Effectiveness Of Direct Oral Anticoagulants Research Articles

DOACs or warfarin use in morbidly obese patients (BMI > 40 kg/m2) on anticoagulant therapy? : a systematic review and meta-analysis

Abstract Introduction Current guidelines and consensus statements have advised against the use of direct oral anticoagulants (DOACs) for morbidly obese patients (BMI > 40 kg/m2), indicating warfarin as the first-line treatment. Purpose Our aim was to systematically review and examine the effectiveness and safety of DOACs compared to warfarin in patients with BMI > 40 kg/m2 and atrial fibrillation (AF) or venous thromboembolism (VTE). Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies comparing the effectiveness and safety of DOACs and Warfarin in extremely obese patients. The primary outcome was the incidence of the composite endpoint (stroke, systemic embolism, myocardial infarction, or all-cause mortality), ii) stroke/systematic embolism (SE) and, iii) VTE. Secondary endpoints referred to major and minor bleeding events. Results This meta-analysis comprised 16 studies and 114,999 morbidly obese patients with AF or VTE on oral anticoagulation therapy (48,937 on DOACs vs. 65,080 on Warfarin). The DOAC use was significantly associated with lower all-cause mortality and major bleeding rates compared to the warfarin group [risk ratio= 0.66; 95% confidence interval: 0.53, 0.81; p = 0.03; I2 = 60%, RR: 0.78 (95% CI: 0.6-1.01, p <0.01, I2 = 85%)]. Although the rates of composite endpoint, stroke/SE and VTE were lower in the DOAC group, no statistically significant difference was observed [RR: 0.88 (95% CI: 0.7-1.12, p <0.01, I2 = 86%), RR: 0.92; (95% CI: 0.63-1.35, p <0.01, I2 = 86%), RR: 0.72; (95% CI: 0.46-1.15, p <0.01, I2 = 91%)], indicating no-superiority of Warfarin compared to DOAC use. The rates of minor bleeding events, hemorrhagic stroke and ischemic stroke were lower in the DOAC compared to warfarin groups [RR: 0.78 (95% CI: 0.56-1.10, p <0.01, I2 = 80%), RR: 0.56 (95% CI: 0.26-1.21, p <0.01, I2 = 86%), RR: 0.87; (95% CI: 0.6-1.24, p <0.01, I2 = 81%)]. The same trend favoring DOACs over Warfarin in all the assessed endpoints was observed in the subgroup analysis when results adjusted for the anticoagulation indication (AF or VTE). Conclusions Our findings are of paramount importance indicating, firstly, the non-superiority of Warfarin compared to DOAC use, and secondly, a significantly better profile of DOACs in terms of safety and effectiveness in morbidly obese patients with BMI > 40 kg/m2 in all the assessed endpoints. The findings may aid in the endeavor to enhance the upcoming recommendations for the management of this subgroup.

Usefulness of low-dose direct oral anticoagulants for peripheral deep vein thrombosis of the lower extremities in cancer patients with cancer bleeding lesions

