Vitamin K Antagonists In Patients Research Articles

Clinical Features, Management, and Recurrence of Acute Ischemic Stroke Occurring in Patients on Oral Anticoagulant Treatment for Nonvalvular Atrial Fibrillation: A Real-World Retrospective Study.

The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF). We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded. A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P =0.358; 92.3% vs. 74.3%, P =0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P =0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences. In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted.

Direct oral anticoagulants exhibit lower risks of mortality and bleeding compared to vitamin-k antagonists in atrial fibrillation patients on chronic hemodialysis: a meta-analysis

Abstract Background Atrial fibrillation (AF) is a common arrhythmia in patients with chronic kidney disease (CKD). Although direct oral anticoagulants (DOACs) are equally or more effective than vitamin K antagonists (VKAs) in patients with moderate CKD, evidence claiming the benefits of DOACs over VKAs in patients on hemodialysis (HD) is scarce. Purpose This meta-analysis aimed to assess the outcomes of patients with AF on chronic HD by comparing the clinical outcomes of DOACs versus VKAs. Methods A systematic literature search was conducted across various databases to retrieve studies focusing on efficacy and safety outcomes in patients with AF on chronic hemodialysis comparing DOACs and VKAs. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel random-effects model in Review Manager 5.4. Statistical significance was set at p <0.05. Results Nine studies with 39, 831 patients were included. The risk of all-cause mortality [RR: 0.73; 95% CI: 0.60, 0.88; p=0.001], major bleeding [RR: 0.63; 95% CI: 0.52, 0.76; p<0.00001], gastrointestinal bleeding [RR: 0.67; 95% CI: 0.53, 0.85; p=0.0009], intracranial hemorrhage [RR: 0.57; 95% CI: 0.38, 0.84; p=0.004], all-cause stroke [RR: 0.64; 95% CI: 0.51, 0.81; p=0.0001], and ischemic stroke [RR: 0.53; 95% CI: 0.29, 0.96; p=0.04] were lower in the DOAC group than in the VKA group. The risk of cardiovascular-related death [RR: 1.34; 95% CI: 0.69, 2.60; p=0.39], and clinically relevant non-major bleeding [RR: 0.90; 95% CI: 0.75, 1.08; p=0.26] showed no significant differences. Conclusion The risks of all-cause stroke, ischemic stroke, all-cause mortality, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage in the patients with AF undergoing chronic HD were lower in the DOAC group than in the VKA group. Further large-scale RCTs are needed to generate more robust evidence through adequately powered studies, leading to conclusive results that are applicable to real-world scenarios.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD). We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH). Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs. NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.

Safety and effectiveness of oral anticoagulants in patients with atrial fibrillation and stage 4 chronic kidney disease: a real-world experience

It is still uncertain whether direct oral anticoagulants (DOACs) perform better than vitamin K antagonists (VKAs) in subjects with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). The aim of the study was to compare safety and effectiveness of DOACs and VKAs in patients with NVAF and stage 4 CKD (creatinine clearance 15–29 mL/min). We searched the hospital databases of two academic centers to retrospectively identify patients with stage 4 CKD who were on treatment with DOACs or VKAs for NVAF. Safety was the primary outcome of the study and was assessed in terms of incidence of major bleeding (MB). Secondary outcomes were clinically relevant non-major bleeding (CRNMB) and death for any cause. A total of 176 patients (102 on DOACs and 74 on VKAs) were found and included in the analysis. The incidence rate of MB was not statistically different between groups (8.6 per 100 patients-year in the DOAC group and 5.6 per 100 patients-year in the VKA group). Rates of IS/SSE and CRNMB were statistically similar in the two treatment groups, as well. There were less deaths for any cause in the DOAC group than in the VKA group (8.6 and 15.8 per 100 patients-year, respectively), but the difference was not statistically significant. This study found no difference in terms of safety and effectiveness between patients with NVAF and stage 4 CKD treated with DOACs and VKAs. Larger prospective or randomized studies are needed to confirm these findings.

