Direct-acting Oral Anticoagulants Research Articles

Use of direct-acting anticoagulants (DOACs) delays surgery and is associated with increased mortality in hip fracture patients.

Treatment with direct-acting oral anticoagulants (DOACs) is increasing among hip-fracture patients, with accompanying safety concerns regarding spinal anesthesia (SA). The aim of this study was to investigate if DOAC use is associated with increased waiting time before surgery, increased mortality, or other adverse events. Registry data on surgically treated hip-fracture cases at a single hospital between 2015 and 2021 were analyzed. Multivariable regression analyses were performed with DOAC-status and choice of anesthesia as exposures, and waiting time, length of stay, transfusion, and mortality as outcomes. 2885 cases were included, 467 patients (16%) were using DOACs. DOAC users were older (86.3 vs. 82.2years, p < 0.001), had a higher Charlson Comorbidity Index (2.1 vs. 1.5, p < 0.001) and had longer median time to surgery than non-DOAC cases (36h vs 17h, p < 0.001). General anesthesia (GA) was used in 19.3% of DOAC patients and in 3.0% of non-DOAC patients. DOAC-patients had an increased risk of one-month mortality (Adjusted Odds Ratio (AOR) 1.6 (1.1-2.3)) and one-year mortality (AOR 1.4 (1.1-1.8)). There were no differences in risk of blood transfusion. Patients on DOAC operated under GA had a lower risk of one-year mortality (AOR 0.5 (0.3-0.9)), but a similar one-month mortality to DOAC-patients operated under SA. DOAC users had a longer waiting time to surgery, indicating postponement of surgery due to concerns of the safety of SA. The clinical practice should be changed to allow earlier surgery for DOAC patients.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry.

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.

Comparison of Effectiveness and Safety of Direct-Acting Oral Anticoagulants and Vitamin K Agonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

The objective of the study is mentioned, but it could be further clarified by explicitly stating the aim to compare the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) specifically in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD).We conducted a thorough electronic search of the literature, encompassing databases such as PubMed, EMBASE, Cochrane Library, and Web of Science from their inception up to March 5, 2024. Furthermore, we meticulously examined the bibliographies of included studies to identify additional relevant literature. The reporting of this meta-analysis adhered to the guidelines outlined in the Preferred Reporting of Systematic Review and Meta-analysisguidelines. The endpoints evaluated in this meta-analysis included all-cause mortality, stroke or systemic embolism, and major bleeding. Data analysis was carried out utilizing RevMan Version 5.4 (Cochrane, London, United Kingdom). Dichotomous outcomes, including all-cause mortality, stroke or systemic embolism, and major bleeding, were presented as risk ratios (RRs) with corresponding 95% confidence intervals (CI). A total of 11 studies were incorporated in this meta-analysis, comprising a pooled sample size of 44,863 participants with AF. The pooled analysis revealed no significant disparity between DOACs and VKAs concerning stroke or systemic embolism (RR: 0.93, 95% CI: 0.77 to 1.14) and all-cause mortality (RR: 0.86, 95% CI: 0.74 to 1.00). However, there was a noteworthy reduction in the risk of major bleeding events associated with DOACs compared to VKAs (RR: 0.84, 95% CI: 0.73 to 0.96). Consequently, DOACs may be considered a viable alternative to warfarin in patients with ESRD. However, we need further larger clinical trials to validate these findings.

Effective application of a direct-acting oral anticoagulants reversal agent in acute type A aortic dissection repair: A case report

There are insufficient reports on the use of andexanet alfa in cardiac surgery. A 67-year-old man was diagnosed with type A aortic dissection and performed emergent surgery. His medical history included atrial fibrillation treated with Edoxaban. We performed total arch replacement. Despite administration of enough protamine, fresh frozen plasma, and platelet administration, controlling bleeding was difficult. Thus, Andexanet Alfa was initiated after CPB withdrawal. Surgical bleeding was dramatically controlled after its administration. There were no findings suggestive of an embolic event. In conclusion, administration of Andexanet Alfa is safe after cardiopulmonary bypass withdrawal.