Abstract Background Venous thromboembolism (VTE) is a frequent complication in cancer patients. VTE is often detected as asymptomatic peripheral deep vein thrombosis (DVT). Standard doses of anticoagulants are generally considered difficult to administer in cancer patients due to the high risk of bleeding. However, it has been reported that peripheral DVT worsening to proximal DVT in cancer patients due to increased coagulation tendency, and some strategy for peripheral DVT is required. And the adverse bleeding effects of DOACs have been reported to be dose-dependent. Purpose The aim of this study was to determine the optimal treatment strategy of peripheral DVT in patients with bleeding cancer lesions. In order to do this we compared no anticoagulation, low-dose direct oral anticoagulants (DOACs) and standard-dose DOACs in patients with and without bleeding cancer lesions. Methods A total of 224 consecutive patients with peripheral DVT of the lower extremities (excluding pulmonary thromboembolism or proximal DVT) were included from April 2019 to March 2020. Of these, 172 patients could be followed up by repeated ultrasound examinations for up to 2 years. We investigated retrospectively the change in ultrasound findings between first and second examinations (median interval 44 days). 163 patients were studied, excluding 9 patients who used warfarin or heparin. In 119 of these DOACs were applied, and 44 were without anticoagulation. If the treatment procedure had changed between the first and second ultrasound examinations main treatment procedure was selected and categorized. Results All the patients of low-dose and standard-dose DOACs groups had no major bleeding during follow up period. In the group with cancer bleeding lesion (n=45) there were 12 patients (70.1%) worsening DVT in the group without anticoagulation, 1 patient (4.3%) in the low-dose DOACs and 0 (0%) in the standard-dose DOACs group. There was significant worsening of DVT in the no anticoagulant group compared with low-dose DOACs (P<0.0001), but no significant difference between low-dose DOACs and standard-dose DOACs (P=0.63) in the group with bleeding (see Figure 1). In the group without cancer bleeding (n=118), worsening of DVT occurred in 16 patients (59.3%) without anticoagulation, in 6 patients (16.7%) with low-dose DOACs and in 4 patients (7.3%) with standard-dose DOACs. There was significant worsening of DVT in the no anticoagulant group compared with low-dose DOACs (P<0.0001), but no significant difference between the low-dose and standard-dose DOACs (P=0.16) in the group without bleeding (see Figure 2). Conclusion Low-dose DOACs were found to be as effective as standard-dose DOACs in treating peripheral DVT in cancer patients, with or without bleeding of the cancer lesion. Peripheral DVT treatment with low-dose DOACs can reduce worsening of DVT and should be one of the supportive treatments for the completion of cancer management.DVT in 3 groups with cancer bleedingDVT in 3 groups without cancer bleeding

Abstract 12293: Subclinical Leaflet Thrombus on Transcatheter Heart Valve in Patients With Severe Aortic Stenosis and Atrial Fibrillation

Background: Subclinical leaflet thrombosis is one of transcatheter heart valve (THV) failure that should be avoided after transcatheter aortic valve implantation (TAVI). Although the effectiveness of direct oral anticoagulants (DOACs) on subclinical leaflet thrombosis has been demonstrated, there is insufficiently established evidence for post-TAVI antithrombotic therapy. The aim of this study was to clarify the formation process of subclinical leaflet thrombosis on THV and thrombogenicity during the perioperative period of TAVI. Methods: This multicenter, prospective, single-arm interventional study enrolled 26 patients with atrial fibrillation treated with edoxaban and severe aortic valve stenosis who underwent TAVI between September 2018 and September 2022. After exclusion, 24 patients were finally analyzed. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD). Results: Of all, subclinical leaflet thrombosis was observed in 16.7% at 1 week, but decreased to 5.9% at 3 months after TAVI. There was no significant difference in maximum leaflet thickness between 1 week and 3 months, however, patients with subclinical leaflet thrombosis at 1 week had a significantly greater difference in that thickness compared to those without thrombosis. Thrombogenicity assessed by T-TAS and platelet count decreased markedly at 1 week and tended to improve at 3 months. Simple liner regression analysis showed that stagnation volume was positively associated with an increase in maximum leaflet thickness, and low-dose edoxaban was associated with a high risk of increased leaflet thickness at chronic phase. Conclusions: This study showed that course of leaflet thrombus formation in neo-sinus of THV and dynamic fluctuation of thrombogenicity in the acute phase after TAVI. These findings were merely hypotheses generation and thus necessitate future hypothesis testing with large sample sizes.

Abstract 17888: Apixaban versus Vitamin K Antagonists for Left Ventricular Thrombus: A Systematic Review and Meta-Analysis

Introduction: Left ventricular thrombus (LVT), a major complication following acute myocardial infarction, significantly contributes to the increased risk of stroke and systemic embolism. Although vitamin K antagonists (VKAs) are the first-line treatment for LVT, direct oral anticoagulants (DOACs) have emerged as a potential alternative. However, the comparative effectiveness and safety of DOACs and VKAs for LVT treatment remain uncertain. Research question: Is apixaban therapy more effective and safer than VKA therapy for LVT? Aim: To assess the efficacy and safety of apixaban compared with VKAs therapy in patients with LVT. Methods: We systematically searched PubMed, Embase, and Cochrane databases for studies comparing the efficacy and safety of apixaban versus VKAs. We applied the random-effects model to calculate odds ratios (OR) and the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. All calculations and graphics were performed using R (version 4.2.3). Results: Three randomized clinical trials (RCTs) were included, with 109 patients assigned to either apixaban (56 patients) or VKAs (53 patients). Compared to VKAs, apixaban showed no significant impact on thrombus resolution (OR 0.69; 95% CI 0.11-4.50; p=0.70; I 2 =0%), stroke reduction (OR 0.91; 95% CI 0.09-9.38; p=0.93; I 2 =1%), clinically relevant bleeding (OR 0.21; 95% CI 0.02-1.99; p=0.17; I 2 =0%), or all-cause mortality (OR 0.65; 95% CI 0.11-3.78; p=0.63; I 2 =8%). Conclusions: Apixaban therapy showed similar efficacy and safety to VKAs for LVT. These findings support the use of apixaban as an alternative to VKAs in LVT treatment.

