Aims: In patients undergoing catheter ablation for atrial fibrillation (AF), direct oral anticoagulants (DOACs) are as effective and safe as the vitamin K antagonist (VKA) warfarin. Phenprocoumon has a different pharmacokinetic profile compared with warfarin and is the most used VKA in Germany. The aim of the study was to compare DOAC with phenprocoumon. Methods and results: In this retrospective single-centre cohort study, 1735 patients who underwent 2219 consecutive catheter ablations for AF between January 2011 and May 2017 were included. All patients were in-hospital for at least 48 h after catheter ablation. The primary outcome was defined as peri-procedural thrombo-embolic events. The secondary outcome was any bleeding according to the International Society on Thrombosis and Haemostasis (ISTH). The mean age of the patients was 63.3 years. Phenprocoumon was prescribed in 929 (42%) of the cases, and in 697 (31%) dabigatran, 399 (18%) rivaroxaban, and 194 (9%) apixaban. During hospitalization, 37 (1.6%) thrombo-embolic events occurred, including 23 transient ischaemic attacks (TIAs). Compared with the use of phenoprocoumon, the use of DOAC was significantly associated with a lower thrombo-embolic risk [16 (1.2%) vs. 21 (2.2%), odds ratio (OR)], 0.5 [95% confidence interval (CI) 0.2-0.9], P = 0.04. No statistically significant association with bleeding risk was observed [phenprocomoun: 122 (13%); DOAC: 163 (12.6%); OR 0.9 (95% CI 0.7-1.2); P = 0.70]. Interruption of oral anticoagulation (OAC) was associated with an increased risk for thrombo-embolic complications [OR 2.2 (1.1-4.3); P = 0.031], and bleeding [OR 2.5 (95% CI 1.8-3.2), P = 0.001]. Conclusion: In patients undergoing catheter ablation for AF, the use of DOAC was associated with a reduced risk of thrombo-embolic events compared with phenprocoumon. Non-interrupted oral anticoagulation (OAC) therapy was associated with a reduced risk of peri-procedural thrombo-embolic and any bleeding complications.

Objectives: To assess the comparative budget and health impact of lower-dose dabigatran versus reduced doses of apixaban and rivaroxaban in atrial fibrillation (AF) patients eligible for a lower-/reduced-dose due to individual patient characteristics in the Netherlands. Methods: A budget impact model was developed in accordance with ISPOR guidelines. A 3-year-time horizon was considered, and analyses were conducted from a Dutch healthcare payer's perspective. The model applies published data to local AF-epidemiology, allowing calculations to estimate clinical events (strokes and haemorrhages) and costs. The analyses were based on real-world outcomes from patients with AF receiving a first direct oral anticoagulant (DOAC) prescription for low-dose dabigatran (110 mg) and a reduced dose of apixaban (2.5 mg) or rivaroxaban (15 mg). Two situations of switching treatments from one to another DOAC were modelled: switching from apixaban to dabigatran and from rivaroxaban to dabigatran. Base case results were given as savings per 100 patient-year, per total Dutch population, and events avoided. A univariate sensitivity analysis was conducted to explore the uncertainty around epidemiological and event costs input data. Scenario analyses were performed to estimate the effect of different market shares and potential price reductions due to future patent expiry for the total real-world population from the Netherlands. Results: The 3-years outcomes of switching patients eligible for a lower-/reduced-dose due to individual patient characteristics from apixaban or rivaroxaban to dabigatran resulted in cost savings estimated at €157 or €72 thousand per 100 patient-years, respectively, or €146 million per total Dutch population. Looking into the clinical events, dabigatran reflected the lowest number of mortalities, ischemic strokes, major bleeding, non-major bleeding, and haemorrhagic stroke compared to apixaban and rivaroxaban. The sensitivity analysis consistently reflected cost savings, with the ischeamic stroke events having the biggest impact. Accounting for the Dutch situation, both scenarios showed total savings ranging from €45 to €229 million over 3 years. Conclusions: Switching eligible AF-patients from reduced-dose apixaban or rivaroxaban to lower-dose dabigatran has the potential to reduce healthcare payer's budget expenditures and provide health gains. Cost savings can potentially be further enhanced by market share adjustments and further price reductions.

