Versus Vitamin K Antagonists Research Articles

Factor Xa inhibitors versus vitamin K antagonist in morbidly obese patients with venous thromboembolism: a systematic review and meta-analysis

IntroductionGuidelines have endorsed non-vitamin K antagonist oral anticoagulants (NOACs), consisting of factor Xa inhibitors (xabans) and direct thrombin inhibitors, as the first line of treatment in venous thromboembolism (VTE) and atrial fibrillation. However, morbidly obese patients were under-represented in landmark trials of NOACs. Therefore, this study aimed to systematically review and perform a meta-analysis of studies on xabans versus vitamin K antagonist (VKA) in this high-risk population with VTE.MethodsPubMed, Embase, Medline, Cochrane library, and Google Scholar databases were searched to identify studies that compared xabans and VKA in treating morbidly obese patients with VTE. Morbid obesity was defined as body weight ≥ 120 kg or BMI ≥ 40 kg/m2. Outcomes of interest included recurrent VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB).ResultsEight studies comprising 30,895 patients were included. A total of 12,755 patients received xabans while 18,140 received VKAs. No significant difference in the odds of recurrent VTE (OR 0.75, 95% CI 0.55–1.01) and CRNMB (OR 0.69, 95% CI 0.44–1.09) was observed between the xabans group and the VKA group. However, the xabans group was associated with lower odds of major bleeding (OR 0.70, 95% CI 0.59–0.83).ConclusionXabans have lower odds of major bleeding but similar odds of recurrent VTE when compared with VKAs in treating VTE in morbidly obese patients. Large registry analyses or future randomized controlled trials will be helpful in confirming these findings.

The efficacy and safety of direct oral anticoagulants versus vitamin K antagonists in patients with left-sided bioprosthetic heart valves and atrial fibrillation: a systematic review and meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for the treatment of patients with left-sided bioprosthetic heart valves (BHV) and atrial fibrillation (AF) remain controversial. This study aims to perform a meta-analysis to evaluate the efficacy and safety of DOACs versus VKAs in this region. We retrieved all relevant randomized controlled studies and observational cohort studies, which critically assessed the efficacy and safety of DOACs versus VKAs among patients with left-sided BHV and AF in databases of PubMed, Cochrane, ISI Web of Sciences, and Embase. The efficacy outcomes of this meta-analysis were stroke events and all-cause death when the safety outcomes included major and any bleeding. The analysis integrated 13 studies while enrolling 27,793 patients with AF and left-sided BHV. DOACs reduced the rate of stroke by 33% compared with VKAs (risk ratio [RR] 0.67; 95% CI 0.50-0.91), with no increased incidence of all-cause death (RR 0.96; 95% CI 0.82-1.12). For safety outcomes, major bleeding was reduced by 28% using DOACs rather than VKAs (RR 0.72; 95% CI 0.52-0.99), while there was no difference in the events of any bleeding (RR 0.84; 95% CI 0.68-1.03). In addition, in patients younger than 75years old, the stroke rate was reduced by 45% in the population using DOACs (RR 0.55; 95% CI 0.37-0.84). Our meta-analysis demonstrated that in patients with AF and BHV, compared with VKAs, using DOACs was associated with reduced stroke and major bleeding events without an increase of all-cause mortality and any bleeding. In the population younger than 75years old, DOAC might be more effective in preventing cardiogenic stroke.

EP News: Allied Professionals.

In this randomized controlled trial, Connolly et al (N Engl J Med 2022;387:978, PMID 36036525) sought to assess the safety and efficacy of rivaroxaban vs vitamin K antagonists (VKAs) in patients with rheumatic heart disease (RHD) and atrial fibrillation (AF). Patients with RHD were routinely excluded from the pivotal trials comparing rivaroxaban and other non-VKA oral anticoagulants (NOACs) with the VKA warfarin. The INVICTUS trial (Investigation of Rheumatic AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies) was conducted in 138 sites in 34 countries in Africa, Latin America, and Asia.

Direct Oral Anticoagulants (DOACs) are Non-Inferior to Vitamin K Antagonists for Patients Undergoing Transcatheter Aortic Valve Replacement with Indications of Anticoagulation.