Extended Full Dose Versus Low Dose Direct Oral Anticoagulants in Cancer and Overweight Patients

Background: Reduced or low-dose direct oral anticoagulants (DOACs) have been studied in randomized control trials for the extended prevention of venous thromboembolism (VTE) after 6 months of treatment at full, therapeutic doses. The real-world effectiveness as well as utilization of this approach in clinical practice compared to continuing at therapeutic doses is unclear. Aims: Examine the effectiveness, safety and utilization of reduced-dose DOACs in cancer patients and overweight patients. Methods: Consecutive patients with VTE were identified using the Mayo Clinic VTE Registry from March 1st, 2013 to December 31st, 2021. Patients were followed prospectively for outcomes of VTE recurrence, death, major bleeding and clinically relevant non major bleeding (CRNMB) either in person or by survey. Patients with recurrent VTE or bleeding during the first 3 months were excluded from further analysis. After completion of anticoagulation treatment for 3 months with either rivaroxaban or apixaban, patients continuing anticoagulation were evaluated in a nested case-control study. Results: A total of 404 patients (283 (70%) on apixaban and 121 (30%) on rivaroxaban) were identified in the low dose DOAC and 3060 in the full dose anticoagulation group. Overall, the mean age was 60.7 years (SD 14.4), mean weight was 89.9 kg (SD 23.8) and 55.1% were males. Within the full cohort, patients with active cancer were less likely to be prescribed low dose DOACs (HR 0.56; 95%CI 0.42-0.73; p<0.001). However, low dose DOAC prescription was more likely in patients with pulmonary embolism alone (HR 1.48; 95%CI 1.21-1.80; p<0.001) or in combination with DVT (HR 1.54; 95%CI 1.25,1.90; p<0.001). Patients transitioned to low dose DOACs had similar age, sex and weight compared to the full dose anticoagulation group, however, fewer patients with weight ≥120 kg had reduced dosing (HR 0.68; 95%CI 0.46,0.99; p=0.046). The mean time to start of a low dose DOAC was 5.1 months overall, 5.4 months in cancer patients, and 3.6-4.9 months in non-cancer patients (Table 1). Non-cancer patients had significantly lower transition numbers in those ≥120kg (HR 0.62; 95%CI 0.40,0.97; p=0.038). In non-cancer patients In comparing weight, ≥120kg to <120kg, in the low dose group, only death was statistically different with higher risk in those ≥120kg (HR 6.44; 95%CI1.27,32.81; p=0.025). Cancer patients transitioned to low dose DOACs around 5 months on average with a median of 3.3 months. Apixaban continued to be the dominant DOAC used (78%) in the low dose group. The cancers with the most patients on low dose DOACs include lymphoma, prostate, melanoma, ovarian, and breast. There was no significant difference in VTE recurrence or death in the cancer group on different DOAC doses. Conclusion: Our results show that anticoagulant prescribers are not always waiting until 6 months to transition to low doses and low doses are being utilized in cancer patients despite lack of cancer-specific studies during the analyzed time period. Although the sample size limits the precision of this analysis, we did not find statistically significant increases in VTE recurrence with low dose DOACs in either cancer patients or with elevated body weight. We did find CRNMB but not MB was observed more frequently in weights above 120kg, possibly from unadjusted confounding in this unadjusted analysis.

Effect of antiplatelet and anticoagulant medication use on injury severity and mortality in patients with traumatic brain injury treated in the intensive care unit

BackgroundAntiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)–treated TBI patients with 1-year mortality and head CT findings.MethodWe conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003–2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality.ResultsOf 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02–2.58) and anticoagulants (OR 1.43, 95% CI 1.06–1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16–4.22) and anticoagulants (1.50, 95% CI 0.97–2.32) were associated with an increased risk of 1-year mortality.ConclusionsBoth antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU–treated TBI patients.