Non-vitamin K oral antagonist (NOAC) compared to vitamin K antagonist (VKA) in left ventricular thrombus

ABSTRACT Background: Thromboembolic events are serious left ventricular thrombus (LVT) complications. Despite the limitations of vitamin K antagonist (VKA) drugs, it continues to be the recommended oral anticoagulation for LVT. Recently, nonvitamin K oral antagonist (NOAC) has gained popularity as an off-labeled treatment for systemic embolism prevention in LVT. Objective: In this study, we aim to compare the outcomes (stroke and bleeding) of warfarin versus NOAC therapy in patients with LVT. Methods: This retrospective cohort study compares NOAC and VKA therapy in LVT patients. We enrolled 201 patients with an echocardiography-confirmed LVT from January 2018 to December 2022. Patients who received NOAC therapy (NOAC, n = 77) were compared to VKA patients (VKA, n = 124). The primary endpoint was a composite of stroke, minor and major bleeding. Results: The median follow-up time was 17 months (25th–75th percentiles: 8–38). On unmatched analysis, both groups had no difference in major bleeding (log-rank, P = 0.61) and stroke (log-rank, P = 0.77). However, all bleeding events were higher with NOAC (log-rank, P = 0.01). On matched analysis, there was no difference between both groups in the overall bleeding events (P = 0.08), major bleeding (P = 0.57), and stroke (P = 0.66). Minor bleeding was significantly lower in the VKA group (P = 0.04). Conclusion: In patients with LVT, NOAC was as effective as VKA in stroke prevention without increasing the risk of major bleeding.

The impact of different anticoagulants and antiplatelets regimens on acute epistaxis outcomes

BackgroundThe impact of anticoagulants (AC) and antiplatelets (AP) on the management of acute epistaxis remains unclear. This study investigated the association between AC/AP therapy and treatment outcomes in patients with acute epistaxis.MethodologyA retrospective analysis of patients presented to the otolaryngology emergency room with acute epistaxis (2014–2022). Patients were categorized based on their regular medications: AP, dual AP therapy (DAPT), new oral anticoagulants (NOAC), vitamin K antagonists (VKA), or no regular AC/AP use (control group). Outcome measures included rates of minor interventions (chemical or electrical cautery, nasal tamponade), major interventions (endoscopic ligation, embolization), recurrent emergency department visits, admission rates, and duration.Results786 patients were included with an average follow-up period of 52.56 ± 20.4 months. Compared to the control group, patients on AP, DAPT, or VKA had significantly higher rates of minor interventions (63.1% vs. 74.4%, 79.6%, and 77.3%, respectively, p < 0.05). DAPT users exhibited a higher rate of major interventions than the control (5.6% vs. 1.3%, p = 0.053). NOAC users showed no significant difference in minor interventions compared to control and required no major interventions. Both NOAC and VKA users had significantly higher rates of recurrent epistaxis events and prolonged hospitalization compared to the control (p < 0.01 and p < 0.05, respectively).ConclusionsNOAC demonstrated more favorable outcomes than VKA in patients with acute epistaxis, and DAPT use was associated with an increased need for major interventions. These findings suggest a more conservative approach in NOAC users than other AC/AP agents.

#280 Effectiveness and safety of direct oral anticoagulants vs VKA in patients on chronic dialysis: a target trial emulation using nationwide registry data

Abstract Background and Aims The mortality and morbidity rates among patients on dialysis remain high and cardiovascular disease is the leading cause of death in this population. In chronic kidney disease (CKD), a major thromboembolic risk is paradoxically associated with a major haemorrhagic risk. Hence, the prescription of oral anticoagulants in CKD patients is challenging. Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In an exhaustive French nationwide registry of patients undergoing chronic dialysis, we compared the effectiveness and safety of off-label DOAC use versus approved vitamin K antagonist (VKA). Method Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using target trial emulation design, we compared the safety and effectiveness outcomes for DOAC and VKA using propensity-score-weighted cause-specific Cox regression. Results 8 954 patients received an oral anticoagulant (483 DOAC and 8 471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2 567 patients presented a first thromboembolic event and 1 254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (HR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94] (Figure). A non-significant trend toward lower risk of major bleeding events was found in patients treated with a DOAC compared to patients treated with a VKA (weighted HR [95% CI]: 0.68 [0.41; 1.12]) (Figure). Sensitivity analyses showed the same trends. Conclusion The fact that patients on dialysis are excluded from large, cardiovascular-disease-focused randomized controlled trials (such as those with DOACs) significantly limits the evidence needed to make clinical decisions. Most of the retrospective cohort studies comparing these two drug classes were performed in the USA, where, in contrast to Europe, apixaban has been approved for the treatment of non-valvular fibrillation in patients on haemodialysis. Our real-world study of patients on dialysis is one of the first of its type to have assessed the effectiveness and safety of off-label DOAC prescription (relative to VKA prescription) in Europe. In a large group of dialysis patients initiating oral anticoagulation, the off-label use of DOACs was associated with a statistically significant lower risk of thromboembolic events, and a non-significant trend toward lower risk of bleeding relative to VKA use. These results are reassuring with regard to the off-label use of DOACs and might facilitate the establishment of an expert consensus and guidelines on antithrombotic therapy in patients with ESKD.