Introduction: Oral anticoagulants (OACs) should generally be continued lifelong in patients with atrial fibrillation (AF) to ensure optimal benefits, unless contraindications arise. However, discontinuation of OACs might occur for various reasons, potentially affecting clinical outcomes. In this review, we synthesized evidence on the clinical outcomes following OAC discontinuation in patients with AF. Methods: We conducted a systematic review and meta-analysis using PubMed, Embase and Scopus. Cohort or case-control studies were included if data were available on clinical outcomes of OAC discontinuation, compared with continuation, in patients with AF. A random-effect meta-analyses were conducted for key outcomes of stroke, mortality, and major bleeding. Results: Eighteen observational studies having a total of 283,418 patients were included. Discontinuation significantly increased the risk of stroke (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.58-2.23), all-cause (HR 1.90; 95% CI 1.40-2.59) and cardiovascular (HR 1.83; 95% CI 1.06-3.18) mortality. The risk of major bleeding was not significantly different between the discontinued and continued groups (HR 1.04; 95% CI 0.72-1.52). Conclusions: Discontinuation of OAC therapy was associated with an increased risk of stroke and mortality, with no difference in the risk of major bleeding. Acknowledging heterogeneity among the studies, the findings underline the need to ensure continuity of OAC therapy in patients with AF to prevent thrombotic complications and associated mortality.

Objective: To describe the clinical profile, risk of complications and impact of anticoagulation in COVID-19 hospitalized patients, according to the presence of atrial fibrillation (AF). Methods: Multicenter, retrospective, and observational study that consecutively included patients >55 years admitted with COVID-19 from March to October 2020. In AF patients, anticoagulation was chosen based on clinicians' judgment. Patients were followed-up for 90 days. Results: A total of 646 patients were included, of whom 75.2% had AF. Overall, mean age was 75 ± 9.1 years and 62.4% were male. Patients with AF were older and had more comorbidities. The most common anticoagulants used during hospitalization in patients with AF were edoxaban (47.9%), low molecular weight heparin (27.0%), and dabigatran (11.7%) and among patients without AF, these numbers were 0%, 93.8% and 0%. Overall, during the study period (68 ± 3 days), 15.2% of patients died, 8.2% of patients presented a major bleeding and 0.9% had a stroke/systemic embolism. During hospitalization, patients with AF had a higher risk of major bleeding (11.3% vs 0.7%; p < .01), COVID-19-related deaths (18.0% vs 4.5%; p = .02), and all-cause deaths (20.6% vs 5.6%; p = .02). Age (HR 1.5; 95% CI 1.0-2.3) and elevated transaminases (HR 3.5; 95% CI 2.0-6.1) were independently associated with all-cause mortality. AF was independently associated with major bleeding (HR 2.2; 95% CI 1.1-5.3). Conclusions: Among patients hospitalized with COVID-19, patients with AF were older, had more comorbidities and had a higher risk of major bleeding. Age and elevated transaminases during hospitalization, but not AF nor anticoagulant treatment increased the risk of all-cause death.

Objective: To analyze the clinical effects and economic costs between Warfarin and novel oral anticoagulants in elderly patients with atrial fibrillation (AF). Methods: This is a retrospective study. A total of 680 elderly AF patients receiving oral anticoagulants for the first time were selected as subjects and assigned into Group A, B and C. Patients in group A, B and C were given dabigatran etexilate, rivaroxaban and warfarin, respectively. Patients were followed up for 2 years. This study compared indicators of left ventricular diastolic function such as left ventricular posterior wall in end-diastole (LVPWd), minimum peak velocity in early diastole phase and maximum peak velocity in late diastole phase, indicators of myocardial ischemia including creatine kinase isoenzyme, lactate dehydrogenase (LDH) and myoglobin, as well as other outcomes including adverse events incidences and treatment costs, among the three groups. Results: After treatment, LVPWd was found to be obviously lower in group A and group B than that in group C, while the minimum peak velocity in early diastole phase was markedly more in group A and B than that in group C (all P<0.05). In addition, the concentrations of myoglobin and LDH were significantly reduced in group A and B than those in group C (all P<0.05). The occurrence rate of adverse events was significantly lower in group A and B than that in group C (P<0.05). Moreover, treatment cost was markedly less in group A and B than that in group C (P<0.05). Conclusion: Compared with warfarin, dabigatran etexilate and rivaroxaban not only have the ability to inhibit the myocardial ischemia indicators and improve left ventricular diastolic function while reducing the incidence of adverse events, but they also offer certain cost-effectiveness advantages for elderly patients with AF.