The Effect of Direct Oral Anticoagulants on Gastric Mucosa and Helicobacter Pylori Prevalence in Dyspeptic Patients: A Retrospective Cross-Sectional Study.

Backgroundand aim Although direct oral anticoagulants (DOACs) are widely used and their side effects related to bleeding at various body sites have been well studied in the literature, less is known about their local impact on gastric mucosa. Some studies suggest that the higher risk of gastrointestinal (GI) bleeding associated with DOACs may be due to their direct local anticoagulant effects on the gastric mucosa. In this study, we aim to evaluate whether this potential local effect has a favorable outcome on the gastric mucosa and the prevalence of Helicobacter pylori (HP). Materials and methods A total of 125 patients with dyspepsia were included in the study. Sixty patients who had been using a DOAC for at least one month were classified as the "DOAC group," while 65 patients who had not used DOACs were designated as the "control group." Demographic, laboratory, and pathological findings for these patients were retrospectively analyzed from their medical files. Results Patients in the DOAC group were significantly less likely to have antral gastritis (AnG) (p = 0.028), while the frequencies of HPand atrophic gastritis (AtG) were similar between the two groups. Although not statistically significant, the DOAC group showed fewer instances of intestinal metaplasia (IM) and a higher number of upper GI ulcers. Patients who had been using DOACs for more than 12 months had increased incidences of IM, upper GI ulcers, AnG, and HP compared to those who had been using DOACs for 12 months or less. The Rivaroxaban subgroup showed significantly lower HP positivity compared to patients using other DOACs (p = 0.042). Among all subgroups, the Rivaroxaban group had the lowest frequency of AnG (p = 0.024). Conclusion While DOACs seem to prevent AnG, HP, and IM at their early use stages, unfavorable gastric mucosa manifestations might increase with prolonged use. Higher upper GI ulcer prevalence is another controversial result of this issue. Rivaroxaban shines amongst other DOACs with its lesser HP and AnG association. These exciting findings should be supported by randomized controlled trials with large patient populations.

Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.

Direct Oral Anticoagulants (DOACs) have simplified the treatment of thromboembolic disease. In addition to their established anticoagulant effects, there are indications from clinical and preclinical studies that DOACs exhibit also non-anticoagulant actions, such as anti-inflammatory and anti-oxidant actions, advocating overall cardiovascular protection. In the present study, we provide a comprehensive overview of the existing knowledge on the pleiotropic effects of DOACs on endothelial cells (ECs) in vitro and their underlying mechanisms, while also identifying potential differences among DOACs. DOACs exhibit pleiotropic actions on ECs, such as anti-inflammatory, anti-atherosclerotic, and anti-fibrotic effects, as well as preservation of endothelial integrity. These effects appear to be mediated through inhibition of the proteinase-activated receptor signaling pathway. Furthermore, we discuss the potential differences among the four drugs in this class. Further research is needed to fully understand the pleiotropic effects of DOACs on ECs, their underlying mechanisms, as well as the heterogeneity between various DOACs. Such studies can pave the way for identifying biomarkers that can help personalize pharmacotherapy with this valuable class of drugs.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation in End-Stage Renal Disease on Hemodialysis: A Meta-Analysis of Randomized Control Trials

End-stage renal disease (ESRD) and atrial fibrillation (AF) are commonly encountered, with ESRD itself serving as a well-established risk factor for AF.1 The 2018 AF guidelines have recommended apixaban across all the spectrums of renal impairment, including patients on hemodialysis (HD), and the 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society updated guidelines have suggested careful consideration of reduced dose of direct oral anticoagulants (DOACs) in patients with ESRD.2,3 The current data on the safety and efficacy of warfarin versus DOACs in patients with AF with ESRD and HD is variable. This study aimed to perform a study-level meta-analysis to evaluate the effectiveness and safety of warfarin and DOACs in patients with AF who require dialysis.

Clinical benefits of oral anticoagulants in atrial fibrillation patients with dementia: a systematic review and meta-analysis.

