analysis showed that lower body weight, antiplatelet drug use, initial ablation session, and CKD were independent predictors of adverse events. The periprocedural bleeding risk was increased in patients with CKD. Uninterrupted DOAC and warfarin administration during catheter ablation for AF in patients with CKD is feasible and effective.

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer

BackgroundVenous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease.MethodsThe study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias.ResultsIn total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death.ConclusionsWe found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P=0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P=0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P=0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P=0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications.

Use of Oral Anticoagulation in the Management of Atrial Fibrillation in Patients with ESRD: Pro.

Warfarin has had a thin margin of benefit over risk for the prevention of stroke and systemic embolism in patients with ESRD because of higher bleeding risks and complications of therapy. The successful use of warfarin has been dependent on the selection of patients with nonvalvular atrial fibrillation at relatively high risk of stroke and systemic embolism and lower risks of bleeding over the course of therapy. Without such selection strategies, broad use of warfarin has not proven to be beneficial to the broad population of patients with ESRD and nonvalvular atrial fibrillation. In a recent meta-analysis of use of warfarin in patients with nonvalvular atrial fibrillation and ESRD, warfarin had no effect on the risks of stroke (hazard ratio, 1.12; 95% confidence interval, 0.69 to 1.82; P=0.65) or mortality (hazard ratio, 0.96; 95% confidence interval, 0.81 to 1.13; P=0.60) but was associated with increased risk of major bleeding (hazard ratio, 1.30; 95% confidence interval, 1.08 to 1.56; P<0.01). In pivotal trials, novel oral anticoagulants were generally at least equal to warfarin for efficacy and safety in nonvalvular atrial fibrillation and mild to moderate renal impairment. Clinical data for ESRD are limited, because pivotal trials excluded such patients. Given the very high risk of stroke and systemic embolism and the early evidence of acceptable safety profiles of novel oral anticoagulants, we think that patients with ESRD should be considered for treatment with chronic anticoagulation provided that there is an acceptable bleeding profile. Apixaban is currently indicated in ESRD for this application and may be preferable to warfarin given the body of evidence for warfarin and its difficulty of use and attendant adverse events.

Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation: a nationwide cohort study.

Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse. To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE) and intracranial bleeding in AF. Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects as standardized differences in 1-year absolute risks. Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient-specific follow-up limited to the first 2 years, 1054 stroke/TE occurred and 261 intracranial bleedings. Standardized absolute risk (95% CI) of stroke/TE at 1 year after initiation of VKA was 2.01% (1.80% to 2.21%). In relation to VKA, the absolute risk differences were for dabigatran 0.11% (-0.16% to 0.42%), rivaroxaban 0.05% (-0.33% to 0.48%), and apixaban 0.45% (-0.001% to 0.93%). For the intracranial bleeding outcome, the standardized absolute risk at 1 year was for VKA 0.60% (0.49% to 0.72%); the corresponding absolute risk differences were for dabigatran -0.34% (-0.47% to - 0.21%), rivaroxaban -0.13% (-0.33% to 0.08%), and apixaban -0.20% (-0.38% to - 0.01%). Among anticoagulant-naïve AF patients, treatment with NOACs was not associated with significantly lower risk of stroke/TE compared with VKA, but intracranial bleeding risk was significantly lower with dabigatran and apixaban.

Patients' Characteristics Affect the Survival Benefit of Warfarin Treatment for Hemodialysis Patients with Atrial Fibrillation. A Historical Cohort Study

Background: Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population. Methods: A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled. Results: VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction <0.01). Moderation analysis showed that patients' age and clinical history of stroke strongly influenced warfarin-related benefits on survival. Conclusion: VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

Stroke, Major Bleeding, and Mortality Outcomes in Warfarin Users With Atrial Fibrillation and Chronic Kidney Disease: A Meta-Analysis of Observational Studies.

The use of warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) can be problematic because of increased bleeding risk. We performed a systematic review and meta-analysis of observational studies that evaluated the use of warfarin in patients with AF and CKD to evaluate the risks of ischemic stroke/thromboembolism, major bleeding, and mortality. PUBMED, EMBASE, CINAHL, ProQuest, and Google Scholar databases were electronically searched through January 12, 2015. Additionally, a manual search was performed for relevant references. Random-effects model was used to estimate the pooled hazard ratio (HR) with 95% CI. CKD was divided into non-end-stage CKD and end-stage CKD (on renal replacement therapy) and separate analyses were performed. Thirteen publications from 11 cohorts (six retrospective and five prospective) including >48,500 total patients with >11,600 warfarin users were included in the meta-analysis. In patients with AF and non-end-stage CKD, warfarin resulted in a lower risk of ischemic stroke/thromboembolism (HR, 0.70; 95% CI, 0.54-0.89; P = .004) and mortality (HR, 0.65; 95% CI, 0.59-0.72; P < .00001), but had no effect on major bleeding (HR, 1.15; 95% CI, 0.88-1.49; P = .31). In patients with AF and end-stage CKD, warfarin had no effect on the risks of stroke (HR, 1.12; 95% CI, 0.69-1.82; P = .65) and mortality (HR, 0.96; 95% CI, 0.81-1.13; P = .60), but increased the risks of major bleeding (HR, 1.30; 95% CI, 1.08-1.56; P = .005). Based on this meta-analysis, the use of warfarin for AF may have an unfavorable risk/benefit ratio in patients with end-stage CKD but not in those with non-end-stage CKD.

