Gaps in guideline-recommended anticoagulation in patients with atrial fibrillation and elevated thromboembolic risk within an integrated healthcare delivery system.

BACKGROUND: Atrial Fibrillation (AF) is the leading cause of stroke, which can be reduced by 70% with appropriate oral anticoagulation (OAC) therapy. Nationally, appropriate anticoagulation rates for patients with AF with elevated thromboembolic risk are as low as 50% even across the highest stroke risk cohorts. This study aims to evaluate the variability of appropriate anticoagulation rates among patients by sex, ethnicity, and socioeconomic status within the Kaiser Permanente Mid-Atlantic States (KPMAS). METHODS: This retrospective study investigated 9513 patients in KPMAS's AF registry with CHADS2 score ≥ 2 over a 6-month period in 2021. RESULTS: Appropriately anticoagulated patients had higher rates of diabetes, prior stroke, and congestive heart failure than patients who were not appropriately anticoagulated. There were no significant differences in anticoagulation rates between males and females (71.8% vs. 71.6%%, [OR] 1.01; 95% CI, 0.93-1.11; P = .76) nor by SES-SVI quartiles. There was a statistically significant difference between Black and White patients (70.8% vs. 73.1%, P = .03) and Asian and White patients (68.3% vs. 71.6%, P = .005). After adjusting for CHADS2, this difference persisted for Black and White participants with CHADS2 scores of ≤3 (62.6% vs. 70.6%, P < .001) and for Asian and White participants with CHADS2 scores > 5 (68.0% vs. 79.3%, P < .001). CONCLUSIONS: Black and Asian patients may have differing rates of appropriate anticoagulation when compared with White patients. Characterizing such disparities is the first step towards addressing treatment gaps in AF.

Mobile health-technology integrated care in secondary prevention atrial fibrillation patients: a post-hoc analysis from the mAFA-II randomized clinical trial.

AF patients with history of thromboembolic events are at higher risk of thromboembolic recurrences, despite appropriate antithrombotic treatment. We aimed to evaluate the effect of mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway approach (mAFA intervention) in secondary prevention AF patients. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomized trial enrolled adult AF patients across 40 centers in China. The main outcome was the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization. Using Inverse Probability of Treatment Weighting (IPTW), we evaluated the effect of the mAFA intervention in patients with and without prior history of thromboembolic events (i.e., ischemic stroke or thromboembolism). Among the 3324 patients enrolled in the trial, 496 (14.9%, mean age: 75.1 ± 11.4 years, 35.9% females) had a previous episode of thromboembolic event. No significant interaction was observed for the effect of mAFA intervention in patients with vs. without history of thromboembolic events [Hazard ratio, (HR): 0.38, 95% confidence interval (CI):0.18-0.80 vs. HR 0.55, 95% CI 0.17-1.76, p for interaction = 0.587); however, a trend towards lower efficacy of mAFA intervention among AF patients in secondary prevention was observed for secondary outcomes, with significant interaction for bleeding events (p = 0.034) and the composite of cardiovascular events (p = 0.015). A mHealth-technology-implemented ABC pathway provided generally consistent reduction of the risk of primary outcome in both primary and secondary prevention AF patients. Secondary prevention patients may require further specific approaches to improve clinical outcomes such as bleeding and cardiovascular events.Trial registration: WHO International Clinical Trials Registry Platform (ICTRP) Registration number ChiCTR-OOC-17014138.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin.

BACKGROUND: Diabetes increases a patient's risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. METHODS: This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. RESULTS: We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88-0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86-0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66-1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89-0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55-0.72). CONCLUSIONS: In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

Impact of body mass index on real-world outcomes of rivaroxaban treatment in Japanese patients with non-valvular atrial fibrillation.