The management of atrial fibrillation (AF) with oral anticoagulants (OAC) is generally recommended to reduce the risk of stroke. However, the decision to prescribe these medications for patients with AF and dementia remains controversial. A systematic review and meta-analysis of retrospective cohort studies were conducted. The search encompassed PubMed, Cochrane Library, Web of Science, and Embase databases from inception until May 1st, 2023, with language limited to English. Eligible studies included comparisons between exposure to OAC vs. non-OAC in the AF population with dementia or cognitive impairment. Studies that compared the effects of direct oral anticoagulants (DOAC) and vitamin-K antagonists were also included. The primary outcome was all-cause mortality, and the secondary outcomes were ischemic stroke and major bleeding. This study was registered with PROSPERO (No. CRD42023420678). A total of five studies (N = 21,962 patients) met the eligibility criteria and were included in this review. The follow-up duration ranged from 1 to 4 years. Meta-analysis demonstrated that OAC treatment was associated with a lower risk of all-cause mortality in AF patients with dementia with a hazard ratio (HR) of 0.79 and a 95% confidence interval (CI) ranging from 0.68 to 0.92, compared to non-OAC treatment. No statistical differences were observed in the risk of major bleeding (HR = 1.12, 95% CI: 0.88-1.42) or ischemic stroke (HR = 0.77, 95% CI: 0.58-1.00). Three studies reported comparisons between DOAC and warfarin; however, pooled analysis was not performed due to heterogeneity. The use of OACs in individuals diagnosed with both AF and dementia holds the potential to reduce all-cause mortality rates, thereby improving the overall clinical prognosis within this specific population. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420678, PROSPERO identifier, CRD42023420678.

Impact of Factor Xa Inhibition on Coagulation, Platelet Reactivity, and Thrombosis in Patients with Peripheral Artery Disease

The role of thrombin in vascular pathology is a focus of investigation. The incorporation of direct Factor Xa inhibition into practice patterns is based on its theoretical dual-pathway attenuation of both thrombin generation and platelet aggregation. However, quantification of the effect of direct anti-Xa medications on platelet function is not established. Thromboelastography with platelet mapping (TEG-PM) leverages dual-pathway metrics to provide comprehensive coagulation profiles. We evaluated the effects of direct oral anticoagulants (DOACs) on coagulation and platelet function profiles and correlate these data with postoperative major adverse limb events (MALEs) in patients with PAD. We conducted a prospective study of patients undergoing lower extremity revascularization with serial perioperative TEG-PM analysis. Patients on DOACs were compared to those not on DOACs, and stratified by concurrent mono-antiplatelet or dual-antiplatelet regimens (MAPT/DAPT). Postoperative MALE was recorded and difference in antithrombotic regimens and TEG-PM analysis compared between groups. Four hundred seventy-one samples from 141 patients were analyzed. Twenty-nine point five percent were reflective of circulating DOAC therapy. Compared to MAPT alone, patients on DOAC+MAPT exhibited longer time to clot formation (R-time) [7.4 (±2.4) vs. 6.7 (±2.7); P<0.02], but less platelet inhibition. Patients on DAPT exhibited greater platelet inhibition compared to either group [23.7 (±26.9) vs. 31.0 (±28.3) vs. 42.2 (±31.2); P<0.01]. Patients who experienced MALE were more likely to be on DOAC therapy [43.8% vs. 22.0% P=0.02]. Thromboelastography with platelet mapping analysis from patients who experienced MALE also demonstrated longer R-time [8.6 (±3.9 vs. 7.3 (±3.0); P=0.05] and increased maximum clot amplitude (MA) [66.7 (±4.2) vs. 61.8 (±8.2); P=0.001]. Direct oral anticoagulant therapy resulted in a prolonged R-time but had no impact on platelet inhibition. Patients who experienced MALE were more often on DOACs and demonstrated an increased R-time, but also showed greater platelet reactivity evident by increased MA, suggesting DOACs may not be effective at protecting against MALE. Further research comparing DOAC therapy to a DAPT approach may add clarity to emerging multimodal antithrombotic recommendations.