Oral anticoagulants versus vitamin K antagonists in the treatment of non-valvular atrial fibrillation in patients with stage 4-5 chronic kidney disease

Aim. To compare the effectiveness and safety of direct oral anticoagulants (DOACs) with a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and stage 4 and 5 chronic kidney disease (CKD).Material and methods. We searched in the PubMed, Google Scholar, and Web of Science databases from 1990 to 2022 for studies that compared DOACs with VKAs in patients with AF and stage 4 and 5 CKD. The patient, intervention, comparison, outcome (PICO) search strategy was used. Data were extracted by independent researchers and meta-analyzed.Results. A total of 6 studies were included in this meta-analysis. In terms of effectiveness, DOACs were comparable to VKAs. In terms of safety, DOACs and VKAs also had no statistical differences in hemorrhagic stroke, minor/gastrointestinal bleeding, overall mortality, but there was statistical significance in major bleeding. Conclusion. In terms of efficacy and safety, in general, DOACs were comparable to VKAs, but there were a number of following differences: the administration of DOACs to patients with stage 4 and 5 CKD, as well as those on hemodialysis, was accompanied by a significant reduction in the number of major bleedings, compared with warfarin therapy.

Relative performance evaluation of four bleeding risk scores in atrial fibrillation patients. What does the new DOAC score provide?

BackgroundRecently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. MethodsWe studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. ResultsThere were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively).Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores.In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. ConclusionsThe new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT04364516

Eventos hemorrágicos tardíos en pacientes de TAVI anticoagulados con antagonistas de la vitamina K o anticoagulantes orales de acción directa

Introduction and objectivesThe optimal chronic antithrombotic regimen for patients with atrial fibrillation undergoing transcatheter aortic valve implantation (TAVI) remains uncertain. Our aim was to compare the incidence of late bleeding events between patients on direct oral anticoagulants (DOACs) and those on vitamin-K antagonists (VKA). MethodsThis single-center observational study included TAVI patients requiring oral anticoagulation at discharge between 2015 and 2021. The primary endpoint was any clinically significant bleeding event. Secondary endpoints were stroke, heart failure, and all-cause mortality. ResultsA total of 702 TAVI procedures were performed, with 297 patients requiring oral anticoagulation at discharge. Among them, 206 (69.4%) received VKA and 91 (30.6%) received DOAC. Baseline clinical, procedural and in-hospital characteristics did not significantly differ between groups, except for better renal function among DOAC patients. The median length of follow-up was 2.8 years. The risk of bleeding events was higher in patients receiving DOACs than in those receiving VKA (HR, 2.27; 95%CI, 1.21-4.26; incidence of 9.7 and 4.2 events per 100 patient-years of follow-up for DOAC and VKA patients, respectively). There were no statistically significant differences in the rates of stroke (HR, 1.28; 95%CI, 0.4-4.3), heart failure hospitalization (HR, 0.92; 95%CI, 0.46-1.86), or all-cause mortality (HR, 1.02; 95%CI, 0.68-1.55). ConclusionsIn older patients undergoing TAVI and receiving anticoagulant therapy for atrial fibrillation, the use of DOAC was associated with a higher risk of late bleeding events than VKA.

Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial

IntroductionAtrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant...