The best anticoagulation choice for patients undergoing transcatheter aortic valve replacement (TAVR) with indications of oral anticoagulation (OAC) remains uncertain. We carried out a comprehensive analysis adopting updated evidence that investigated the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in this population. A systematic search has been conducted through PubMed, Embase, and Cochrane Library to collect randomized controlled trials (RCTs) and real-world studies comparing the therapy outcomes of DOACs with VKAs in patients undergoing TAVR with indications of OAC up to Dec 2021. Included studies reported all-cause mortality, bleeding, stroke, or composite endpoint. A random-effects model was used and followed a sensitivity analysis based on the heterogeneity. In addition, five scenario analyses were performed to robust our findings. Our analysis included 11 articles enrolling a total of 8934 patients undergone TAVR with indications of OAC (DOACs group = 3890, VKAs group = 5044). Pooled analysis revealed no significant different risk of all-cause mortality (aHR: 0.95, 95% CI: 0.65-1.39, : 90.6%), stroke (aHR: 0.86, 95% CI: 0.55-1.35, : 44.3%), bleeding (aHR: 0.83, 95% CI: 0.61-1.13, : 76.3%), and composite endpoint (aHR: 1.05, 95% CI: 0.88-1.24, : 11.7%) in the DOACs and VKAs groups. Various forms of death, stroke and bleeding, including cardiovascular death (aHR: 0.92, 95% CI: 0.64-1.33, : 34.1%), hemorrhagic stroke (aHR: 0.63, 95% CI: 0.23-1.75, : 22.7%), ischemic stroke (aHR: 0.79, 95% CI: 0.56-1.15, : 0.0%), transient ischemic attack (aHR: 0.75, 95% CI: 0.40-1.41, : 0.0%), major or life-threatening bleeding (aHR: 0.96, 95% CI: 0.74-1.24, : 27.9%), and minor bleeding (aHR: 0.90, 95% CI: 0.52-1.57, : 54.3%), also showed similar rates among DOACs and VKAs groups. The results based on five scenarios confirmed the said findings. Compared with VKAs, the efficacy and safety of DOACs were comparable for treating TAVR patients combined with anticoagulation indications. Further large-scale RCTs investigating more detailed scenarios are still needed to confirm the optimal anticoagulation strategy.

Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model. From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, : 58.83%). Our aforementioned subgroup analyses revealed similar results. All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

Direct oral anticoagulants compared to vitamin K antagonists for the treatment of left ventricular thrombi

Abstract Background Left ventricular thrombus (LVT) complicates around one in six cases of acute and chronic left ventricular systolic dysfunction and is associated with an increased risk of stroke, major systemic embolism and death, believed to be ameliorated by anticoagulation. Off-label use of direct oral anticoagulants (DOACs) for LVT has steadily increased, largely based on favourable outcomes in atrial fibrillation and venous thromboembolism, but the safety and efficacy of DOACs versus vitamin K antagonists (VKA) for LVT remains uncertain. Purpose The main aim of our study was to compare treatment of LVT with VKA to DOAC, focusing on all-cause mortality, stroke, major systemic emboli and major bleeding. Methods We conducted a retrospective observational longitudinal study of patients presenting to two large quaternary centres between 2011 and 2021 with a diagnosis of LVT. Patients were eligible if they had a documented LVT and received anticoagulation with either VKA or DOAC. Baseline data, thrombus characteristics, treatment type and duration, follow up imaging and clinical events were recorded using electronic health care records. Outcome measures included thrombus resolution, stroke and systemic embolism (SSE), major bleeding and mortality. Results A total of 955 patients were identified, of whom 901 received treatment with either a VKA (567 pts, 62.9%) or a DOAC (334 pts, 37.1%) and were included in the analysis. Underlying aetiologies included acute myocardial infarction (AMI) (38.3%), chronic ischaemic cardiomyopathy (38.0%) and non-ischaemic cardiomyopathy (23.7%). Rivaroxaban (43.4%) was the most frequently prescribed DOAC followed by apixaban (35.9%), and the remaining on edoxaban (20.7%). AMI related LVT was more commonly treated with DOAC (53.0%) and chronic ischaemic cardiomyopathy with VKA (72.9%). There was a lower baseline LVEF in the VKA cohort (29.5±13.2 vs 33.1±14.2, p<0.0001). Other demographic features were comparable. Median follow up was 2.5 years (IQR: 1–3.5). There were no differences in follow up duration between the two treatments (p=0.17). Greater rates of thrombus resolution were seen in the DOAC group compared to VKA (1 year: 78.4% vs 51.4%, p<0.0001), with higher rates of persistent thrombus over the follow-up period seen in the VKA group (25.1% vs 12.9%, p<0.0001). Rates of stroke and systemic embolization were similar between the groups (VKA 9.3% vs 9.6% DOAC, p=0.93). Higher rates of bleeding (BARC >3, 8.1% VKA, 3.6% DOAC, p=0.031) (Figure 1A) and mortality (VKA 18.5%, DOAC 10.2%, p=0.001) (Figure 1B) were seen in the VKA group over the follow-up period. Conclusions In a large multi-centre registry of LVT of mixed aetiology, anticoagulation with DOAC was associated with earlier and greater rates of thrombus resolution and consequential reduced adverse events (major bleeding and mortality) during follow up. A funding application to support a multi-centre randomised control trial is underway. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by the British Heart Foundation (Fellowship FS/CRTF/21/24190 to HM) and the National Institute for Health Research (Biomedical Research Centre Award to Guy's and St Thomas' NHS FT and King's College London).

