Oral Anticoagulants In Patients Research Articles

The rate of postoperative hematoma following risk-adapted cessation of oral anticoagulation in patients undergoing endoscopic endonasal surgery for pituitary adenomas.

This study describes the management of patients on oral anticoagulation (OAC) undergoing endoscopic endonasal transsphenoidal surgery (EETS) and analyzes the risk of postoperative hematoma and epistaxis following treatment of pituitary adenoma (PA). Patients with OAC prior to EETS for PA were analyzed in a single center retrospective case series of consecutive patients with PA, who were treated between December 2008 and July 2022. Patient data (age, sex, clinical, endocrinology, tumor histology) were entered into a SPSS® database. The rate of postoperative hemorrhage (intracranial and epistaxis) and other perioperative complications were assessed. Of 305 patients, 20 patients were on OAC prior to EETS for PA. Indications included non-valvular atrial fibrillation (AF) in 10 patients and previous venous thromboembolic event (VTE) in 8 patients, in 2 patients had overlapping indications. Twelve patients on direct oral anticoagulants (DOAC) paused medication 1-3 days (43.6 ± 23.6h) before surgery, while phenprocoumon was paused 234 ± 123.55h (min 6, max 22 days) before surgery. Baseline characteristics such as age, sex, tumor growth direction, tumor volume, and largest diameter showed no significant differences. No significant increase in postoperative hemorrhage was observed in patients with OAC compared to those without. One patient on apixaban paused 48h before surgery experienced postoperative epistaxis. Among patients without OAC, one experienced intracranial hemorrhage and seven experienced epistaxis. Patients with OAC prior to EETS for PA have no increased risk for postoperative hematoma when OAC is paused based on individual risk assessment and recent general recommendations.

Oral anticoagulation in patients with atrial fibrillation and advanced chronic kidney disease: additional kidney benefits beyond stroke prevention.

Oral anticoagulation in patients with atrial fibrillation and advanced chronic kidney disease: additional kidney benefits beyond stroke prevention.

Extended Treatment of Venous Thromboembolism with Reduced- Vs Full-Dose Direct Oral Anticoagulants in Patients at High Risk of Recurrence

BACKGROUNDVenous thromboembolism is a common, potentially fatal disease. Beyond the first 3 months of anticoagulation treatment, extending anticoagulation up to 12 or 24 months reduces the risk of recurrence by at least 80% in patients at high risk of recurrence, but this benefit is lost after stopping anticoagulation. Consequently, guidelines recommend indefinite anticoagulation in such patients. However, continued anticoagulation exposes patients to a linear increase in bleeding risk, which is expected to ultimately exceed the risk of recurrent venous thromboembolism after stopping anticoagulation.To address this issue, lower-dose anticoagulation may reduce bleeding risk while maintaining similar efficacy in preventing recurrent venous thromboembolism. In the EINSTEIN-CHOICE and AMPLIFY-EXT studies, extended reduced-dose anticoagulation appeared as effective as and safer than full-dose. However, with the inclusion of a placebo or aspirin control group, both studies enrolled patients in whom physicians were uncertain about continuing anticoagulation. Consequently, robust evidence for recommending reduced- over full-dose anticoagulation in patients with a strong indication for extended treatment is lacking. METHODSThe Reduced Dose Versus Full-Dose of Direct Oral Anticoagulant After Unprovoked Venous Thromboembolism (RENOVE) trial (ClinicalTrials.gov Identifier: NCT03285438) is an academic, multicenter, prospective, randomized, open, blinded end-point (PROBE) trial. In this study, we compared, using hierarchical sequential testing, extended anticoagulation with reduced-dose versus full-dose direct oral anticoagulants in patients with venous thromboembolism at high risk of recurrence initially treated for 6 to 24 months. Primary outcome was recurrent symptomatic venous thromboembolism (noninferiority hypothesis). Key secondary outcomes were clinically relevant bleeding and the composite of recurrent venous thromboembolism and clinically relevant bleeding (superiority hypotheses). Critical events were adjudicated by an independent committee blinded to treatment allocation. RESULTSDuring the 36-month median follow-up, recurrent venous thromboembolism occurred in 19 of 1383 patients in the reduced-dose group versus 15 of 1385 patients in the full-dose group (5-year cumulative incidence 2.2%; 95% confidence interval [CI], 1.1 to 3.3 versus 1.8%; 95% CI, 0.8 to 2.7; hazard ratio, 1.32; 95% CI, 0.67 to 2.60; P=0.23 for noninferiority). Clinically relevant bleeding occurred in 96 and 154 patients in the reduced- and full-dose groups, respectively (5-year cumulative incidence 9.9%; 95% CI, 7.7 to 12.1 versus 15.2%; 95% CI, 12.8 to 17.6). The composite outcome occurred in 113 and 166 patients in the reduced- and full dose groups, respectively (5-year cumulative incidence 11.8%; 95% CI, 9.4 to 14.3 versus 16.5%; 95% CI, 14.0 to 19.0). All-cause death occurred in 35 (4.3%) and 54 (6.1%) patients in the reduced- and full-dose groups, respectively. CONCLUSIONSIn patients with venous thromboembolism who need extended anticoagulation, the noninferiority of a reduced-dose versus a full-dose of direct anticoagulants to prevent recurrent venous thromboembolism could not be proven. In the reduced-dose group, clinically relevant bleeding and the composite of recurrent venous thromboembolism or clinically relevant bleeding were lower than in the full-dose group and did not appear to be offset by an increased risk of death or arterial thromboembolic events.