Non–Vitamin K Antagonist Versus Vitamin K Antagonist Oral Anticoagulant Agents After Transcatheter Aortic Valve Replacement

BackgroundStudies comparing long-term outcomes between non–vitamin K antagonist (VKA) oral anticoagulant agents (direct oral anticoagulant agents [DOACs]) and VKA anticoagulant agents after transcatheter aortic valve replacement (TAVR) are scarce, with conflicting results. ObjectivesThe aim of this study was to examine the periprocedural, short-term, and long-term safety and effectiveness of DOACs vs VKAs in patients undergoing TAVR via femoral access with concomitant indications for oral anticoagulation. MethodsConsecutive patients undergoing transfemoral TAVR in the prospective national SwissTAVI Registry between February 2011 and June 2021 were analyzed. Net clinical benefit (a composite of all-cause mortality, myocardial infarction, stroke, and life-threatening or major bleeding) and the primary safety endpoint (a composite of life-threatening and major bleeding) were compared between the VKA and DOAC groups at 30 days, 1 year, and 5 years after TAVR. ResultsAfter 1:1 propensity score matching, 1,454 patients were available for analysis in each group. There was no significant difference in the rate of the net clinical benefit and the safety endpoints between the groups as assessed at 30 days and 1 and 5 years post-TAVR between VKAs and DOACs. VKAs were associated with significantly higher rates of 1- year (HR: 1.28; 95% CI: 1.01-1.62) and 5-year (HR: 1.25; 95% CI: 1.11-1.40) all-cause mortality. Long-term risk for disabling stroke was significantly lower in the VKA group after excluding periprocedural events (HR: 0.64; 95% CI: 0.46-0.90). ConclusionsAt 5 years after TAVR, VKAs are associated with a higher risk for all-cause mortality, a lower risk for disabling stroke, and a similar rate of life-threatening or major bleeding compared with DOACs. (SwissTAVI Registry; NCT01368250)

Safety and efficacy of NOAC vs. VKA in patients treated by PCI: a retrospective study of the FRANCE PCI registry.

Dual antithrombotic therapy (DAT) combining oral anticoagulation (OAC), preferentially Non-vitamin K antagonist OAC (NOAC) and single antiplatelet therapy (SAPT) for a period of 6-12 months is recommended after percutaneous coronary intervention (PCI) in patients with an indication for OAC. To compare outcomes between vitamin K antagonist (VKA) and NOAC-treated patients in the nation-wide France PCI registry. All consecutive patients from the France PCI registry treated by PCI and discharged with OAC between 2014 and 2020 were included and followed one-year. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) classification ≥3 and major adverse cardiac events (MACE) as the composite of all-cause mortality, myocardial infarction (MI), and ischemic stroke. A propensity-score analysis was used. Of the 7,277 eligible participants, 2,432 (33.4%) were discharged on VKA and 4,845 (66.6%) on NOAC. After propensity-score adjustment, one-year major bleeding was less frequent in NOAC vs. VKA-treated participants [3.1% vs. 5.2%, -2.1% (-3.6% to -0.6%), p = 0.005 as well as the rate of MACE [9.2% vs. 11.9%, -2.7% (-5.0% to -0.4%), p = 0.02]. One-year mortality was also significantly decreased in NOAC vs. VKA-treated participants [7.4% vs. 9.9%, -2.6% (-4.7% to -0.5%), p = 0.02]. The area under ROC curves of the anticoagulant treatment propensity score was estimated at 0.93, suggesting potential indication bias. NOAC seems to have a better efficacy and safety profile than VKA. However, potential indication bias were found.

Clinical Course and Management of Patients with Emergency Surgery Treated with Direct Oral Anticoagulants or Vitamin K Antagonists-Results of the German Prospective RADOA-Registry.

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) (p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients (p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site (p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials.

Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174days to 3.38years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.

Effectiveness and safety of oral anticoagulant therapy in a real-world cohort with atrial fibrillation: The SIESTA-A study protocol.