To compare efficacy and safety of direct oral anticoagulants in patients with concurrent atrial fibrillation and bioprosthetic heart valve repair or replacement: a systematic review and meta-analysis

Abstract Background Use of direct oral anticoagulants (DOACs) is contraindicated in patients with mechanical valves. However data on their use in patients with atrial fibrillation (AF) and bioprosthetic valves (BV) is still limited. Purpose To assess the safety and efficacy of DOACs versus Vitamin K antagonist (VKA) in patients with AF after BV repair or replacement. Methods We performed a comprehensive review of electronic databases (PubMed, Embase, Scopus, Cochrane) using MeSH terms and keywords for DOACs, AF and BVs from inception through December 2021. Randomized clinical trials (RCT) or observational studies that reported clinical outcomes comparing DOACs versus VKA in patients with AF and BVs were eligible for inclusion. Ten articles were reviewed for full text. Primary outcome was a composite of all cause stroke or systemic embolic event. Secondary outcomes included major bleeding and all-cause mortality. Subgroup analysis stratified by study design was performed. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using Mantel-Haenszel method with DerSimonian-Laird estimator for tau2 for random effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis was performed using RevMan 5.4.1 software. Results Ten studies (5 RCTs, 5 observational studies) with a total of 5,333 patients (DOACs n=2434; VKA n=2899) were included. Aortic, mitral and mixed BV repair or replacement were 74.2%, 25.6% and 0.02% respectively. The mean age was 72.6±11.9 years. The mean follow-up was 15.7±12.9 months. Type of DOACs included apixaban (n=553, 22.7%), rivaroxaban (n=893, 36.7%), dabigatran (n=151, 6.2%) and edoxaban (n=837, 34.4%). There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.79; CI: 0.56–1.11; p>0.05; I2=12%) or secondary outcomes of major bleeding (RR: 0.84; CI: 0.64–1.11; p>0.05; I2=45%), and all-cause mortality (RR: 0.84; CI: 0.64–1.11; p>0.05; I2=29%) between DOACs compared with VKA. Conclusion In patients with AF and BV, DOACs are non-inferior to VKA for risk of stroke or systemic embolism, major bleeding, and all-cause mortality. Thus, DOACs can serve as a viable alternative to VKAs which have a narrow therapeutic index, multiple drug interactions, and require frequent monitoring. Funding Acknowledgement Type of funding sources: None.

Comparing direct oral anticoagulants versus vitamin K antagonist in patients with atrial fibrillation after transcatheter aortic valve replacement: an updated meta-analysis