Abstract 98: Direct-Acting Oral Anticoagulants and Antiseizure Medications for Atrial Fibrillation and Epilepsy: Risk of Thromboembolic and Major Bleeding Events

Rationale: Direct-acting oral anticoagulants (DOACs) are commonly prescribed with antiseizure medications (ASMs) due to concurrency and causal links between atrial fibrillation (AF) and epilepsy. However, enzyme-inducing-ASMs (EI-ASMs) may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk. Methods: We leveraged large-scale healthcare data to conduct an emulated target trial among a nationally representative cohort with AF and epilepsy. Thromboembolic and bleeding event rates were contrasted between adults on DOACs + EI-ASMs versus active comparators on DOACs + non-enzyme inducing ASMs. Data-adaptive high-dimensional propensity score matching was employed to control for observed confounders and proxies for unobserved confounders. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs. Results: Among incident ASM + DOAC users, we identified 14,078 and 14,158 episodes that met eligibility criteria for assessment of thromboembolic and bleeding outcomes, respectively. Incidence per 1,000 person-years was 88.5 for thromboembolic events and 68.3 for major bleeding events. Compared with use of non-enzyme inducing ASMs, use of EI-ASMs with DOACs was not associated with a difference in thromboembolic events (aHR=1.10, 95% CI: 0.82-1.46), but was associated with a reduction in major bleeding events (aHR=0.63, 95% CI: 0.44-0.89). Conclusions: EI-ASMs were not associated with alteration in DOAC efficacy. These real-world data are reassuring for the care of adults with epilepsy who require anticoagulation, particularly across a larger global community where EI-ASMs remain mainstays. Further research is needed on the reduction in bleeding risk with EI-ASMs, as this may be suggestive of pharmacokinetic interactions lowering DOAC levels without negating therapeutic effects.

Safety of direct-acting oral anticoagulant (DOAC) prescribing: OpenSAFELY-TPP analysis of 20.5 million adults' electronic health records.

During the COVID-19 pandemic many patients were switched from warfarin to DOACs which require the creatinine clearance calculated to ensure the correct dose is prescribed to avoid bleeding or reduced efficacy. To identify the study population proportion prescribed a DOAC. Of these, the proportion with recorded: weight, estimated Glomerular Filtration Rate (eGFR), creatinine, creatinine clearance (CrCl) and atrial fibrillation (AF). To analyse the proportion of patients with recorded AF and CrCl prescribed a recommended DOAC dose. A retrospective cohort study of 20.5 million adult NHS patients' electronic health records (EHRs) in England in the OpenSAFELY-TPP platform (January 2018 to February 2023). Patients on DOACs were analysed for age, sex, recorded weight, eGFR, creatinine, CrCl and AF. Prescribed DOAC doses in patients with recorded AF were compared to recommended doses for recorded CrCl and determined as either recommended, underdose or overdose. In February 2023, weight, eGFR, creatinine, CrCl, AF and, AF and CrCl were recorded in 72.8%; 92.4%; 94.3%; 73.5%; 73.9% of study population respectively. Both AF and CrCl were recorded for 56.7% of patients. Of these, 86.2% received the recommended and 13.8% non-recommended DOAC doses. CrCl is not recorded for a substantial number of patients on DOACs. We recommend that national organisations tasked with safety, collectively update guidance on the appropriate weight to use in the Cockcroft-Gault equation, clarify that CrCl is not equivalent to eGFR and work with GP clinical system suppliers to standardise the calculation of CrCl in the EHR.

Abstract WP169: Thromboelastography as a Biomarker of Emergent Direct-Acting Oral Anticoagulant Reversal With Prothrombin Complex Concentrates for Intracranial Hemorrhage