Oral anticoagulants (OACs) are first-line drugs for stroke prevention in patients with atrial fibrillation (AF). The introduction of new lines of therapy with direct oral anticoagulants (DOACs) has led to a decreased use of vitamin K antagonists (VKAs). Comparative analyses of DOACs in clinical trials are scarce and the comparator has mostly been warfarin. Their impact on health outcomes in observational studies has not always been consistent. The aim of this study is to evaluate the effectiveness and safety of DOACs and VKAs in patients with AF using Real-World Data (RWD). Population-based retrospective cohort study using RWD from actual practice. Period: January 2012-December 2020. Inclusion criteria: patients with AF who had not taken OACs in the previous 12 months. Exclusion criteria: <40 years, with severe mitral stenosis, or valvular heart disease or aortic and/or mitral valve procedures. Data source: The Andalusian Population Health Database, Spain. Outcome measures: a) Effectiveness: ischaemic stroke, transient ischaemic attack, systemic and pulmonary embolism, and death; b) Safety: gastrointestinal and intracranial haemorrhaging; Independent variables: age, sex, comorbidities, medication and health resource use, CHA2DS2-VASC, HAS-BLED, and analytical tests. Statistical analysis: crude incidence analysis, survival models, Kaplan-Meier, Cox regression analysis adjusted for possible confounding and paired analysis by propensity score matching.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic haemodialysis: a systematic review and meta-analysis of randomised controlled trials

Abstract Background Patients with atrial fibrillation (AF) and end-stage renal disease on chronic haemodialysis (HD) are at risk for thromboembolic and bleeding events. The safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population remains unclear. Purpose This systematic review and meta-analysis aimed to compare DOACs with VKAs in patients with AF on chronic HD with regards to cardiovascular mortality, all-cause mortality, ischaemic or uncertain type of stroke, and major or life-threatening bleeding. Methods We systematically searched PubMed, EMBASE, and Cochrane Library for randomised controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic HD from inception to February 2023 in accordance with PRISMA guidelines. Statistical analyses were performed using Review Manager 5.4.1. Heterogeneity was evaluated using I2 statistics. We performed the data extraction following the intention-to-treat principle. Results We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomised to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.35; 95% CI 0.71–2.60; p=0.36; I2=0%; Fig. 1A), all-cause mortality (RR 0.99; 95% CI 0.76–1.30; p=0.96; I2=11%; Fig. 1B), ischaemic or uncertain type of stroke (RR 0.52; 95% CI 0.18–1.48; p=0.22; I2=0%; Fig. 2A), or major or life-threatening bleeding (RR 0.69; 95% CI 0.42–1.14; p=0.15; I2=20%; Fig. 2B), with an overall low between-study heterogeneity. Conclusion In this meta-analysis, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischaemic or uncertain type of stroke, nor major or life-threatening bleeding in patients with AF on chronic HD.Figure 1Figure 2

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation: a systematic review and meta-analysis

Abstract Background The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) have not been well established yet. Purpose This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. Methods PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. Results Five studies involving 8103 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a significant lower risk of all-cause death [RR (95%CI): 0.44 (0.35-0.55)]. Meanwhile, DOAC therapy group was similar to VKA therapy in reducing ischemic stroke [RR (95%CI): 0.65 (0.33-1.28)] and thromboembolic events [RR (95%CI): 0.95 (0.74-1.22)]. The incidence of major bleeding [RR (95%CI): 0.69 (0.44-1.07)] were comparable between the two groups. Conclusion In patients with HCM and AF, DOAC therapy were superior or non-inferior to VKA therapy in reducing the risk of all-cause death and thromboembolic events, without increasing bleeding risk. Further RCTs are needed to provide more evidence for DOAC therapy in this population.Efficacy and safety endpoints in DOAC th

Clinical outcomes in patients receiving oral anticoagulation stratified by the presence of dose reduction criteria and older age: a subanalysis of ENVISAGE-TAVI AF