Abstract Background Oral anticoagulation therapy is indicated for patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant or new onset atrial fibrillation (AF). However the data on optimal anticoagulation regimen in this population remains unclear. Purpose To compare efficacy and safety outcomes of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKA) in patients with AF post TAVR. Methods We searched electronic databases (PubMed, Embase, Scopus, Cochrane) from inception to February28th, 2022 using MeSH terms and keywords for DOACs, AF or TAVR. Primary outcome of interest was all-cause stroke or systemic embolic event. Secondary safety outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis were performed using RevMan 5.4.1 software. Results We identified five eligible studies (1RCT, 4 observational) including 3694 patients (DOAC n=1581, VKA n=2113). The mean age was 81.4±0.9 years. The mean follow-up was 12.4±14.3 months. Type of DOACs included apixaban (n=394, 24.9%), rivaroxaban (n=354, 22.4%), dabigatran (n=119, 7.5%) and edoxaban (n=714, 45.2%).There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.93; CI: 0.65–1.33; p>0.05; I2=5%), or in secondary outcomes of major bleeding (RR: 1.02; CI: 0.78–1.34; p>0.05; I2=44%) and all-cause mortality (RR: 0.87; CI: 0.59–1.27; p>0.05; I2=56%) between DOACs and VKA groups. Conclusion This meta-analysis shows anticoagulation therapy with DOACs has similar safety and efficacy outcomes compared to VKA in patients with AF undergoing TAVR. Funding Acknowledgement Type of funding sources: None.

Direct oral anticoagulants for the treatment of left ventricular thrombosis: an updated systematic review and meta-analysis.

This meta-analysis aims to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in the setting of left ventricular thrombosis (LVT). We systematically searched MEDLINE, Cochrane Library, Biomed Central and Web of Science for trials comparing DOACs versus VKAs in the setting of LVT and reporting outcome data on thrombosis resolution, stroke and bleeding. Fourteen studies were finally selected. The Mantel-Haenszel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of LVT resolution. The secondary outcomes were the occurrence of stroke or bleeding during treatment. One thousand three hundred and thirty-two patients were included in the analysis for the primary outcome. Of these, 424 were treated with DOACs and 908 with VKAs. The pooled odds ratio (OR) for the primary outcome was 1.00 [95% confidence interval (95% CI) 0.77-1.31, I2 0.0%], reflecting equal effect in terms of thrombus resolution. Overall, 2290 patients, 608 on DOACs and 1682 on VKAs were included in the analysis of stroke occurrence, showing reduced risk of events in patients treated with DOACs (pooled OR 0.58, 95% CI 0.36-0.93; I2 0.0%) as well as for bleeding occurrence (number of patients included 2139; pooled OR 0.64, 95% CI 0.44-0.94; I2 0.0%). Compared with VKAs, we found DOACs to have similar efficacy on thrombus resolution and favorable effects on stroke reduction and bleedings. DOACs should be considered as an alternative treatment for LVT. Large prospective randomized clinical trials are needed to confirm this exploratory finding.

Early Anticoagulation in Patients with Acute Ischemic Stroke Due to Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Introduction: There is uncertainty regarding the optimal timing for initiation of oral anticoagulation in patients with acute ischemic stroke (AIS) due to atrial fibrillation (AF). Methods: We performed a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) and prospective observational studies to assess the efficacy and safety of early anticoagulation in AF-related AIS (within 1 week versus 2 weeks). A second comparison was performed assessing the efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin-K antagonists (VKAs) in the two early time windows. The outcomes of interest were IS recurrence, all-cause mortality, symptomatic intracerebral haemorrhage (sICH) and any ICH. Results: Eight eligible studies (6 observational, 2 RCTs) were identified, including 5616 patients with AF-related AIS who received early anticoagulation. Patients that received anticoagulants within the first week after index stroke had similar rate of recurrent IS, sICH and all-cause mortality compared to patients that received anticoagulation within two weeks (test for subgroup differences p = 0.1677; p = 0.8941; and p = 0.7786, respectively). When DOACs were compared to VKAs, there was a significant decline of IS recurrence in DOAC-treated patients compared to VKAs (RR: 0.65; 95%CI: 0.52–0.82), which was evident in both time windows of treatment initiation. DOACs were also associated with lower likelihood of sICH and all-cause mortality. Conclusions: Early initiation of anticoagulation within the first week may have a similar efficacy and safety profile compared to later anticoagulation (within two weeks), while DOACs seem more effective in terms of IS recurrence and survival compared to VKAs.