Prothrombin complex concentrates (PCCs) are used to emergently reverse direct-acting oral anticoagulant (DOAC) activity. PCCs are recommended as an alternative to recombinant coagulation factor-Xa to reverse anticoagulation activity of apixaban or rivaroxaban. Measuring the degree of anticoagulation reversal in this population is limited. Thromboelastography (TEG) has been used to detect the presence of DOAC plasma levels in patients chronically taking a DOAC but has not been utilized to measure the effect on anticoagulant activity after PCC administration. We aimed to determine whether TEG R-time is useful in detecting the impact of PCC administration on anticoagulation activity in patients with anti-factor Xa-associated intracranial hemorrhage (ICH). We prospectively evaluated the utility of TEG to assess anticoagulation activity after factor Xa inhibitor reversal with 4-factor PCC. Adults with ICH taking apixaban or rivaroxaban were included. Patients were excluded if their last known dose of anticoagulation was &gt;48 hours prior to arrival, had known apixaban or rivaroxaban blood levels &lt;20 ng/mL, or had the following comorbidities: hepatic failure, hereditary disorders of hemostasis, polytrauma, or pregnancy. TEG samples were collected before PCC administration (if available), and 0.5, 12, and 24 hours after PCC administration. Thirty-one patients were enrolled between November 2022 and August 2023. The median PCC dose was 24.5 units/kg (IQR 20.3-26.9 units/kg; n=29). Nine patients received anticoagulation reversal after baseline TEG collection; the remainder received anticoagulation reversal at transferring facilities. Baseline R-time was negatively correlated with time since last dose of DOAC (n=9). A median decrease in R-time of 0.8 minutes after PCC (IQR -1.6 - 0.3; n=8) was found in patients with baseline TEG collection. R-time rebounded by a median of 0.75 minutes (IQR 0.2-2.0; n=8) from 0.5 hours to 12 hours after PCC administration (n=8). TEG R-time, a measure that inversely correlates with the degree of anticoagulant effect, rapidly decreases after PCC in patients taking DOACs that present with acute ICH. TEG R-time rebounds 12 hours after PCC administration. TEG-R time may be a useful biomarker in DOAC reversal with PCC.

Comparative safety and effectiveness of reduced doses of direct acting oral anticoagulants for stroke prevention in atrial fibrillation.

This Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in non-valvular atrial fibrillation. The study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011, to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage. The meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72). In this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects ofwarfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Assessment and predictors of inappropriate dose of direct oral anticoagulants

Direct-Acting Oral Anticoagulants (DOACs) have revolutionized the management of Atrial Fibrillation (AF) and Venous Thromboembolism (VTE). However, recent audits reveal a significant burden of inappropriate dosages in the prescribing of direct-acting oral anticoagulants. Our aim is to identify the prevalence and predictors of such inappropriate dosing in our patients. This retrospective study was conducted from June 2016 to January 2018. Patients who received dabigatran, rivaroxaban, or apixaban for treatment of venous thromboembolism or atrial fibrillation were included. Appropriateness of direct-acting oral anticoagulants dosing was assessed using US Food and Drug Administration guidelines. Data was analyzed using IBM® SPSS Version 26. 337 patients were included, with a mean age of 62.9±18.7 years. The majority were female (196, 58.3%). Of the patients, 194 (57.6%) received apixaban, 99 (29.4%) received rivaroxaban, and 44 (13.1%) received dabigatran. A total of 242 (71.8%) patients were prescribed direct-acting oral anticoagulants appropriately. Under-dosing and over-dosing were identified in 74 (22%) and 21 (6.2%) patients, respectively. Predictors of inappropriate dosing were age greater than 75 years (OR: 2.76, 95% CI: 1.67-4.56, p&lt;0.001) and creatinine clearance less than 50 ml/minute (OR: 0.38, 95% CI: 0.19-0.74, p: 0.005). Inappropriate dosing was significantly associated with mortality (p=0.010).One-third of our patients received an inappropriate dose of direct-acting oral anticoagulants, mostly from underdosing. Elderly age and low creatinine clearance are significant predictors of inappropriate dose administration.

Direct-Acting Oral Anticoagulants in patients at extremes of body weight: a review of pharmacological considerations and clinical implications.

Patients at extremes of body weight are underrepresented in randomized controlled trials of direct-acting oral anticoagulants (DOACs). Therefore, their optimal anticoagulant treatment remains a topic of debate. The aim of this narrative review is to summarize the evidence on the pharmacokinetic and pharmacodynamic profile of DOACs for treating patients at extremes of body weight in venous thromboembolism (VTE) and in the prevention of cardioembolic stroke in nonvalvular atrial fibrillation (NVAF). A literature search was conducted in the main bibliographic databases, and the most relevant reviews and original articles on the topic were selected. Although data in these patient groups are limited, apixaban and rivaroxaban show a favorable pharmacokinetic and pharmacodynamic profile in obese VTE treatment and NVAF patients and, in the case of apixaban, also in underweight patients. In particular, these drugs demonstrated comparable efficacy and safety to standard therapy. Very few data were available for dabigatran and edoxaban; the latter drug was safer at a lower dose, mainly in underweight patients. Our findings are in line with the last International Society of Haemostasis and Thrombosis position paper and European Heart Rhythm Association 2021 practical guide, suggesting the use of apixaban and rivaroxaban in morbidly obese patients (>120 kg or body mass index ≥40 kg/m 2 ) and the reduced dosage of edoxaban in low-weight patients. Future studies should focus on large populations of patients at extremes of body weights to acquire more clinical and pharmacokinetic evidence on all available DOACs, especially those currently less investigated.