Purpose: Over the last decade, the use of direct oral anticoagulants (DOACs) has strongly increased. We aimed to describe and compare risk profiles including potential changes over time among persons with non-valvular atrial fibrillation initiating treatment with different DOACs or phenprocoumon (vitamin K antagonist) between 2011 and 2019 in Germany. Patients and methods: Using the German Pharmacoepidemiological Research Database (GePaRD; claims data of ~20% of the German population), we identified persons with a first dispensing of phenprocoumon or a DOAC and a diagnosis of non-valvular atrial fibrillation between August 2011 and December 2019. We described the morbidity of included patients prior to treatment initiation, stratified by year of treatment initiation. Results: Overall, we included 448,028 new users (phenprocoumon: N = 118,117, rivaroxaban: N = 130,997, apixaban: N = 130,300, edoxaban: N = 38,128, dabigatran: N = 30,486). Comparing new DOAC users in 2019, the proportion with prior ischemic stroke was highest for dabigatran (17%) and lowest for rivaroxaban (8%). The proportion with prior major bleeding was also highest for dabigatran (25%) and lowest for edoxaban (20%). New users of apixaban were oldest and, eg, showed the highest prevalence of congestive heart failure. Changes over time were most pronounced for phenprocoumon. For example, among persons initiating phenprocoumon in 2012 vs 2019, the proportion with prior major bleeding increased from 18% to 35%; the proportion with renal disease increased from 20% to 36% and the proportion with liver disease from 18% to 24%. Conclusion: This study demonstrated differences in risk profiles between new users of different oral anticoagulants and substantial changes over time among new phenprocoumon users. These differences have to be considered in head-to-head comparisons of these drugs based on observational data, especially regarding potential unmeasured confounding.

Background: Stroke prevention with oral anticoagulant (OAC) therapy, including non-vitamin K antagonist oral anticoagulants (NOACs), is recommended in patients with atrial fibrillation (AF). This analysis describes the antithrombotic prescription patterns for Chinese patients enrolled post-dabigatran approval during Phase II and III of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) program in China. Methods: Patients aged ≥ 18 years with newly diagnosed (< 3 months before baseline visit) nonvalvular AF at risk of stroke (CHA2DS2-VASc score ≥ 1) were consecutively enrolled in the GLORIA-AF registry. This cross-sectional analysis provides descriptive comparison of Chinese patients in Phase III (2015-2016) with those enrolled in Phase II (2013-2014). Results: Overall, 1,018 and 1,911 Chinese patients were eligible for analysis in Phase II and III, respectively. Most patients (69.6% and 69.1%, respectively) had high stroke risk (CHA2DS2-VASc score ≥ 2 for males and ≥ 3 for females). High bleeding risk (HAS-BLED score ≥ 3) rates were similar (17.3% for Phase II, 17.6% for Phase III). In Phase II, 5.8%, 15.2%, 36.7% and 42.2% of patients were prescribed NOACs, vitamin K antagonists (VKAs), antiplatelet therapies or no antithrombotic treatment, respectively. The corresponding figures were 17.2%, 23.5%, 37.4% and 21.8% for patients in Phase III, with an overall increase in OAC prescriptions (NOACs or VKAs). In patients with high stroke risk, the prescription patterns in Phase II were 5.6%, 14.4%, 41.0% and 38.9% for NOACs, VKAs, antiplatelets or no antithrombotic treatment, respectively. The respective proportions in Phase III were 15.1%, 23.5%, 40.9% and 20.5%. Conclusions: Since the availability of dabigatran in China, the overall trend of OAC, including NOAC, prescriptions in Chinese patients with nonvalvular AF has increased over time, albeit with VKAs as the most common antithrombotic treatment. Most patients, including those at high stroke risk, remain undertreated according to best practice guidelines.

No abstract available.

Background: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. Method: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. Results: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. Conclusion: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Whether there are differences in direct oral anticoagulants efficacy and safety in patients with atrial fibrillation (AF) combined with hypertension is unclear. We therefore conducted a multicenter retrospective cohort study to assess the differences in the efficacy and safety of direct oral anticoagulants in patients with AF combined with hypertension. This multicenter retrospective cohort study was based on data from 15 centers in China and included 2086 patients with AF. We divided the patients into dabigatran and rivaroxaban groups according to their direct oral anticoagulants. Propensity score matching was used to balance the covariates between the groups. Due to our limited sample size, the number of cases of some clinical events with low incidence was small. During a mean follow-up period of 10 months, a total of 268 (12.9%) bleeding events occurred, including 27 (1.3%) major bleeding events and 241 (11.6%) minor bleeding events, and 45 (2.2%) thromboembolic events. In patients with AF combined with hypertension, rivaroxaban was associated with a higher major bleeding incidence than dabigatran (odds ratio [OR], 2.89 [95% confidence interval [CI, 1.22-6.87]; P = .012). In contrast, the risk of thromboembolism and minor bleeding was similar for rivaroxaban (OR, 0.55 [95%CI, 0.29-1.01]; P = .069) and dabigatran (OR, 0.82 [95%CI, 0.63-1.08]; P = .150). Based on the results of this study, in patients with AF and hypertension treated with direct oral anticoagulants, the incidence of thromboembolism and minor bleeding was not statistically different between dabigatran and rivaroxaban, but compared with rivaroxaban, dabigatran was associated with a lower risk of major bleeding.