CE-539-03 LARGE OBSERVATIONAL STUDY EVALUATING SAFETY AND EFFICACY OF DIRECT ORAL ANTICOAGULANTS IN EXTREME OBESITY

Obesity is an independent risk factor for atrial fibrillation (AF) influencing the pharmacokinetics and pharmacodynamics of drug therapy and direct oral anticoagulants (DOACs). There is limited data in the randomized clinical trials for patients with extreme obesity (BMI ≥ 40.0 kg/m2 or weight > 120 Kg). To evaluate the effectiveness and safety of DOACs versus vitamin K antagonists (VKA) for the treatment of nonvalvular AF (NVAF) in extreme obese patients. Using retrospective cohort study design, adult extreme obese patients with NVAF using DOACs or VKA during 2014 - 2020 with BMI ≥ 40.0 or weight > 120 Kg were selected from a large south-east hospital system. Patients were categorized into four groups based on BMI and weight (weight > 120 Kg and BMI ≤ 40; BMI 41-44; BMI 45-49; BMI ≥ 50). Primary efficacy outcome is stroke or systemic embolism (SE) and primary safety outcome is major bleeding. A total of 6,930 patients with a mean age of 64.1 years and a mean follow-up of 3.8 ±2.3 years were included. Extreme obese groups I through 4 included 2216 (32%), 2240 (32.3%), 1277 (18.4%), and 1197 (17.3%) with DAOCs use ranging from 60% to 63%. In Cox regression for the entire cohort, DOACs were associated with a significantly lower risk of stroke or SE (hazard ratio [HR]: 0.52; 95% confidence interval [CI]: 0.42, 0.65) and major bleeding (HR: 0.55; 95% CI: 0.59, 0.90) compared to VKA. Results remained similar across all groups except non-significant results for groups 3 and 4 for major bleeding. DOAC utilization in patients with extreme obesity was far greater than use of VKA despite not having significant clinical trial evidence of safety and efficacy in this unique population. Our observational retrospective study revealed significantly better prevention of stroke or SE without increased major bleeding in patients who are on DOACs versus VKA.

Dabigatran versus vitamin K antagonists for atrial fibrillation in clinical practice: final outcomes from Phase III of the GLORIA-AF registry

BackgroundProspectively collected, routine clinical practice-based data on antithrombotic therapy in non-valvular atrial fibrillation (AF) patients are important for assessing real-world comparative outcomes. The objective was to compare the safety and effectiveness of dabigatran versus vitamin K antagonists (VKAs) in patients with newly diagnosed AF.Methods and resultsGLORIA-AF is a large, prospective, global registry program. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc scores ≥ 1 were included and followed for 3 years. To control for differences in patient characteristics, the comparative analysis for dabigatran versus VKA was performed on a propensity score (PS)-matched patient set. Missing data were multiply imputed. Proportional-hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Between 2014 and 2016, 21,300 eligible patients were included worldwide: 3839 patients were prescribed dabigatran and 4836 VKA with a median age of 71.0 and 72.0 years, respectively; > 85% in each group had a CHA2DS2-VASc-score ≥ 2. The PS-matched comparative analysis for dabigatran and VKA included on average 3326 pairs of matched initiators. For dabigatran versus VKAs, adjusted HRs (95% confidence intervals) were: stroke 0.89 (0.59–1.34), major bleeding 0.61 (0.42–0.88), all-cause death 0.78 (0.63–0.97), and myocardial infarction 0.89 (0.53–1.48). Further analyses stratified by PS and region provided similar results.ConclusionsDabigatran was associated with a 39% reduced risk of major bleeding and 22% reduced risk for all-cause death compared with VKA. Stroke and myocardial infarction risks were similar, confirming a more favorable benefit-risk profile for dabigatran compared with VKA in clinical practice.Clinical trial registrationhttps://www.clinicaltrials.gov. NCT01468701, NCT01671007.Graphical abstract

Non-vitamin K oral anticoagulants versus vitamin K antagonists in post transcatheter aortic valve replacement patients with clinical indication for oral anticoagulation: A meta-analysis.