This sub-analysis of the XAPASS, a prospective, single-arm, observational study, aimed to evaluate relationships between body mass index (BMI) and safety (major bleeding and all-cause mortality) and effectiveness [stroke/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI)] outcomes in Japanese patients with non-valvular atrial fibrillation (NVAF) receiving rivaroxaban. Patients were categorized according to BMI (kg/m2) as underweight (< 18.5), normal weight (18.5 to < 25), overweight (25 to < 30), or obese (≥ 30). In total, 9578 patients with NVAF completed the 1-year follow-up and were evaluated; of these, 7618 patients had baseline BMI data. Overall, 542 (5.7%), 4410 (46.0%), 2167 (22.6%), and 499 (5.2%) patients were underweight, normal weight, overweight, and obese, respectively. Multivariable Cox regression analysis demonstrated that none of the BMI categories were independent predictors of major bleeding whereas being underweight was independently associated with increased all-cause mortality [hazard ratio (HR) 3.56, 95% confidence interval (CI) 2.40-5.26, p < 0.001]. The incidence of stroke/non-CNS SE/MI was higher in patients who were underweight than in those of normal weight (HR 2.11, 95% CI 1.20-3.70, p = 0.009). However, in multivariable analyses, being underweight was not identified as an independent predictor of stroke/non-CNS SE/MI (HR 1.64, 95% CI 0.90-2.99, p = 0.104). In conclusion, the high incidence of thromboembolic events and all-cause mortality in patients who were underweight highlights that thorough evaluation of disease status and comorbidities may be required in this population.

Successful COMPASS, Disappointing COMMANDER HF, What Have We Learned From These Two Trials?

Despite considerable progress in the field of heart failure about drugs and device therapy, the mortality rate of patients with heart failure remains high. Studies have shown that thromboembolism and stroke are associated with high mortality in patients with heart failure. Although warfarin therapy reduces the rate of ischemic stroke in patients with heart failure, the overall benefit from warfarin in this population seems to be offset by the increased bleeding risk. Thus, whether patients with chronic heart failure might benefit from anticoagulation, especially in patients with sinus rhythm, is still controversial. Rivaroxaban, a new oral anticoagulant, is a selective direct factor Xa inhibitor that is used to reduce thrombin generation, which may bring hope to anticoagulation in patients with heart failure. However, the COMPASS trial and recently published COMMANDER HF trial presented different results. By carefully analyzing 2 clinical trials, we think several factors might explain this different outcome.

Prophylactic anticoagulation in nephrotic syndrome prevents thromboembolic complications.

BACKGROUND: An increased incidence of thromboembolic events (TE) are reported in nephrotic syndrome (NS) leading to recommendations for prophylactic anticoagulation (PAC). However, as no randomized clinical trial has established the efficacy or risks associated with PAC, guidelines are empiric or substantiated only by estimates of risks and benefits. This study evaluates the risk of TE and hemorrhagic complications in patients with NS treated with PAC and compares to patients not receiving PAC. METHODS: We included patients diagnosed with NS from two Danish nephrology departments with different practices for the use of PAC. Patients were included if presenting with NS from September 2006 to January 2012, a P-albumin < 30 g/L, and renal biopsy confirming non-diabetic, glomerular disease. Patients aged < 16 years, on renal replacement therapy, or administered anticoagulants at the onset of NS were excluded. Bleeding episodes and/or TE were identified from patient records. Bleeding episodes were divided into minor and major bleeding. RESULTS: Of the 79 patients included, 44 patients received PAC either as low or high dose low-molecular-weight heparin (LMWH) or as warfarin with or without LMWH as bridging, while 35 did not receive PAC. P-albumin was significant lower in the PAC group compared to those not receiving PAC. Significantly more TEs was observed in the non-PAC group compared to the PAC group (4 versus 0 episodes, P = 0.035). The TEs observed included one patient with pulmonary embolism (PE), one with PE and deep vein thrombosis, one with PE and renal vein thrombosis, and one with a stroke. Five patients with bleeding episodes were identified among those receiving PAC, of which two were major and three were minor, while two patients in the non-PAC group experienced a minor bleeding episode (P = 0.45 between groups). The major bleeding episodes only occurred in patients receiving PAC in combination with low dose aspirin. CONCLUSIONS: In patients with NS the use of PAC was associated with a decreased risk of clinically significant TE, but may also be associated with more bleeding episodes although not statistically significant. Only patients treated with PAC in combination with anti-platelet therapy had major bleeding episodes.