Treatment appropriateness of direct oral anticoagulants in patients with atrial fibrillation for stroke prevention: A real-world prospective study.

Inappropriate use of direct oral anticoagulants (DOACs) is common, affecting up to 30% of atrial fibrillation (AF) population receiving treatment for stroke prevention. This study assessed appropriateness of anticoagulation in anticoagulation-naive AF patients treated with DOACs during a 12-month prospective follow-up. This prospective cohort study included all anticoagulation-naive AF patients referred for anticoagulation for stroke prevention at a tertiary cardiovascular center. Participants were prospectively followed through phone call interviews by a dedicated nurse at 1, 3, 6, 9, and 12 months after enrollment. Of 403 anticoagulation-naive AF patients, rivaroxaban was prescribed for 325 patients (80.7%) and apixaban for 78 (19.3%). Inappropriate therapy was observed in 23% (76/325) and 46% (36/78) of patients treated with rivaroxaban and apixaban, respectively. Undertreatment was predominant scenario for both drugs, detected in 78.5% (78/112) of patients treated inappropriately, and was more frequently observed with apixaban versus rivaroxaban (44.8% vs 16.3%). During 12 months, inappropriate treatment was corrected in only 13% of all patients. The multivariate regression model identified creatinine clearance ≤ 49 mL/min (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.12 to 4.21), female sex (OR, 1.81; 95% CI, 1.11 to 2.97), and age ≥ 80 years (OR, 1.85; 95% CI, 1.22 to 2.83) as independent covariates associated with inappropriate dosing. Inappropriate therapy with DOACs for stroke prevention in patients with AF is common, and the dosage were corrected in few patients during the 12-month follow-up. Our findings highlight the persistent lack of knowledge regarding appropriate DOAC dosage and need for continuous education.

Safety of direct oral anticoagulants in patients with atrial fibrillation aged 80 years and older: clinical risk factors

BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding, particularly in the geriatric population. Most studies focus on predicting major bleeding, but clinically relevant non-major bleeding (CRNMB) is equally important in practice. АIM: To assess the ability of clinical factors to predict the risk of CRNMB with the use of DOACs in patients with atrial fibrillation (AF) aged 80 years and older. MATERIALS AND METHODS: A total of 367 patients on DOACs with non-valvular AF aged 80 years and older were evaluated; the median age was 84 [82; 88] years. Key characteristics of the groups were analyzed, including gender, age, and body mass index. CHA2DS2-VASc and HAS-BLED scales were used to assess the risk of ischemic stroke and bleeding, respectively. Comorbidities, Charlson Comorbidity Index, and risk factors of chronic non-communicable diseases were considered. In addition, number of medications taken, physical examination data, history of atherosclerosis, and laboratory test results were collected. RESULTS: In univariate analysis, significant risk factors for the development of CRNMB with all DOACs included higher walking frequency (p=0.022), lower heart rate (p=0.08), and history of gastric and duodenal ulcer [odds ratio 5.34; 95% confidence interval (CI) 2.31–12.0; p 0.001]. In multivariate analysis, a model for predicting CRNMB was developed using age, type of DOAC, liver disease, acute cerebrovascular accident, history of gastric and duodenal ulcer as predictors. The resulting model had a predictive accuracy of 62.6% (95% CI 57.4–67.6), a sensitivity of 66.5% (95% CI 59.4–73.1), and a specificity of 58.2% (95% CI 50.4–65.7). CONCLUSION: The study identified specific modifiable, potentially modifiable, and non-modifiable risk factors for developing CRNMB in AF patients aged 80 years and over taking DOACs. An electronic system to support medical decision making, risk factor management, and public quality of life can be created using results of the study.

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study.

This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB). Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all). DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran.

ECG-based machine learning model for AF identification in patients with first ischemic stroke.

The recurrence rate of strokes associated with atrial fibrillation (AF) can be substantially reduced through the administration of oral anticoagulants. However, previous studies have not demonstrated a clear benefit from the universal application of oral anticoagulants in patients with embolic stroke of undetermined source. Timely detection of AF remains a challenge in patients with stroke. This study aims to develop a convolutional neural network (CNN) model to accurately identify patients with AF using a 12-lead sinus-rhythm electrocardiogram (ECG) recorded around the time of the first ischemic stroke. Additionally, this study also evaluates the model's ability to predict future occurrence of AF. A CNN model was trained with ECG data from patients at Taipei Veterans General Hospital. External validation was performed on ischemic stroke patients from National Taiwan University Hospital. The model's performance was assessed for detecting AF at the stroke event and predicting future AF occurrences. The model demonstrated an area under curve (AUC) of 0.91 for internal validation and 0.69 for external validation in identifying AF at the stroke event, with sensitivity and negative predictive value both achieving 97%. Kaplan-Meier survival analysis of patients without a prior diagnosis of AF revealed a significant increase in future AF incidence among the high-risk group identified by the model (adjusted hazard ratio: 4.06; 95% confidence interval: 2.74-6.00). The CNN model effectively identifies AF in stroke patients using 12-lead ECGs and predicts future AF events, facilitating early anticoagulation therapy and potentially reducing recurrent stroke risk. Further prospective studies are warranted to confirm these findings.

Predictors and Outcomes of Inappropriate Dosing of Direct Oral Anticoagulants in Patients Receiving Transcatheter Aortic Valve Implantation.

Direct oral anticoagulant (DOAC) dose adjustment is based on age, renal function, and body weight. There is a paucity of data describing the factors associated with the prescription of inappropriate dosage and their impact on clinical outcomes among patients receiving transcatheter aortic valve implantation (TAVI). In a single-center study, 432 patients who were on long-term DOAC therapy and underwent TAVI between 2015 and 2022 were included. We analyzed the predictors and outcomes of inappropriate dosing of DOACs; namely apixaban, dabigatran, edoxaban, and rivaroxaban. A composite endpoint, including all-cause mortality, life-threatening/major bleeding, stroke, peripheral thromboembolic complications, or myocardial infarction, was assessed after 1 year. In this TAVI cohort, inappropriate DOAC dosing was observed in 20.6% of patients. Inappropriate DOAC dosage was related to female gender (adj. odds ratio [OR] 2.72, 95% confidence interval [CI] 1.64-4.51, p < 0.001) as well as lower estimated glomerular filtration rate (eGFR) (adj. OR 0.99, 95% CI 0.98-1.00, p = 0.019), and to the administration of non-rivaroxaban DOACs (adj. OR 0.28, 95% CI 0.16-0.50, p < 0.001). After 1 year, patients on both appropriate and inappropriate DOAC dosage exhibited comparable rates of the composite endpoint (OR 0.88, 95% CI 0.53-1.46, p = 0.622). Old age (adj. OR 1.05, 95% CI 1.01-1.10, p = 0.018) as well as anemia (adj. OR 0.86, 95% CI 0.75-0.99, p = 0.031) emerged as independent predictors of the composite endpoint. In this TAVI cohort, female gender and renal insufficiency were associated with inappropriate DOAC dosage, whereas rivaroxaban was linked to appropriate dosing. Inadequate DOAC dosage did not translate into a worse outcome in our TAVI population. Prospective Segeberg TAVI Registry (ClinicalTrials.gov identifier: NCT03192774).

Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF

Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH

Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is a common reason to choose non-recommended (non-rec) doses of non-vitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation (AF); however, it is not known how this practice affects stroke and bleeding outcomes. Purpose To assess clinical outcomes in frail patients with AF receiving non-rec vs recommended (rec) doses of edoxaban using 4-yr follow-up data from ETNA-AF-Europe. Methods The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 yrs. In ETNA-AF-Europe, perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a simplified adaptation of the Rockwood’s Frailty Index. For objective frailty, patients with missing index were categorised as non-frail. Patients with perceived or objective frailty were combined for this analysis. Baseline characteristics and hazard ratios (HRs) with 95% confidence intervals (CIs) assessing risk of outcomes in frail patients prescribed non-rec vs rec edoxaban doses (i.e., non-rec 60mg vs rec 30mg and non-rec 30mg vs rec 60mg) are presented. Data were adjusted for age, sex, and derived versions of the CHA2DS2-VASc and HAS-BLED scores. Net clinical benefit was defined as any stroke/systemic embolic event (SEE), transient ischaemic attack, venous thromboembolic event, major bleeding, or cardiovascular death, whichever came first. Results Of 13164 patients, 1786 were frail (13.6%; perceived frailty [n=1410], age [IQR]: 82.0 [78.0-86.0] yrs, women: 57.9%; objective frailty [n=540], age [IQR]: 77.0 [71.0-82.0] yrs, women: 31.9%; both, n=164). Baseline characteristics are reported in Table 1. Risk of all-cause death was higher in frail patients treated with non-rec 30mg vs rec 60mg (HR [95% CI]: 1.44 [1.06,1.96]). The annualised rate [CI] of any stroke/SEE was non-significantly higher (HR [95% CI]:1.60 [0.80,3.20]) with non-rec 30mg (n=169; 2.25 [1.25,4.06]) vs rec 60mg (n=622; 1.54 [1.08,2.20]). There was, however, no association between treatment received and risk (HR [95% CI]) of major bleeding (1.19 [0.58,2.43]) or net clinical benefit (1.26 [0.84,1.87]) (Figure 1). In frail patients who received non-rec 60mg (n=183) vs rec 30mg (n=695), risk of any stroke/SEE (HR [95% CI]) was higher (2.15 [1.03,4.49]), but there were no significant differences in the risk (HR [95% CI]) of major bleeding (1.03 [0.52,2.01]), net clinical benefit (1.15 [0.78,1.71]), or all-cause death (0.79 [0.59,1.05]) (Figure 1). Conclusions In this large European AF registry, the presence of frailty should not drive dosing recommendations for edoxaban. In particular, when compared with the rec 60mg dose, the non-rec 30mg (reduced) dose, was associated with more all-cause death and no benefits on major bleeding.Baseline Characteristics

