Direct Oral Anticoagulants Treatment Research Articles

Before, during, and after: An Argument for Safety and Improved Outcome of Thrombolysis in Acute Ischemic Stroke with Direct Oral Anticoagulant Treatment.

Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke. ANN NEUROL 2024;96:871-886.

Haemorrhagic risk in elderly patients with atrial fibrillation that develop low platelet count during direct oral anticoagulant treatment: insights from the ATHERO-AF study

Abstract Background Bleeding risk in atrial fibrillation (AF) patients is complex and dynamic. Among others, thrombocytopenia has been suggested as a bleeding risk factors. No data on thrombocytopenia occurring during direct oral anticoagulants (DOACs) therapy are available. Purpose We investigated the incidence rate of thrombocytopenia and major bleeding (MB) in AF patients on DOACs. We also investigated whether the addition of incident thrombocytopenia to the HAS-BLED score might increase its predictive value compared to baseline HAS-BLED calculation. Methods 955 AF patients from the prospective ongoing ATHERO-AF study followed for a mean of 38.4±26.6 months. All patients were on DOACs. Thrombocytopenia was defined by a platelet count <150 x109/L registered during follow-up visits. MB events were defined according to ISTH definition and were recorded at each follow-up visit. Patients with thrombocytopenia at baseline were excluded. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to bleeding risk. Results Mean age was 77.3±9.0 years and 40.1% were women. During a follow-up, 139 patients developed thrombocytopenia with an incidence rate of 0.8% per year. We recorded no difference between thrombin and factor Xa inhibitors. During follow-up, 179 bleedings occurred, of which 80 were major. Patients experiencing bleedings were more likely to suffer from arterial hypertension, heart failure, anaemia and had higher CHA2DS2-VASc and HAS-BLED scores. At multivariable Cox proportional hazards regression analysis, factors associated with MB were incident thrombocytopenia (HR 1.995, 95%CI 1.211-3.288), antiplatelet use (HR 2.716 95%CI 1.269-5.816) and age (HR 1.033, 95%CI 1.003-1.064). The addition of incident thrombocytopenia to the HAS-BLED score increased the predictive value of baseline HAS-BLED in patients without thrombocytopenia for MB events (AUC from 0.54 to 0.61, p=0.016). Conclusion Incident thrombocytopenia is associated with an increased risk of MB. The addition of incident thrombocytopenia to the baseline HAS-BLED score increased its predictive value, suggesting that continuous bleeding risk evaluation of AF patients may provide additional prognostic information compared to the baseline only.

Comparative analysis of vitamin K antagonists and direct oral anticoagulants for left ventricular thrombus management: a retrospective study utilising TriNetX

Abstract Introduction Despite progress in cardiovascular medicine, guidelines for addressing left ventricular thrombus (LVT) remain limited. Furthermore, incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction (MI) adds complexity to treatment decisions. While conventional guidance favors vitamin K antagonists (VKAs), emerging evidence suggests favorable outcomes with direct oral anticoagulants (DOACs). Purpose This study aims to assess the safety and efficacy of DOACs versus VKAs in managing LVT among patients with and without recent acute coronary syndrome (ACS). Methods This was a retrospective observational study conducted within TriNetX, a global federated health research network with access to electronic medical records (EMRs) from participating health care organizations including academic medical centres and community hospitals covering approximately 70 million individuals, mainly in the United States. The search was conducted on 26th Februrary 2024 with a study cohort comprising patients with LV thrombus treated with either DOAC or VKA between 1st December 2013 to 1st December 2023. Subgroup analyses were conducted for patients with ACS within one month and those without ACS within a month of treatment. Cohort data were subject to propensity matching (PSM) for age, gender, ethnicities, medical and drug history. Risk analysis and Kaplan-Meier survival analysis were computed for each subgroup at 90 days since the indexed event. Results Following PSM, a total of 39,770 patients were included and 14,302 were in the ACS group and 24,162 in the non-ACS group. DOAC treatment exhibited favourable outcomes for stroke, bleeding, and systemic embolism (p<0.05) compared to VKA in the overall cohort (Table 1). In the ACS group, DOAC was linked to a reduced risk of stroke and systemic embolism (p<0.05) but not bleeding (p=0.066). In the non-ACS group, DOAC was associated with a decreased risk of stroke and bleeding (p<0.05) but not systemic embolism (p=0.113). Across all groups, there were no disparities in overall all causes of mortalities. Conclusion DOACs demonstrated better safety and efficacy outcomes when compared to VKAs in LVT treatment. Interestingly, DOACs utilisation within the ACS context resulted in a diminished risk of embolic complications without the benefit of reduced bleeding risk seen in patients without ACS, suggesting potential implications of triple therapy within first month of ACS treatment, removing the bleeding risk reduction of DOACs. This shows a fundamental difference in LVT between the 2 groups of patients so future studies should aim to differentiate between the 2.