Análise do grau de recanalização da trombose venosa profunda: estudo comparativo de pacientes tratados com varfarina versus rivaroxabana / Analysis of recanalization of deep venous thrombosis: a comparative study of patients treated with warfarin vs. rivaroxaban

Contexto A trombose venosa profunda (TVP) afeta anualmente cerca de dez milhões de pessoas no mundo e tem como principais complicações a embolia pulmonar e a síndrome pós-trombótica. O tratamento padrão é a anticoagulação, que pode ser realizada com heparinas, antagonistas da vitamina K, fondaparinux ou, mais recentemente, com anticoagulantes orais diretos (direct oral anticoagulants, DOACs). Os anticoagulantes diminuem a progressão do trombo e facilitam os mecanismos trombolíticos naturais, fato conhecido como recanalização, que pode ocorrer em graus e tempos variados, influenciados por diversos fatores, dentre eles o tipo de anticoagulação utilizado. Objetivos Avaliar o grau e o tempo de recanalização através da análise de laudos de eco-Doppler colorido (EDC) de pacientes com TVP tratados com DOACs ou com heparina + varfarina. Métodos Foram avaliados retrospectivamente os dados demográficos e os laudos dos EDC dos pacientes com TVP, tratados entre janeiro de 2009 a dezembro de 2016. Os pacientes foram divididos em dois grupos, de acordo com a terapêutica utilizada: Grupo I (heparina + varfarina): 26 pacientes; Grupo II (rivaroxabana): 51 pacientes. Os principais itens observados foram o grau e o tempo para a recanalização. Resultados Foram observadas taxas de recanalização aos 30, 90 e 180 dias de 10%, 52,5% e 78,9%, respectivamente, no Grupo I, e de 55,3%, 83,5% e 92,4%, respectivamente, no Grupo II, com diferença estatisticamente significativa (p = 0,041). Conclusões Ambos os tratamentos promoveram recanalização. Houve recanalização mais precoce no grupo de pacientes que utilizaram a rivaroxabana

Deep venous thrombosis (DVT) strikes around ten million people worldwide every year and is associated with major complications including pulmonary embolism and post-thrombotic syndrome. Anticoagulation is the standard treatment, with administration of heparins, vitamin K antagonists, fondaparinux, or, more recently, direct oral anticoagulants (DOACs). Anticoagulants reduce thrombus progression and facilitate natural thrombolytic mechanisms, leading to a phenomenon known as recanalization, which can occur in varying degrees and over variable periods of time, under influence from many different factors, including the type of anticoagulation employed. Objectives To evaluate the degree of recanalization and the time taken, by analysis of color Doppler ultrasonography (CDU) reports from patients with DVT treated with DOACs or with heparin + warfarin. Methods A retrospective analysis was conducted of demographic data and CDU reports from patients with DVT who had been treated from January 2009 to December 2016. These patients were classified into two groups, according to the treatment given: Group I (heparin + warfarin): 26 patients; or Group II (rivaroxaban): 51 patients. The primary outcomes assessed were degree of recanalization and time taken. Results Recanalization rates at 30, 90, and 180 days were 10%, 52.5%, and 78.9%, respectively, in Group I, and 55.3%, 83.5%, and 92.4%, respectively, in Group II, with statistically significant difference (p = 0.041). Conclusions Both treatments led to recanalization. Recanalization occurred earlier among patients treated with rivaroxaban

Effectiveness and Safety of Standard- and Low-Dose Rivaroxaban in Asians With Atrial Fibrillation.