Use of Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation Who Have a History of Intracranial Hemorrhage.

The risk of further intracranial hemorrhage (ICH) and the benefit of stroke risk reduction with the use of oral anticoagulants for patients who have atrial fibrillation with a history of ICH remain unclear. We aimed to investigate the risks and benefits in patients who have atrial fibrillation with a previous ICH treated with warfarin or antiplatelet drugs in comparison with no antithrombotic therapies. This study used the National Health Insurance Research Database in Taiwan. Among 307 640 patients who have atrial fibrillation with a CHA2DS2-VASc score ≧2, 12 917 patients with a history of ICH were identified and were assigned to 1 of 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Among patients with previous ICH, the rate of ICH and ischemic stroke in untreated patients was 4.2 and 5.8 per 100 person-years, respectively. The annual ICH and ischemic stroke rates in warfarin users were 5.9% and 3.4%, respectively. Among users of antiplatelet agents, the rates were 5.3% per year and 5.2% per year, respectively. The number needed to treat for preventing 1 ischemic stroke was lower than the number needed to harm for producing 1 ICH with warfarin use for patients with a CHA2DS2-VASc score ≧6 (37 versus 56). The number needed to treat was higher than the number needed to harm for patients with a CHA2DS2-VASc score <6 (63 versus 53). Warfarin use may be beneficial for patients who have atrial fibrillation with a previous ICH having a CHA2DS2-VASc score ≧6. Whether the use of non-vitamin K antagonist oral anticoagulants could lower the threshold for treatment deserves further study.

Effectiveness and Safety of Warfarin in Dialysis Patients With Atrial Fibrillation: A Meta-Analysis of Observational Studies.

In routine practice, warfarin is widely used in dialysis patients with atrial fibrillation (AF) for stroke prevention though the ratio of risks to benefits remains unclear. Recent cohort studies investigating the association between warfarin use and the risks of stroke and bleeding in dialysis patients with AF present conflicting results.The objective of this study was to assess the effectiveness and safety of warfarin use in patients with AF undergoing dialysis.Three databases PubMed, EMBASE, and OVID were searched from their inception to August 2015.Observational studies which assessed the ischemic stroke or bleeding risk of warfarin use in dialysis patients with AF were included. Two reviewers independently extracted data and assessed methodological quality based on the Newcastle–Ottawa Scale score. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model and heterogeneity was assessed based on the Cochrane Q-statistic test and the I2 statistic. Metaregression analyses were performed to explore the source of heterogeneity.A total of 11 eligible studies with 25,407 patients were included in the analysis. Warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for ischemic stroke (HR 0.95, 95% CI 0.66–1.35). Sensitivity analyses found results to be robust. Metaregression analysis showed that demographic feature, clinical characteristics, or study-level variable had no impact of warfarin use on stroke risk. In addition, warfarin use was associated with a 27% higher risk for bleeding (95% CI 1.04–1.54). Overall, warfarin use did not have a significant association with reduced mortality (95% CI 0.96–1.11).It appears that warfarin use is not beneficial in reducing stroke risk, but with a high risk for bleeding in dialysis patients with AF. Randomized trials are needed to determine the risk-benefit ratio of warfarin in dialysis patients with AF.

The Impact of Uninterrupted Warfarin on Hand and Wrist Surgery

To determine the impact of uninterrupted use of warfarin on hand and wrist surgery. This single-center, prospective cohort trial enrolled adult patients undergoing hand and wrist surgery. Between May 2009 and August 2014, 47 surgical patients receiving uninterrupted warfarin (50 procedures) were enrolled and matched as a group by age and procedure type to 48 surgical patients (50 procedures) who were not prescribed warfarin. Complications, defined as bleeding, infection, or wound dehiscence requiring reoperation, were recorded for each group. Surgical outcome measures were composed of objective findings affected by surgical site bleeding (ie, ecchymosis extent, hematoma presence, 2-point discrimination) and standardized patient-rated assessments (Quick-Disabilities of the Arm, Shoulder, and Hand, and visual analog scales: pain and swelling). We collected data preoperatively and at 2 and 4 weeks postoperatively. Statistical analyses contrasted complications and outcomes data between patient groups. One procedure (2%; 95% confidence interval, 0% to 11%) in a patient taking warfarin was complicated by hematoma requiring reoperation resulting from an elevated postoperative international normalized ratio of 5.4. There were no complications among controls (0%; 95% confidence interval, 0% to 7%). At 2 weeks postoperatively, patients receiving warfarin more frequently had hematomas (28% vs 10%) and demonstrated a greater extent of ecchymosis from the surgical incision (50 vs 19 mm). At 4 weeks, no differences existed in hematoma presence or extent of ecchymosis between groups. The incidence of transiently elevated 2-point discrimination was not different between groups (10% warfarin; 6% controls). Visual analog scores for pain and swelling were not significantly different between groups at any time. Differences in Quick-Disabilities of the Arm, Shoulder, and Hand scores between groups did not exceed a minimal clinically important difference. Uninterrupted use of warfarin in patients undergoing surgery of the hand and wrist was associated with an infrequent risk of bleeding complication requiring reoperation. Increased rates of hematoma and ecchymosis in patients taking warfarin normalized by 4weeks postoperatively. Therapeutic II.