Inappropriate dosing of direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Underdose (inappropriate low-dose) of direct oral anticoagulants (DOAC) is sometimes prescribed due to concerns of bleeding risk in patients with atrial fibrillation (AF). In AF patients with coronary artery disease requiring percutaneous coronary intervention (PCI), careful treatment is required to prevent bleeding events because of intensive antithrombotic therapy with a combination of oral anticoagulants and antiplatelet agents. Purpose The purpose of this study was to investigate the prevalence of underdose of DOAC and its impact on clinical outcomes in AF patients with coronary artery disease undergoing PCI. Methods This multicenter observational cohort study enrolled patients with AF on DOAC undergoing PCI between January 2015 and March 2021 at 15 institutions. Appropriateness of DOAC dose was determined according to the manufacturer's labeling recommendations in Japan. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE), all-cause mortality, ischemic stroke, and major bleeding events, were evaluated. Results Of 630 patients enrolled, 168 patients (26.7%) received underdose, 227 (36.0%) received appropriate low-dose, 213 (33.8%) received appropriate standard-dose, and 22 (3.5%) received overdose. Because of the extremely small number of patients in the overdose group, the primary analysis of the present study was a comparison between the underdose group (n=168) and the appropriate dose group (appropriate low-dose and standard-dose groups) (n=440). Although the incidence of MACE, all-cause mortality, and major bleeding events was not significantly different between the 2 groups (log-rank p=0.872, p=0.170, and p=0.725), ischemic stroke more frequently occurred in the underdose group compared with the appropriate dose group (log-rank p=0.010) (Figure 1). The multivariable Cox regression analysis determined underdose of DOAC as an independent predictor for ischemic stroke (adjusted HR 3.288, 95% CI: 1.189-9.088, p=0.022). Conclusions Compared with appropriate dose of DOAC, underdose was associated with a higher incidence of ischemic stroke, despite no significant difference in MACE, all-cause mortality, and major bleeding events, in AF patients undergoing PCI.Figure 1

Use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation across five stages of chronic kidney diseases

Abstract Background Although non-vitamin K antagonist oral anticoagulants (NOACs) were more and more commonly prescribed in the daily practice, data about the use of NOACs in atrial fibrillation (AF) patients with stage 4 and 5 chronic kidney diseases (CKD) are limited. In the present study, we compared the clinical outcomes of AF patients receiving NOACs and those receiving warfarin or non-OACs in different stages of CKD. Methods A total of 39217 AF patients aged &amp;gt;20 years whose data about creatinine clearance (CCr) were available were identified from the electronic health record database of a multi-center healthcare system in Taiwan. Patients were categorized into stage 1 to stage 5 CKDs, and the composite risks of ischemic stroke/systemic embolism, major bleeding and mortality were compared between non-OACs, warfarin and NOACs. Results Around 12.7% and 9.4% of study patients had a stage 4 and stage 5 CKD, respectively. Compared to non-OACs, the use of OACs (either warfarin or NOACs) were consistently associated with a lower risk of composite events from stage 1 to stage 4 CKD, but not for stage 5 CKD (warfarin: aHR 0.912, 95%CI 0.742-1.121; NOACs: aHR 0.993, 95%CI 0.653-1.537)(Figure 1). Compared to warfarin, NOACs were associated with a lower risk of adverse events for patients with stage 2 (aHR 0.630), stage 3 (aHR 0.712) and stage 4 CKD (aHR 0.749). However, the risk did not differ between warfarin and NOACs for stage 1 and stage 5 CKD (Figure 2). Conclusions Although data of the clinical trials for AF patients with stage 4 CKD were relatively lacking, NOACs should still be considered for this AF population. More data are necessary to guide optimal stroke prevention strategy for patients with stage 5 CKD.

Risk factors for non-adherence to oral anticoagulant therapy and the potential of their modification in patients with atrial fibrillation: a narrative literature review

Medication adherence is a key factor of effective stroke prevention in patients with atrial fibrillation receiving oral anticoagulant therapy. At the same time, patient compliance can significantly decrease over time, which leads to an increased thromboembolism risk. A number of studies have shown that a large number of patients receiving anticoagulant therapy are insufficiently adherent to therapy (according to various sources, from 30 to 50% of patients do not comply with the prescribed treatment regimen or interrupt therapy).Independent risk factors for non-compliance include younger age, old age, prior stroke, male sex, multimorbidity, polypharmacy. The risk of decreased compliance with double drug intake compared to single one is noted separately.The review aim is to study the risk factors for non-adherence to oral anticoagulants in patients with atrial fibrillation and possible measures for its prevention.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Commentary on the ANNEXA-I trial from the guideline group of the European Society of Anaesthesiology and Intensive Care (ESAIC) on the reversal of direct oral anticoagulants in patients with life threatening bleeding.