BACKGROUND: Low-dose rivaroxaban (10 mg/day) has been widely used in Asia for patients with atrial fibrillation (AF), although there is a lack of evidence regarding its effectiveness. In Asians, it is unclear whether low-dose rivaroxaban is equally effective as that of the standard dose or is associated with less bleeding risk. OBJECTIVES: The aim of this study was to evaluate the effectiveness and safety of standard-dose (15 or 20 mg/day) and low-dose (10 mg/day) rivaroxaban in Asians with AF. METHODS: Using data files from the National Health Insurance Research Database between May 1, 2014, and September 30, 2015, a retrospective population-based cohort study was conducted in patients diagnosed with AF or atrial flutter and treated with low- or standard-dose rivaroxaban. Patients were followed up until the first occurrence of the study outcome or the end of the observation period (December 31, 2015). RESULTS: Among 6,558 eligible patients, a total of 2,373 and 4,185 patients took low- and standard-dose rivaroxaban, respectively. Compared to standard-dose rivaroxaban, low-dose rivaroxaban was associated with a significantly higher risk of myocardial infarction (subdistribution hazard ratio: 2.26; 95% confidence interval: 1.13 to 4.52), with similar risk of ischemic stroke, systemic embolism, major bleeding, and nonmajor clinically relevant bleeding. CONCLUSIONS: Compared to standard-dose rivaroxaban, low-dose rivaroxaban in Asian patients with AF was associated with similar risks of thromboembolism and bleeding except myocardial infarction.

The Rivaroxaban Program and the Management of Unmet Needs in Thromboembolic Disease.

Rivaroxaban is a non-vitamin K antagonist oral anticoagulant that acts as a direct factor Xa inhibitor, and is widely used for the prevention and treatment of thromboembolic disorders. As further knowledge gaps are identified in thrombosis management, the rivaroxaban research program has expanded in an attempt to elucidate the wider benefits of rivaroxaban. An increased understanding of the interactions taking place within the coagulation cascade may support a broader role for rivaroxaban (2.5 mg twice daily [bid] or 5 mg bid) in the setting of vascular protection, either alone or in combination with an antiplatelet agent. The aim of this article is to describe the potential role of rivaroxaban in the context of vascular protection and provide an overview of recently completed and ongoing randomized controlled trials of rivaroxaban in the areas of stroke prevention, venous protection and vascular protection.

Rivaroxaban vs. warfarin on extended deep venous thromboembolism treatment: A cost analysis.

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

Association of left atrial low-voltage area and thromboembolic risk in patients with atrial fibrillation.

Aims: Atrial fibrillation (AF) is associated with thromboembolic events. Currently, the CHA2DS2-VASc score is recommended for thromboembolic risk stratification in non-valvular AF patients. However, recent data suggested a potential role of atrial remodelling on thromboembolism. This study aimed to assess the association between left atrial low-voltage area (LVA) and history of clinical manifest as well as subclinical silent cerebral ischaemia (SCI) in AF patients. Methods and results: Two-hundred patients [64 ± 10.5 years, 75 women (37.5%)] with symptomatic paroxysmal (n = 88, 44%) or persistent AF undergoing pulmonary vein isolation (PVI) were prospectively enrolled. Left atrial LVA (bipolar voltage < 0.5mV) was evaluated by intra-procedural mapping (>300 points per patient) during sinus rhythm. Cerebral delayed-enhancement magnetic resonance imaging was performed after PVI for detection of pre-existing procedural-independent SCI. Over all, 17 patients (8.5%) had previous history of stroke. Pre-existing SCIs were detected in 135 patients (67.5%). Patients with previous stroke (4.0 ± 1.5 vs. 2.1 ± 1.3, P < 0.0001) and pre-existing SCI (2.7 ± 1.3 vs. 1.5 ± 1.4, P < 0.0001) had a significantly higher CHA2DS2-VASc score. LVA was significantly larger in patients with previous stroke (12.5 ± 8.5% vs. 3.4 ± 5.4%, P < 0.0001) as well as pre-existing SCI (5.8 ± 6.9% vs. 0.8 ± 1.7%, P < 0.0001). Multivariate regression analysis revealed that LVA was independently associated with the presence of SCI [hazard ratio (HR) per 1% LVA 1.13 (1.06-1.22), P = 0.0003] and history of stroke [HR per 1% LVA 1.36 (1.19-1.60), P < 0.0001] after adjustment of CHA2DS2-VASc score. Conclusion: Left atrial LVA is associated with history of stroke and SCI in patients with non-valvular AF and might improve thromboembolic risk stratification after confirmation of its predictive value in future studies.