BackgroundCurrent guidelines recommend oral anticoagulation (OAC) following transcatheter aortic valve replacement (TAVR) in patients with clinical indication, but the optimal antithrombotic regimen remains uncertain. We aimed to compare the efficacy and safety of non‐vitamin K oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in patients undergoing TAVR with concomitant indication of OAC.HypothesisComparing with VKAs therapy, NOACs are similar in reducing the all‐cause mortality and major bleeding in post‐TAVR patients requiring OAC medication.MethodsWe searched the databases of PubMed, Embase, and Cochrane library databases to identify studies that investigated NOACs versus VKAs after TAVR in patients with another indication of OAC, which were published before 28th September 28, 2021. The effectiveness of outcomes was all‐cause mortality and stroke or systemic embolism, while the main safety outcome was major and/or life‐threatening bleeding. The hazard ratio (HR) with 95% confidence interval (CI) was used as a measure of treatment effect.ResultsOur search identified eight studies. We included 4947 post‐TAVR patients with another indication of OAC allocated to the NOAC (n = 2146) or VKA groups (n = 2801). There were no significant differences in the all‐cause mortality (HR: 0.91, 95% CI: 0.77–1.08, p = .29, I 2 = 47%), stroke or systemic embolism (HR: 0.96, 95% CI: 0.68–1.37, p = .84, I 2 = 0%), and major and/or life‐threatening bleeding (HR: 1.09, 95% CI: 0.89–1.32, p = .40, I 2 = 30%) in both groups.ConclusionAmong post‐TAVR patients who required OAC therapy, NOACs therapy compared to VKAs is similar in reducing the all‐cause mortality, stroke or systemic embolism, and major and/or life‐threatening bleeding events.

Abstract TMP74: Direct Oral Anticoagulants Vs. Vitamin K Antagonists In Patients With Cerebral Venous Thrombosis: A Systematic Review And Meta-analysis

Introduction: Direct oral anticoagulants (DOACs) have emerged as a potential anticoagulant therapy for patients with cerebral venous thrombosis (CVT). We conducted a systematic review and meta-analysis comparing DOACs versus vitamin K antagonists (VKAs) for treatment of CVT. Methods: We registered the review in PROSPERO (registration number CRD42021228800). We searched Medline, Embase, CINAHL, and the Web of Science Core Collection from January 1, 2007, to May 26, 2021. We included randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) evaluating key outcomes for efficacy (recurrent venous thromboembolism [VTE] and complete recanalization) and safety (major hemorrhage). We assessed risk of bias using the Cochrane Risk of Bias Tool 2.0 (for RCTs) and the ROBINS-I tool (for NRCSs). Where studies were sufficiently similar, we performed meta-analyses using random-effects models. This review was funded by Brown Neurology. Results: Of 8213 identified records,10 studies (1 RCT and 9 NRCSs) with a total of 662 patients (33% DOAC and 67% VKAs) met the inclusion criteria. We will present our risk of bias assessment at the conference. DOACs and VKAs had comparable efficacy: recurrent VTE (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.44-2.23; I 2 =0%; 10 studies) and complete recanalization (RR 1.00, 95% CI 0.77-1.28; I 2 =0%; 6 studies). DOAC and VKA also had comparable safety: major hemorrhage (RR 0.89, 95% CI 0.37-2.14; I 2 =0%; 9 studies). Conclusions: Studies comparing DOACs with VKAs in patients with CVT consist mostly of small, non-randomized, poorly controlled studies. While the two treatments appear comparable for major efficacy and safety outcomes, large, rigorously conducted studies, preferably randomized, are needed to overcome these limitations and permit development of clinical practice guidelines for the use of DOACs in patients with CVT.

Impact of prior oral anticoagulant use and outcomes on patients from secondary analysis in the AUGUSTUS trial

ObjectiveManaging antithrombotic therapy in patients with atrial fibrillation (AF) and an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is challenging and can be affected by prior oral anticoagulant...

Severity of gastrointestinal bleeding is similar between patients receiving direct oral anticoagulants or vitamin K antagonists.