Application of Alfalfa App in the management of oral anticoagulation in patients with atrial fibrillation: a multicenter randomized controlled trial

BackgroundIn recent years, mobile medical technology has made great progress in chronic disease management, but its application in patients with atrial fibrillation (AF) still needs to be clarified.ObjectiveThis study aims to determine whether the newly developed smartphone app for patients with AF (Alfalfa App) can improve anticoagulation knowledge, drug treatment compliance, and satisfaction of AF patients.MethodsAlfalfa App integrates the functions of patient education, remote consultation, and medication reminder through a simple user interface. From June 2020 to December 2020, patients with AF were recruited in five large tertiary hospitals in China. Patients were randomly divided into the Alfalfa App or routine nursing groups. Patients’ knowledge, medication adherence, and satisfaction with anticoagulation were assessed using validated questionnaires at baseline, 1 month, and 3 months.ResultsIn this randomized controlled trial, 113 patients with AF were included, 57 patients were randomly assigned to the Alfalfa App group, and 56 patients were randomly assigned to the routine nursing group. Forty-eight patients in the Alfalfa App group completed a three-month follow-up, and 48 patients in the routine nursing group completed a three-month follow-up. Basic demographic data were comparable between the two groups. The average age of AF patients was 61.65 ± 11.01 years old, and 61.5% of them were male. With time (baseline to 3 months), the knowledge scores of the Alfalfa App group (P<.001) and the routine nursing group (P = .002) were significantly improved, the compliance scores of the routine nursing group(P<.001) and Alfalfa App group(P<.001) significantly improved. Compared with the routine nursing group, patients’ knowledge level and medication compliance using the Alfalfa App at 1 month and 3 months were significantly higher (all P < .05). There were significant differences in knowledge and compliance scores between the two groups with time (all P < .05). The satisfaction degree of drug treatment in the Alfalfa App group was significantly better than that in the routine nursing group (all P < .05).ConclusionsAlfalfa App significantly improved the anticoagulation knowledge, drug treatment compliance, and satisfaction of AF patients. In oral anticoagulation management for AF patients, mobile medical technology that integrates the functions of patient education, remote consultation, and medication reminder may be helpful.Trial registrationRegistration number, ChiCTR1900024455. Registered on July 12, 2019.

Comparative Safety and Effectiveness of Heparin vs. Direct Oral Anticoagulants in Patients with Cirrhosis and ESKD

Comparative Safety and Effectiveness of Heparin vs. Direct Oral Anticoagulants in Patients with Cirrhosis and ESKD

A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease

BackgroundPatients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. MethodsThis is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1–4 weeks, 1–6 months, 6–12 months, >1 year after start of DOAC. ResultsEleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. ConclusionsWe propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non‐valvular atrial fibrillation in Japan

AbstractAimsThere are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non‐valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan.MethodsThis retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest‐neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE).ResultsAfter PS matching, 2955 DOAC‐ and 1603 warfarin‐treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β‐blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50–1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78–1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47–0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22–3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10–3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05–4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22–2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24–2.83).ConclusionsDOAC‐treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin‐treated patients. Prior stroke was shown to augment stroke risk by approximately three‐fold. This large real‐world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

Assessing methods to ascertain persistence and adherence of oral anticoagulants in patients with atrial fibrillation

BackgroundPersistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates. MethodsWe conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: 1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); 2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5 to 60 days) and secondarily, 3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval. ResultsWe identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2 to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4 to 60.7% at one year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5 to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3 to 42.4% for all OACs. Apixaban users had the highest PDC (74 to 75%) over the 365 days, compared to other OACs (60 to 69%). ConclusionsWe found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.

Oral anticoagulation in patients with left ventricular thrombus: a systematic review and network meta-analysis with reconstructed time-to-event data

Oral anticoagulation in patients with left ventricular thrombus: a systematic review and network meta-analysis with reconstructed time-to-event data