Terapia anticoagulante na ablação e cardioversão elétrica da fibrilação atrial / Anticoagulant therapy in ablation and electric cardioversion of atrial ibrillation

tratamento da FA, os pacientes podem ser submetidos a atendimentos eletivos ou de emergência para a reversão do ritmo, incluindo a cardioversão química ou elétrica, bem como o tratamento intervencionista de ablação por cateter, visando a melhora dos sintomas e da qualidade de vida. Em todas as modalidades do tratamento, a terapia anticoagulante oral (ACO) é um dos pilares do tratamento da FA, indispensável para a prevenção de eventos tromboembólicos. A incorporação dos chamados "anticoagulantes de ação direta" (DOAC) no arsenal do tratamento representou um novo paradigma, com estudos randomizados controlados e as evidências de mundo real demonstrando resultados de eficácia e segurança comparáveis com relação à varfarina, com a vantagem de menor interação medicamentosa e alimentar e menor risco de hemorragias catastróficas. O uso de DOAC para o manejo de pacientes que serão submetidos ao procedimento de ablação por cateter para o tratamento intervencionista da FA ou cardioversão elétrica/química é hoje uma realidade cada vez mais presente e tem respaldo dos estudos randomizados controlados e das experiências em vários centros hospitalares mundiais, com esquema e programação mais simples e melhor comodidade no manejo da anticoagulação

Atrial fibrillation (AF) is the most frequent sustained arrhythmia in clinical practice. During the course of AF, patients may be submitted to elective or emergency approaches for rhythm reversal, including pharmacological or electrical cardioversion, as well interventional treatment with catheter ablation, to improve the symptoms and quality of life. In all treatment modalities, it is important to emphasize that oral anticoagulant therapy (OAC) is one of the pillars of AF treatment, and is indispensable for preventing thromboembolic events. The incorporation of so-called "direct oral anticoagulants" (DOACs) into the arsenal of treatment represented a new paradigm, with randomized controlled trials and real-world clinical evidence demonstrating comparable efficacy and safety to warfarin, with the advantage of less drug and food interaction and less risk of catastrophic bleeding. The use of DOACs for the management of patients undergoing catheter ablation for interventional AF treatment or electrical/pharmacological cardioversion is increasingly used and supported by randomized controlled trials and experiences in several worldwide hospital centers, with a simpler regimen and programming and easier management of anticoagulation

The Impact of Novel Anticoagulants: Should All AF Patients Now Be Anticoagulated?

Atrial Fibrillation (AF) is accompanied by an increased risk for thromboembolic events in most affected patients. Current guidelines therefore recommend antithrombotic therapy with vitamin K antagonist (VKA) or non VKA oral anticoagulant (NOAC) in the majority of AF patients. Current AF treatment guidelines recommend that only patients younger than 65 years of age with lone AF, meaning without further concomitant risk factors for thromboembolic events should not be anticoagulated. NOACs, like the direct thrombin inhibitor dabigatran and the factor X inhibitors rivaroxaban, apixaban, and edoxaban have undergone large phase III clinical trials concerning treatment efficacy and bleeding risk in comparison to the VKA warfarin. In most cases, treatment with NOACs has been shown to decrease thromboembolic risk and/or decrease bleeding risk when compared with warfarin. Especially, as major hemorrhages like life threatening or intracranial bleeds are reduced, the question arises, if due to favourable adverse event ratios the indication for oral anticoagulation therapy should be broadened and all patients with diagnosed AF should be anticoagulated. This article gives a review on currently used thromboembolic and bleeding risk scores. Furthermore, the impact of NOAC therapy on stroke and bleeding risk is summarized, especially taking pharmacological interactions of NOAC therapy altering thromboembolic or bleeding risk into consideration. Differences of currently available guidelines are discussed. Finally, ongoing recent studies on treatment of low risk patients are debated.