Abstract Background/Introduction In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban (EDX) was noninferior to vitamin K antagonists (VKAs) for preventing most adverse clinical events but was associated with increased major bleeding (MB). Presence of EDX dose reduction criteria applied in the trial (DRC; body weight ≤60 kg, CrCL 15–50 mL/min, concomitant use of selected P-glycoprotein-inhibitors) indicates a more vulnerable patient phenotype. Purpose Compare clinical outcomes after TAVI for AF patients with and without DRC stratified by anticoagulation strategy and age. Methods ENVISAGE-TAVI AF (NCT02943785) was a multicentre, open-label, randomised, controlled trial comparing EDX vs VKA in patients with AF as the indication for oral anticoagulation (OAC) after successful TAVI. In this analysis, outcomes—which included net adverse clinical events (NACE; composite all-cause death, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or MB), intracranial haemorrhage, ischaemic stroke, all-cause death, cardiovascular (CV) death, non-CV death, MB bleeding, fatal MB bleeding, and major gastrointestinal bleeding (MGIB) —were compared in patients with vs without DRC, further stratified by OAC use, and age (&amp;lt; or ≥80 years [y]). Results Patients meeting DRC (n=637) were older, more often female, and had lower baseline CrCL than those without (n=740). In addition, these patients had significantly higher rates of NACE (P=0.0375) and all-cause death (P=0.0136). There were no differences in MB or MGIB rates between patients with vs without DRC. EDX resulted in more MB (hazard ratio [95% CI], 1.6 [1.1–2.5] and MGIB (2.6 [1.2–5.8]) than VKA only in patients without DRC. In patients aged &amp;lt;80 y meeting DRC, rates of all-cause death (P=0.0366) and CV death (P=0.0042) were significantly higher than those without DRC. Among patients aged &amp;lt;80 y, there were no differences in rates of clinical outcomes between EDX and VKA regardless of the presence or absence of DRC; Figure 1). In patients aged ≥80 y, there were no differences in rates of all-cause death, MB, or MGIB in those with or without DRC; Figure 2). Additionally in this age group, there was no difference in MB between patients on EDX and VKA both with and without DRC. However, there was more MGIB with EDX when there were no DRC. In patients aged ≥80 y with DRC, all-cause death was lower with EDX. Conclusions In this subanalysis of ENVISAGE-TAVI AF, the presence of DRC indicates a more vulnerable patient phenotype at higher risk for all-cause death after TAVI and in whom a lower EDX dose may have substantial benefits in terms of outcomes, including bleeding events, particularly in patients ≥80 y.Figure 1Figure 2

Baseline characteristics and outcomes of extended oral anticoagulant treatment in patients with venous thrombosis: a retrospective cohort study in France

Abstract Background Guidelines recommend anticoagulant (AC) extended treatment for patients with unprovoked VTE or VTE provoked by permanent risk factors (ESC 2019, CHEST 2021). A recent observational study has shown that apixaban extended treatment (&amp;gt;6 months) vs no extended treatment in patients with venous thromboembolism (VTE), regardless of risk factors, is associated with decreased risk of recurrent VTE (rVTE), with no increase in major bleeding. A better safety profile for patients receiving apixaban vs those receiving vitamin K antagonists (VKAs) was also observed. Purpose To describe characteristics of patients with VTE receiving AC extended treatment (&amp;gt;6months) vs those receiving acute treatment only (&amp;lt;6 months). Outcomes among patients receiving extended treatment with apixaban and VKAs were also reported. Methods The presence of risk factors were assessed in a nationwide retrospective cohort study of AC treatment-naïve adult patients (identified via the French national health data system: SNDS) with VTE, who were prescribed VKAs or apixaban from 2013 to 2018. Descriptive statistics for patients receiving AC extended treatment vs those receiving only acute treatment are presented. Risk of bleeding (based on principal diagnoses of hospital stays), rVTE (based on principal diagnosis of hospital stays and specified procedures), and all-cause mortality were assessed 18 months following the initiation of extended treatment using inverse probability treatment weighted (IPTW) analysis to balance baseline socio-demographic and clinical characteristics. Results 21,215 VTE patients who initiated AC treatment were included: 10,775 VKAs (41.5% acute vs 58.5% extended treatment) and 10,440 apixaban (44.5% acute vs and 55.5% extended treatment). A higher proportion of apixaban and VKA patients with permanent risk factors (apixaban: 57.7%; VKAs: 57.7%) or unprovoked VTE (apixaban: 56.8%; VKAs: 59.7%) received extended treatment vs acute treatment only. Table 1 shows the adverse clinical outcomes assessed during extended treatment in IPTW balanced cohorts. Compared to patients treated with VKAs (n=6151), patients treated with apixaban (n=5682) had lower rates of rVTE (1.89 vs 2.84 per 100 person-years), bleeding (1.11 vs 1.69 per 100 person-years) and all-cause mortality (2.70 vs 6.74 per 100 person-years). Conclusions A slightly higher proportions of patients with permanent VTE risk factors and unprovoked VTE received extended treatment compared to acute treatment. Consistent with guidelines, there persists a need to increase these rates when clinically indicated to improve patient outcomes. Clinical event rates were numerically lower for apixaban compared to VKAs, which suggests clinical benefit for apixaban. However, more robust confirmatory analyses are required.