A Case of Dabigatran-related Nephropathy Complicated by Tubulointerstitial Nephritis in a Patient with a Normal Renal Function and Undiagnosed IgA Nephropathy.

A 69-year-old woman was referred to our hospital because of an acute kidney injury with macroscopic hematuria. She had been taking dabigatran for atrial flutter for six years. Based on the typical histological findings of her kidney biopsy and her history of dabigatran use with prolonged activated partial thromboplastin time, she was diagnosed with dabigatran-related nephropathy complicated by tubulointerstitial nephritis with IgA nephropathy. After prednisolone therapy, the renal function improved. Direct-acting oral anticoagulants, including dabigatran, may cause anticoagulant-related nephropathy similar to warfarin, even in patients with a normal renal function. Tubulointerstitial nephritis may coexist with dabigatran-related nephropathy, and prednisolone therapy should be considered in such cases. IgA nephropathy has been reported as a background disease, and caution should be exercised when encountering it.

Pulmonary Infarction Due to Direct-acting Oral Anticoagulant Malabsorption

A man in his 50s with a history of sleeve gastrectomy and rivaroxaban use for multiple venous thromboembolic events presented with subacute progressive cough. Axial images of a computerized tomography (CT) scan of the chest showed ground glass and consolidations within the right middle and right lower lobes, and he was treated for presumed community-acquired pneumonia. Given continued symptoms despite 7 days of antibiotics, his CT images were re-reviewed. Wedge shaped airspace disease more recognizable in sagittal views prompted concern for pulmonary infarction, and acquisition of a contrast-enhanced chest CT revealed interval increase of a prior pulmonary embolism and findings of acute on chronic thrombosis. Given the patient was adherent to rivaroxaban and had a negative hypercoagulable work-up, rivaroxaban malabsorption related to the patient’s sleeve gastrectomy was invoked as the cause of anticoagulant failure, and the patient was successfully transitioned to warfarin therapy, highlighting malabsorption as a cause of recurrent VTE in patients who have received bariatric surgery and who take direct-acting oral anticoagulants.

Risk of Major Bleeding Associated with Concomitant Direct-Acting Oral Anticoagulant and Clopidogrel Use: A Retrospective Cohort Study.

Combined anticoagulant-antiplatelet therapy is often indicated in adults with cardiovascular disease and atrial fibrillation or venous thromboembolism. The study aim was to assess the comparative risk of bleeding between rivaroxaban and apixaban when combined with clopidogrel. We conducted a retrospective cohort study of commercially insured US adults newly treated with a combination of rivaroxaban+clopidogrel or apixaban+clopidogrel (2015-2018) using Merative™ Marketscan Research Databases. We used propensity score-based inverse probability of treatment weighting (IPTW) to balance the treatment groups. Weighted Cox proportional hazards regression was used to estimate the risk of major bleeding. The study cohort included 2895 rivaroxaban+clopidogrel users and 3628 apixaban+clopidogrel users. The median (range) duration of follow up was 61 (73) days. Rivaroxaban+clopidogrel users had a similar risk of major bleeding compared with apixaban+clopidogrel users (IPTW incidence rate per 100 person-years 7.96 vs 7.38; IPTW hazard ratio [HR] 1.13 [95% CI 0.78-1.63]). In the subcohort of adults who were treated with DOAC or clopidogrel monotherapy prior to the combined therapy, the risk of major bleeding did not differ by the drug of monotherapy (IPTW HR for rivaroxaban+clopidogrel group: 0.66 [95% CI 0.33-1.32]; IPTW HR for apixaban+clopidogrel group: 1.10 [95% CI 0.55-2.23]) CONCLUSIONS: In our study of commercially insured US adults, the concomitant use of rivaroxaban+clopidogrel and apixaban+clopidogrel conferred a similar risk of major bleeding. DOAC versus clopidogrel monotherapy prior to the concomitant therapy did not influence the risk of major bleeding.

Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies.

Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE. We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively. Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57-1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61-0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61-0.92, I2 = 50%; RR 0.58, 95% CI 0.50-0.67, I2 = 7%; RR 0.64, 95% CI 0.59-0.70, I2 = 0%, respectively). Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.

Antithrombotic therapy in patients after transcatheter aortic valve implantation: a network meta-analysis

Abstract Aims The optimal antithrombotic therapy to balance the risk of thrombosis and bleeding in patients who undergo transcatheter aortic valve implantation (TAVI) is unknown. This systematic review/network meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of different oral anticoagulant (OAC) and antiplatelet regimens in patients post-TAVI. Methods and results MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched from inception to April 2023. Co-primary outcomes were all-cause death and major bleeding. We conducted Bayesian network meta-analyses to compare all interventions simultaneously. For each outcome, we generated odds ratios (ORs) with 95% credible intervals using a random-effects model with informative priors, and ranked interventions based on mean surface under the cumulative ranking curve. We included 11 RCTs (n = 6415), including 1 unpublished RCT. Three trials enrolled patients with an indication for an OAC. Overall risk of bias was low or with some concerns. Median age was 81 years. Median follow-up was 6 months. The combination of OAC plus single antiplatelet therapy (SAPT) increased the risk of all-cause death compared with dual antiplatelet therapy (DAPT) (OR 1.78, 95% credible interval 1.15–2.77). No other comparisons for all-cause death were significantly different. For major bleeding, SAPT reduced the risk compared with DAPT, direct-acting OAC, and OAC + SAPT (OR 0.20–0.40), and DAPT reduced the risk compared with OAC + SAPT. SAPT and DAPT ranked best for all-cause death, while SAPT ranked best for major bleeding. Conclusion In post-TAVI patients, SAPT may provide the optimal balance of reducing thrombotic events while minimizing the risk of bleeding.

Stroke and Bleeding Risks of Endocardial Ablation for Ventricular Arrhythmias

BackgroundRisks of radiofrequency catheter ablation for ventricular arrhythmias include emboli and bleeding complications but data on antithrombotic regimens are limited and guidelines do not specify a systematic approach. ObjectivesThis study sought to assess embolic and bleeding complications in relation to pre-periprocedure and post-periprocedure antithrombotic regimens. MethodsProspective assessment for complications was performed for 663 endocardial radiofrequency catheter ablation procedures in 616 consecutive patients (median age 64 years [Q1-Q3: 54-73 years], 70.3% men, 71.6% with cardiomyopathy, 44.5% with sustained ventricular tachycardia). ResultsThere were 2 strokes (0.3%; 95% CI: 0.0%-0.8%), 1 transient ischemic attack (0.15%), and 2 pulmonary emboli (0.3%). There were 39 bleeding complications (5.9%) including 11 pericardial effusions (1.7%), and 28 related to vascular access (4.2%). Consistent with the prevalence of coronary artery disease (47.5%), atrial fibrillation (30.0%), and prior stroke (10.6%), preprocedure, 464 patients (70.0%) were taking antithrombotic agents including 220 (33.2%) taking aspirin alone (ASA), and 163 (24.6%) taking warfarin or a direct acting oral anticoagulant (DOAC). Preprocedure non-ASA antiplatelet use (OR: 2.846; P = 0.011) and DOAC use (OR: 2.585; P = 0.032) were associated with risk of bleeding complications. Following ablation, 49.8% of patients were treated with ASA 325 mg/d and 30.3% received DOACs or warfarin. New DOAC or warfarin administration was initiated in only 6.6% of patients. Overall, 39.7% of patients continued the same preprocedure antithrombotic regimen. ConclusionsStroke is a rare complication of radiofrequency catheter ablation for ventricular arrhythmia using ASA 325 mg/d as a minimal postprocedure regimen with more potent regimens for selected patients.