Direct oral anticoagulants in general practice

Nurses prescribing these medications, used for stoke prevention in atrial fibrillation in general practice, must understand the risks surrounding them. This article outlines indications, side effects and monitoring. Four direct oral anticoagulants (DOACs) are available in the UK and appear in National guidance as first line treatment for VTE and stroke prevention in atrial fibrillation. They provide a more practical option than warfarin, with similar efficacy and safety profiles, with the additional advantage of significantly reduced risk of intracranial haemorrhage (Raschi et al 2016). DOACs are not suitable for patients with mechanical heart valves, antiphospholipid syndrome or for women who are pregnant or breastfeeding. DOACs work by inhibiting a single clotting factor, meaning their effects are more predictable than warfarin which works on several clotting factors. Bleeding is the main side effect and safety consideration of DOACs, with major bleeding occurring in around 1-4% of people taking DOACs ( Hellenbart et al 2017 ). Careful risk assessment, patient counselling and at least annual review of patients on DOACs can help to reduce their associated risks.

Current insights into the possible role of laboratory monitoring of effectiveness and safety of direct oral anticoagulants

The article is devoted to the discussion of modern approaches to the use of laboratory methods to improve the tactics of using direct oral anticoagulants (DOACs) therapy. Clinical situations in which it may be reasonable to use data on the blood concentration of DOACs are given, including very old age, a marked deviation from the norm of body weight or impaired renal function. Data on the role of measuring the blood level of DOACs are considered in cases of the development of diseases or complications in which information is required on the preservation of the anticoagulant effect of DOACs, for example, in the development of severe bleeding or the need for urgent surgical intervention. The advantages and limitations of modern laboratory methods for assessing the blood concentration of DOACs are discussed. It is emphasized that one of the main advantages of using DOACs is the absence of the need to monitor laboratory parameters in most patients. Data from pharmacological studies are presented that may be useful in explaining the mechanisms that determine the higher safety of some DOACs compared to others. Promising methods for assessing the blood level of DOACs, as well as the possibility of using less specific reagents for assessing the concentration of DOACs, are considered. The possibility of using less specific, but more accessible methods for assessing the blood concentration of factor Xa inhibitors, in particular, a reagent for assessing the level of the antifactor, which is used to determine the blood level of heparin, is being considered. The opinions of experts on the role of assessing the blood level of DOACs and the possibility of tactics for selecting doses of DOACs based on laboratory analysis data are given.

Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism.

Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center. This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE. A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban. Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.

DOACs use in extreme body-weighted patients: results from the prospective START-register.

Direct oral anticoagulants (DOACs) are widely used for the treatment of venous thromboembolism (VTE) and for stroke prevention in atrial fibrillation (AF). However, evidence in obese and underweight patients is limited. We assessed the safety and effectiveness of DOACs and vitamin K antagonists (VKAs) in patients ≥ 120kg or ≤ 50kg enrolled in an observational prospective cohort study, the START-Register. Adult patients started on anticoagulant therapy were followed up for a median of 1.5years (IQR 0.6-2.8). Primary efficacy outcome was the occurrence of VTE recurrence, stroke and systemic embolism. Primary safety outcome was major bleeding (MB). 10,080 AF and VTE patients were enrolled between March 2011 and June 2021, 295 patients weighted ≤ 50kg and 82 patients ≥ 120kg. Obese patients were significantly younger than underweight patients. Rates of thrombotic events were low and similar between DOACs and VKAs in underweight patients (1 event on DOACs therapy [0.9% 95% CI 0.11-5.39] and 2 on VKAs [1.1% 95% CI 0.01-47.68]) and in overweight patients (0 events on DOACs, 1 on VKAs [1.6%, 95% CI 0.11-5.79]. Two MB events occurred on DOACs (1.9%, 95% CI 0.38-6.00) and 3 on VKAs (1.6%, 95% CI 0.04-22.06) in the underweight group; 1MB on DOACs (5.3% 95% CI 0.33-16.68) and 2 on VKAs (3.3%, 95% CI 0.02-130.77) in the overweight group. DOACs seem to be effective and safe also for the treatment of patients with extreme body weights, both underweight and overweight. Further prospective studies are needed to support these findings.

Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism.

To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT). In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable. Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.