Background: The optimal timing of initiating or resuming anticoagulation after acute ischemic stroke (AIS) or transient ischemic attack (TIA) in patients with atrial fibrillation (AF) is debated. Dabigatran, a non-vitamin K oral anticoagulant (NOAC), has shown superiority against vitamin K antagonists (VKA) regarding hemorrhagic complications. Aims: In this registry study, we investigated the initiation of dabigatran in the early phase after AIS or TIA. Methods: PRODAST (Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA) is a prospective, multicenter, observational, post-authorization safety study. We recruited 10,039 patients at 86 German stroke units between July 2015 and November 2020. A total of 3,312 patients were treated with dabigatran or VKA and were eligible for the analysis that investigates risks for major hemorrhagic events within 3 months after early ( 7 days) or late (> 7 days) initiation of dabigatran or VKA initiated at any time. Further endpoints were recurrent stroke, ischemic stroke, TIA, systemic embolism, myocardial infarction, death, and a composite endpoint of stroke, systemic embolism, life-threatening bleeding and death. Results: Major bleeding event rates per 10,000 treatment days ranged from 1.9 for late administered dabigatran to 4.9 for VKA. Early or late initiation of dabigatran was associated with a lower hazard for major hemorrhages as compared to VKA use. The difference was pronounced for intracranial hemorrhages with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval (CI): 0.10–2.21) for early dabigatran use versus VKA use and an adjusted HR of 0.09 (95% CI: 0.00–13.11) for late dabigatran use versus VKA use. No differences were found between early initiation of dabigatran versus VKA use regarding ischemic endpoints. Conclusions: The early application of dabigatran appears to be safer than VKA administered at any time point with regards to the risk of hemorrhagic complications and in particular for intracranial hemorrhage. This result, however, must be interpreted with caution in view of the low precision of the estimate.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent conditions with a significant healthcare burden, and represent the main indications for anticoagulation. Direct oral anticoagulants (DOACs) are the first choice treatment of AF/VTE, and have become the most prescribed class of anticoagulants globally, overtaking vitamin K antagonists (VKAs). Compared to VKAs, DOACs have a similar or better efficacy/safety profile, with reduced risk of intracerebral hemorrhage (ICH), while the risk of major bleeding and other bleeding harms may vary depending on the type of DOAC. We have critically reviewed available evidence from randomized controlled trials and observational studies regarding the risk of bleeding complications of DOACs compared to VKAs in patients with AF and VTE. Special patient populations (e.g., elderly, extreme body weights, chronic kidney disease) have specifically been addressed. Management of bleeding complications and possible resumption of anticoagulation, in particular after ICH and gastrointestinal bleeding, are also discussed. Finally, some suggestions are provided to choose the optimal DOAC to minimize adverse events according to individual patient characteristics and bleeding risk.

Introduction: Deciding whether to stop or extend anticoagulant therapy indefinitely after completing at least 3 months of initial treatment for a first unprovoked venous thromboembolism (VTE) remains a challenge for clinicians, patients and policy makers. Guidelines suggest an indefinite duration of anticoagulant therapy in these patients, yet its benefits, harms and costs have not been formally assessed. The aim of this proposed modelling study is to assess the differences in clinical benefits, harms and costs of stopping versus continuing anticoagulant therapy indefinitely for a first unprovoked VTE. Methods and analysis: We will develop a probabilistic Markov model, adopting a 1-month cycle length and a lifetime horizon, to estimate life-years, quality-adjusted life-years, costs and the incremental cost-effectiveness ratios for a simulated population of patients with a first unprovoked VTE who will receive indefinite duration of anticoagulant therapy versus a population who will not receive extended treatment after completing 3 months of initial anticoagulant therapy. The economic evaluation will adopt a third-party payer perspective relating to a Canadian publicly funded healthcare system. Estimates for the probability of relevant clinical events will be informed by systematic reviews and meta-analyses, while costs and utility values will be obtained from published Canadian sources. Stratified analyses based on sex, age and site of initial VTE will also be performed to identify subgroups of patients with a first unprovoked VTE in whom continuing anticoagulant therapy indefinitely might prove to be clinically beneficial and cost-effective over stopping treatment. We will also conduct sensitivity and scenario analyses to assess robustness of study findings to changes in individual or groups of key parameters. Ethics and dissemination: Ethical approval is not applicable for this study. The results will be disseminated through presentations at relevant conferences and in a manuscript that will be submitted to a peer-reviewed journal.

No abstract available