Real life results of direct-acting oral anticoagulants recommended-dose in obese vs normal-weight patients with venous thromboembolism

BackgroundThere is scarce evidence on the effectiveness and safety of recommended-dose direct acting oral anticoagulants (DOACs) in obese patients with venous thromboembolism (VTE). Material and methodsWe used the data in the RIETE registry to compare the rates of VTE recurrences and major bleeding during long-term therapy with DOACs at recommended doses in patients with body mass index ≥30 kg/m2 (obese) vs. those with BMI 18.5–24.9 kg/m2 (normal weight). We performed regression models with competing risks for death. ResultsFrom January 2013 through October 2022, 2885 obese patients and 2676 with normal weight in RIETE received rivaroxaban (n = 3020), apixaban (n = 1754), edoxaban (n = 636) or dabigatran (n = 151). Median age was 63 years and 52 % were female. At baseline, obese patients were more likely to have diabetes (18.6 % vs. 8.4 %), hypertension (51.9 % vs. 31.4 %) or pulmonary embolism (67.7 % vs. 61 %), and less likely to have renal insufficiency (5.3 % vs. 16 %) or anaemia (21.8 % vs. 28 %%). During anticoagulation (median, 147 vs. 101 days), the obese had a similar rate of VTE recurrences (1.71 vs. 2.14 events per 100 patients-years; hazard ratio (HR): 0.81; 95 % CI: 0.49–1.34) or major bleeding (1.45 vs. 1.76 per 100 patients-years; HR: 0.91; 95 % CI: 0.52–1.59) than those with normal weight. These findings persisted after multivariable analysis (recurrent VTE, HR: 0.80; 95 % CI: 0.48–1.32; major bleeding, HR: 1.11; 95 % CI: 0.60–2.07). ConclusionThe use of DOACs at recommended doses in obese patients with VTE was associated with similar rates of VTE recurrences or major bleeding than in patients with normal weight.

Analysis of the therapeutic effect and application of anticoagulant drugs

As the global population ages, the incidence of cardiovascular disease, stroke, and other diseases associated with thrombosis is also increasing, resulting in a great need for effective anticoagulant treatments. The purpose of this research is to summarize the development of anticoagulant drugs to date, including their drug types, version iterations, mechanisms of action, as well as current challenges and future development directions of anticoagulant drugs. The research will first review traditional anticoagulants, such as vitamin K antagonists and heparins, and discuss in detail their effects, advantages, and limitations. Next, it will give a detailed description of new anticoagulants, such as direct acting oral anticoagulants (DOACs), and analyse their advantages over traditional anticoagulants in terms of safety and efficacy. Finally, it will propose the strategy of individualized therapy for specific population and the combination therapy of anticoagulant therapy and other drugs, and look forward to the development of new anticoagulant drugs in the future. The application of anticoagulant drugs in medicine has a wide range of clinical significance. With the continuous deepening of research, new therapeutic strategies and drugs are constantly being developed and improved, aiming at providing more safe and effective anticoagulant therapy.

Adoption of new medicines in primary care: A comparison between the uptake of new oral anticoagulants and diabetes medicines.

To gain insight in the uptake and practice variation in the prescription of 2 new medicine groups for common conditions in primary care (direct-acting oral anticoagulants [DOACs] and incretin-based therapies) from introduction, around 2007, to 2019 and the correlation between the adoption of those medicines in primary care. Prescription data from general practices in the Dutch Nivel Primary Care Database from 2007 to 2019 were used. The percentage of patients with prescriptions for DOACs of all patients with prescriptions for DOACs and vitamin K antagonists was calculated per practice per year, as was the percentage of patients prescribed incretin-based therapies as a proportion of all patients with diabetes medication. Multilevel models were used to estimate practice variation for DOACs and incretin-based therapies, expressed as intraclass correlation coefficients. Linear regression analysis was used to study the association between the prescription of DOACs and incretin-based therapies. Per year, 46-424 general practices and 179 933-1654 376 patients were included. In 2019, the mean percentage of patients per practice using DOACs or incretin-based therapies was 54.9 and 9.7%, respectively. The intraclass correlation coefficient decreased from 0.75 to 0.024 for DOACs and from 0.33 to 0.074 for incretin-based medicines during the study period. No clear correlation was found between the prescription of DOACs and incretin-based therapies. DOACs and incretin-based therapies have different adoption profiles and practice variation is large, especially in the years before these medicines were introduced in guidelines. Early adopters of both medicine classes differ.