Comparison of oral anticoagulation by vitamin-K antagonists and non-vitamin-K antagonists for treatment of leaflet thickening after transcatheter aortic valve implantation (TAVI)

IntroductionHypoattenuated leaflet thickening (HALT), as identified by CT imaging, is not infrequent after transcatheter aortic valve implantation (TAVI). The best choice of oral anticoagulation is unknown. We compared the effectiveness of Direct Oral AntiCoagulants (DOAC) and Vitamin-K Antagonists (VKA) to resolve HALT in patients with serial CT aquisitions. MethodsA total of 46 consecutive TAVI patients in whom anticoagulation had been initiated because of HALT and who underwent follow-up CT were identified. Indication and type of anticoagulation was according to physician discretion. Patients on DOAC were compared to VKA therapy regarding resolution of HALT. ResultsMean age of the 46 patients was 80 ± 6 years (59% men), and the mean duration of anticoagulation was 156 days. Overall, 41 patients (89%) showed resolution of HALT with anticoagulation therapy, whereas HALT persisted in 5 patients (11%). Resolution of HALT was seen in 26 out of 30 (87%) patients receiving VKA and in 15 out of 16 (94%) patients receiving DOAC, respectively. Groups did not differ regarding age, cardiovascular risk factors, TAVI prosthesis type and size or duration of anticoagulation (all p > 0.05). ConclusionAnticoagulation therapy resolves leaflet thickening after TAVI in most patients. Non-Vitamin-K antagonists seem to be an effective alternative to Vitamin-K antagonists. This finding needs to be confirmed in larger prospective trials.

Aortic Stenosis and Outcomes in Patients With Atrial Fibrillation: A Nationwide Cohort Study.

Background Patients with aortic stenosis (AS) have been underrepresented in the trials evaluating direct oral anticoagulants (DOACs) in atrial fibrillation (AF). We aimed to assess whether AS impacts outcomes in patients with AF and estimate the effects of DOACs versus warfarin in patients with AF and AS. Methods and Results The registry-based FinACAF (Finnish Anticoagulation in Atrial Fibrillation) study covered all patients with AF diagnosed during 2007 to 2018 in Finland. Hazard ratios (HRs) of first-ever gastrointestinal bleeding, intracranial bleeding, any bleeding, ischemic stroke, and death were estimated with cause-specific hazards regression adjusted for anticoagulant exposure variables. We identified 183 946 patients (50.5% women; mean age, 71.7 [SD, 13.5] years) with incident AF without prior bleeding or ischemic stroke, of whom 5231 (2.8%) had AS. The crude incidence rate of all outcomes was higher in patients with AS than in patients without AS. After propensity score matching, AS was associated with the hazard of any bleeding, gastrointestinal bleeding, and death but not with intracranial bleeding or ischemic stroke (adjusted HRs, 1.36 [95% CI, 1.25-1.48], 1.63 [95% CI, 1.43-1.86], 1.32 [95% CI, 1.26-1.38], 0.96 [95% CI, 0.78-1.17], and 1.11 [95% CI, 0.99-1.25], respectively). Among patients with AS, DOACs were associated with a lower risk of ischemic stroke when compared with warfarin, while bleeding and mortality did not differ between DOACs and warfarin. Conclusions AS is associated with substantially higher risk of gastrointestinal bleeding in patients with AF. DOACs may be more effective in preventing ischemic stroke than warfarin in patients with AF and AS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04645537.

Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. ObjectivesThe CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. Patients/MethodsPatients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. ResultsNine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). ConclusionThis registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Is There a Role for Vitamin K Antagonist in the Management of Atrial Fibrillation in 2023?

To address the following question: Are vitamin K antagonists (VKA) obsolete as stroke prevention therapy for patients with atrial fibrillation (AF) and thromboembolic risk factors? A patient-level meta-analysis of the pivotal phase III randomized trials confirmed the favorable treatment effect of direct oral anticoagulants (DOAC) over VKA in multiple key patient subgroups. Among patients with AF and rheumatic heart disease (85% of whom had mitral stenosis), a randomized trial showed that rivaroxaban was not superior to VKA for stroke prevention. Caution should be exercised when prescribing DOAC for AF-related stroke prevention for patients with elevated body mass indices or history of bariatric surgery, patients with bioprosthetic heart valves, and those who require treatment with drugs that interact with cytochrome P450 and P-glycoprotein. Drug costs associated with DOAC remain considerably higher than VKA, by up to 30-fold. Direct oral anticoagulants are preferable over VKA in the large majority of eligible patients with AF and thromboembolic risk factors. The use of DOAC should be avoided for patients with mechanical heart valves or moderate/severe rheumatic mitral stenosis. Vitamin K antagonist is a reasonable option for patients who are under-represented in randomized trials, when there are significant drug-drug interactions or when patients cannot afford DOAC agents due to their higher costs.