Black hole sign under anticoagulant therapy: A retrospective comparison of warfarin and direct oral anticoagulants.

Direct oral anticoagulants (DOAC) have rapidly replaced warfarin. Intracerebral hemorrhage (ICH) is known to be one of the most severe side effects of anticoagulant drugs. The black hole (BH) sign is reportedly a valid radiological sign for predicting hematoma expansion in acute ICH. Here, we hypothesized that the frequency of BH signs might differ between warfarin and DOAC treatment, and critically evaluated the clinical value of the BH sign in acute ICH under warfarin versus DOAC therapy. Patients with acute ICH under anticoagulant therapy were enrolled. Hematoma volumes were measured by ABC/2. Radiologists blinded to the clinical information determined the presence or absence of the BH sign on CT images. This study defined a more than 12.5 ml increase in hematoma volume as cases with "expanded hematoma". We analyzed 111 acute ICH patients under anticoagulant therapy. Among them, 21 patients were treated with antagonists in this cohort. Multivariate logistic regression analysis revealed that the presence of ventricular perforation (p=0.02; adjusted odds ratio (OR): 3.51, 95% confidence interval (CI): 1.32 - 10.2) and the BH sign (p<0.01; adjusted OR: 4.86, 95% CI: 1.73 - 14.3) were significantly different between expanded and non-expanded hematoma cases. Comparison of hematoma volume and the presence of the BH sign between warfarin and DOAC cases indicated significant differences in maximum hematoma volume (p=0.03) and presence of the BH sign (p<0.01). The increase in hematoma volume was significantly greater when the BH sign was present under warfarin therapy (p=0.05). In contrast, the increase in hematoma volume did not differ between cases with and without the BH sign in patients under DOAC therapy (p=0.14) CONCLUSIONS: The BH sign is a useful radiological signature to predict the expansion of acute ICH under anticoagulant therapy. ICH under warfarin tended to present the BH sign more frequently than that under DOAC. The results also showed that the BH sign is more reliable under warfarin than under DOAC therapy in ICH patients. AF = atrial fibrillation; BH = black hole; DOAC = direct oral anticoagulants; HU = Hounsfield Unit; ICH= intracerebral hemorrhage.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5mg BID or rivaroxaban 10mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14-p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

Direct Oral Anticoagulants and Bleeding Management Following Tooth Extractions-A Prospective Cohort Study.

The aim of the present study was to assess the occurrence of intra-, peri-, and post-operative bleeding following tooth extractions in patients treated with direct oral anticoagulants (DOACs). Consecutive patients requiring at least one dental extraction were enrolled. The DOAC regimen was either maintained or suspended. Patients were classified in subgroups depending on the number of teeth extracted per procedure (≤3 or >3), the need for flap elevation, and the performance of osteotomy. Bleeding was recorded intra-operatively; peri-operatively at 20, 40, 60, and 80 min after the procedure; and daily in the first seven days following tooth extractions. Forty-nine patients treated with DOACs (17 with rivaroxaban, 16 with apixaban, 8 with edoxaban, and 8 with dabigatran) were enrolled. Of them, 33 refrained from DOAC administration pre-operatively. The performances of >3 teeth extractions, flap elevation, and osteotomy were significantly associated with higher bleeding rates (p < 0.05). In patients treated with rivaroxaban and apixaban, bleeding episodes were more frequent. Although DOAC treatment may increase the rates of intra-operative, peri-operative, and post-operative bleeding, the recorded episodes were mild and manageable. DOAC suspension may reduce peri-operative bleeding, while no effect could be observed for post-operative bleeding.