Gastrointestinal bleeding (GIB) is a common adverse event related to anticoagulation therapy. However, evidence comparing the severity, etiology and outcome of GIB in patients taking direct oral anticoagulants (DOAC) vs. vitamin K antagonists (VKA) is scarce. To evaluate the severity, etiology and outcomes of GIB in patients under DOACs compared to VKA. Patients under oral anticoagulant therapy admitted to the emergency department with acute GIB were prospectively recruited from July 2016 to January 2018 at a tertiary referral hospital. Demographic and clinical outcome were obtained from medical records. Severity of the GIB event was classified as mild, major or severe according to clinical presentation and the type of support needed. Etiology and location of bleeding, number of packed red blood cells transfused (PRBC) and length of hospital stay were recorded until discharge or in-hospital death. A total of 208 patients with acute GIB under oral anticoagulant treatment were recruited: 119 patients were on VKA and 89 patients on DOAC with similar characteristics. Thirty-one patients had severe GIB; 134 major and 43 mild, with no differences in severity, number of PRBC and length of hospital stay between the groups. Peptic disease was the most frequent etiology of GIB in patients on VKA (20.2 % vs. 13.6%, p=0.20). Diverticular bleeding was the most frequent adverse event in patients on DOAC (14.3% vs. 24.8%, p= 0.056). Severity and clinical outcomes of GIB are similar between patients on DOAC and patients on VKA, regardless of etiology of GIB.

Direct oral anticoagulants versus vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis.

Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs versus vitamin K antagonists (VKAs) in LVT treatment. Systematic search of studies evaluating DOACs versus VKAs use in patients with LVT was performed on May 11th, 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, hemorrhagic stroke, and all cause death. Twenty studies were included in the meta-analysis: 1,391 patients were treated with DOACs and 1,534 with VKAs. A significant reduction in the risk of ischemic stroke (OR 0.67, 95% CI, 0.45-0.98, P=0.048, number needed to treat to benefit [NNTB] 22 [95% CI 15-43]) and any bleeding (OR 0.64, 95% CI 0.46-0.89, P=0.009, NNTB 26 [95% CI 16-80]) was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. Compared to VKAs, DOACs are associated with a reduced risk of ischemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

21 Direct oral anticoagulants vs. vitamin K antagonists in the treatment of left ventricular thrombosis: a systematic review and meta-analysis

Abstract Aims Evidence about the use of direct oral anticoagulants (DOACs) in patients with left ventricular thrombosis (LVT) are emerging. The aim of our study was to provide a comprehensive synthesis of the available evidence concerning the clinical effects of DOACs vs. vitamin K antagonists (VKAs) in LVT treatment. Methods Systematic search of studies evaluating DOACs vs. VKAs use in patients with LVT was performed on 11 May 2021. Data were pooled by meta-analysis using a random-effects model. Odds ratios (OR) with relative 95% confidence intervals (CI) were used as measures of effect estimates. The primary efficacy and safety endpoint were ischaemic stroke and any bleeding, respectively. Secondary endpoints were LVT resolution, systemic embolism, major bleeding, haemorrhagic stroke, and all cause death. Results Twenty studies were included in the meta-analysis: 1391 patients were treated with DOACs and 1534 with VKAs. A significant reduction in the risk of ischaemic stroke [OR 0.67, 95% CI 0.45–0.98, P = 0.048, number needed to treat to benefit (NNTB) 22 (95% CI 15–43)] and any bleeding [OR 0.64, 95% CI 0.46–0.89, P = 0.009, NNTB 26 (95% CI 16–80)] was observed with DOACs compared to VKAs. No statistically significant difference was observed among the two treatment arms for the secondary endpoints. Conclusion Compared to VKAs, DOACs are associated with a reduced risk of ischaemic stroke and bleeding. In light of these findings, and the practical advantages of DOACs, additional large scale randomized controlled trials are needed to confirm the benefits of DOACs in patients with LVT.

Patient perception and treatment convenience of dabigatran versus vitamin K antagonist when used for stroke prophylaxis in atrial fibrillation: Real-world Evaluation of Long-term Anticoagulant Treatment Experience (RE-LATE) study

PurposeDabigatran is a direct thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Real-world data about patient preference, satisfaction and convenience in patients in Asia are...

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation.

ObjectiveTo investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin K antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years.MethodsIndividual patient data analysis from seven prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all‐cause death. We used simple, adjusted, and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk.ResultsIn total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient‐years follow‐up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y = 0.65, 95%‐CI [0.52, 0.81]) and < 85 years (HR<85y = 0.79, 95%‐CI [0.66, 0.95]) in simple (pinteraction = 0.129), adjusted (pinteraction = 0.094) or weighted (pinteraction = 0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and < 85 years (+1.90 to +3.36 events/100 patient‐years for ICH‐weights 1.5 to 3.1).InterpretationThe favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old. ANN NEUROL 2022;91:78–88