Incident cancer in a cohort of 3,247 cancer diagnosis free ischemic stroke patients.

BACKGROUND: Subclinical cancer can manifest as a thromboembolic event and may be detected at a later interval in ischemic stroke survivors. We determined the rate of incident cancer and effect on cardiovascular endpoints in a large cohort of ischemic stroke survivors. METHODS: An analysis of 3,680 adults with nondisabling cerebral infarction who were followed for two years within the randomized, double-blinded VISP trial was performed. The primary intervention was best medical/surgical management plus a daily supplementation of vitamin B6, vitamin B12, and folic acid. We calculated age-adjusted rates of incidence of cancer among ischemic stroke survivors and standardized incidence ratios (SIR) with 95% confidence intervals (CI) based on comparison with age-adjusted rates in the general population. The significant variables from univariate analysis were entered in a Cox Proportional Hazards analysis to identify the association between various baseline factors and incident cancer after adjusting age, gender, and race/ethnicity. A logistic regression analysis evaluated the association between incident cancer and various endpoints including stroke, coronary heart disease, myocardial infarction, and death after adjusting age, gender, and race/ethnicity. RESULTS: A total of 3,247 patients (mean age ± SD of 66 ± 11; 2,013 were men) were cancer free at the time of enrollment. The incidence of new cancer was 0.15, 0.80, 1.2, and 2.0 per 100 patients at 1 month, 6 months, 1 year, and 2 years, respectively. The age-adjusted annual rate of cancer in patients with ischemic stroke was higher than in persons in the general population at 1 year (581.8/100,000 persons vs. 486.5/100,000 persons, SIR 1.2, 95% CI 1.16-1.24) and 2 years (1,301.7/100,000 vs. 911.5/100,000, SIR 1.4, 95% CI 1.2-1.6) after recruitment. There was a higher risk for death (odds ratio (OR) 3.1, 95% CI 1.8-5.4), and composite endpoint of stroke, coronary heart disease, and/or death (OR 1.4, 95% CI 1.0-2.2) among participants who developed incident cancer compared with those who were cancer free after adjusting for potential confounders. CONCLUSIONS: The annual rate of age-adjusted cancer incidence was higher among ischemic stroke patients compared with those in the general population. The odds of mortality were three folds higher among stroke survivors who developed incident cancer.

Treatment with novel oral anticoagulants in a real-world cohort of patients undergoing cardiac rhythm device implantations.

AIMS: The safety and efficacy of novel oral anticoagulants in patients with atrial fibrillation undergoing pacemaker or implantable cardioverter-defibrillator interventions have not been clearly defined. Therefore, we compared the incidence of bleeding and thrombo-embolic complications following cardiac rhythm device (CRD) implantations under dabigatran vs. rivaroxaban in a real-world cohort. METHODS AND RESULTS: We analysed 176 consecutive procedures performed in 93 patients treated peri-interventionally with dabigatran and 83 patients with rivaroxaban, respectively. Post-operative bleeding complications and thrombo-embolic events occurring within 30 days were compared. There were no significant differences in baseline characteristics between patients in the dabigatran and the rivaroxaban group. Most of the patients in both the groups received dual chamber or cardiac resynchronization devices (71 vs. 78%) as opposed to single-chamber systems (29 vs. 22%). In the dabigatran group, two (2%) bleeding complications (two pocket haematomas) were observed in comparison with four (5%, three pocket haematomas and one pericardial effusion) in the rivaroxaban group (P = 0.330). Three complications in the rivaroxaban group necessitated surgical intervention as opposed to none in the dabigatran group (P = 0.064). One case of a transient ischaemic attack occurred in the dabigatran group (P = 0.343). CONCLUSION: Bleeding and thrombo-embolic complications in patients treated with dabigatran or rivaroxban are rare. Further and larger studies are warranted to define the optimal anticoagulation management in patients with a need for oral anticoagulation and CRD interventions.

Spontaneous neonatal arterial thromboembolism: infants at risk, diagnosis, treatment, and outcomes.

Neonatal spontaneous arterial thromboembolism is a rare phenomenon with a high risk of morbidity and mortality. Currently, there is little information regarding common risk factors, diagnostic strategies, therapeutic interventions, and outcomes of this condition. The objective was to nucleate the best evidence regarding the disorder in order to facilitate early detection and treatment recommendations and document adverse outcomes. Web of Science, PubMed, Medline, CINAHL, Cochrane Databases, DARE, and OVID databases were searched using the following keywords: 'arterial' AND 'thrombus' OR 'thrombosis' OR 'thromboembolism' OR 'embolism' AND 'spontaneous' AND 'at birth' OR 'newborn' OR 'neonatal' OR 'fetal' AND 'umbilical cord' OR 'umbilical wall necrosis' AND 'coagulation abnormality' OR 'placenta bits' OR 'ischemic limbs'. The search yielded 172 articles, all of which were case series or single case descriptions. Twenty-seven met inclusion criteria, with a total of 53 newborns and 30 newborn pathology reports. Ultrasound was the preferred method of diagnosis and thromboembolic locations varied with the most common site being umbilical, resulting in embolism and vascular compromise. Treatment interventions and drug dosages were not standardized and ranged from use of anticoagulants to surgery and hyperbaric oxygen. The reported mortality rate was 32.8%. Recurring etiological features facilitated identification of possible sequences of events contributing to the disorder. The literature lacks empirical evidence to affirm causes and predisposing risk factors for timely diagnosis and effective treatment of spontaneous neonatal arterial thromboembolism. Further research is needed to clearly establish the causes and the efficacy of specific treatment options.

Current practices in preclinical drug development: gaps in hemostasis testing to assess risk of thromboembolic injury.

The Health and Environmental Sciences Institute Cardiac Biomarkers Working Group surveyed the pharmaceutical development community to investigate practices in assessing hemostasis, including detection of hypocoagulable and hypercoagulable states. Scientists involved in discovery, preclinical, and clinical research were queried on laboratory evaluation of endothelium, platelets, coagulation, and fibrinolysis during safety assessment studies. Results indicated that laboratory assessment of hemostasis is inconsistent among institutions and not harmonized between preclinical and clinical studies. Hemostasis testing in preclinical drug safety studies primarily focuses on the risk of bleeding, whereas the clinical complication of thrombosis is seldom assessed. Our results reveal the need for broader utilization of biomarkers to detect altered hemostasis (e.g., endothelial and platelet activation) to improve preclinical safety assessments early in the drug development process. Survey respondents indicated a critical lack of validated markers of hypercoagulability and subclinical thrombosis in animal testing. Additional obstacles included limited blood volume, lack of cross-reacting antibodies for hemostasis testing in laboratory species, restricted availability of specialized hemostasis analyzers, and few centers of expertise in animal hemostasis testing. Establishment of translatable biomarkers of prothrombotic states in multiple species and strategic implementation of testing on an industry-wide basis are needed to better avert untoward drug complications in patient populations.

Perioperative management of patients on chronic antithrombotic therapy.

Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. Procedures can be separated into those with a low bleeding risk, which generally do not require complete reversal of the antithrombotic therapy, and those associated with an intermediate or high bleeding risk. For patients who are receiving warfarin who need interruption of the anticoagulant, consideration must be given to whether simply withholding the anticoagulant is the optimal approach or whether a perioperative "bridge" with an alternative agent, typically a low-molecular-weight heparin, should be used. The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.