Stroke in women: anticoagulation in a complicated puzzle

Stroke is the third leading cause of death and the most important reason for disability. It is worth noting that 60% of all stroke deaths involve women. This review aims to revise the prothrombotic hemostatic alterations in hypertension along with the often-overlooked role of depression and the job strain of the homemakers’ condition proven to be risk factors for stroke. Moreover, the impact of atrial fibrillation and the related oral anticoagulation with either vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) in women will be discussed. Another point is that women are treated less with anticoagulants than men. Underdosing is also frequent. In our opinion, defensive medicine represents the basic bias, which plays a major role in this contest. The main reasons are the overlooking of the increased cardioembolic risk in women, the fear of an increased bleeding risk, and the wrong concept regarding a hypothetical higher frailty. In conclusion, from a practical point of view, thrombosis centers should consider all these factors when a woman shows a bad quality of anticoagulation with VKA or a poor adherence to DOAC treatment. Underdosing should also be carefully avoided. We hope that the sex gap in terms of inadequate treatment and inclusion in clinical trials will be covered in the future. Lastly, defensive medicine should be strongly discouraged.

Effectiveness and safety of continuous low-molecular-weight heparin versus switching to direct oral anticoagulants in cancer-associated venous thrombosis

Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35–0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61–0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83–1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.

Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment.

Overdosing of direct oral anticoagulants

Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality. This article aims at raising awareness of DOAC overdosing and its causes as well as presenting adiagnostic and therapeutic work-up. Based on acase presentation, astructured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted. In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options. The sensitization of clinicians is important to ensure atimely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.

Proactive monitoring of drug–drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer

BackgroundSmall-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug–drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs.MethodsThis prospective, observational study enrolled patients with NSCLC concomitantly using a DOAC and SMI. The primary outcome was the proportion of patients with DOAC plasma trough (Ctrough) and peak (Cpeak) concentrations outside expected ranges. Secondary outcomes included DOAC treatment modifications, incidence of bleeding and thromboembolic events and feasibility evaluation of pharmacokinetically guided DOAC dosing.ResultsThirty-three patients were analysed. Thirty-nine percent (13/33) had DOAC Ctrough and/or Cpeak were outside the expected ranges in 39% (13/33). In 71% (5/7) of patients with DOAC concentrations quantified before and during concurrent SMI use, DOAC Ctrough and/or Cpeak increased or decreased >50% upon SMI initiation. In all patients in whom treatment modifications were deemed necessary, DOAC concentrations were adjusted to within the expected ranges.ConclusionProactive monitoring showed that a substantial proportion of patients had DOAC concentrations outside the expected ranges. DOAC concentrations were successfully normalised after treatment modifications. These results highlight the importance of proactive monitoring of DOAC-SMI DDIs to improve treatment in patients with NSCLC.

The serum metabolomic profiles of atrial fibrillation patients treated with direct oral anticoagulants or vitamin K antagonists

AimsLong-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Materials and methodsSerum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches. Key findingsOur data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs ∼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40–0.51) are characteristic of serum profile of patients on DOACs' therapy. SignificanceOur results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.

Circulating microRNAs and DNA Methylation as Regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation and Key Elements for the Identification of the Mechanism of Action (miR-CRAFT): Study Design and Patient Enrolment.

Direct oral anticoagulants (DOACs) are the standard treatment for thromboembolic protection in atrial fibrillation (AF) patients. Epigenetic modifications, such as DNA methylation and microRNAs, have emerged as potential biomarkers of AF. The epigenetics of DOACs is still an understudied field. It is largely unknown whether epigenetic modifications interfere with DOAC response or whether DOAC treatment induces epigenetic modifications. To fill this gap, we started the miR-CRAFT (Circulating microRNAs and DNA methylation as regulators of Direct Oral Anticoagulant Response in Atrial Fibrillation) research study. In miR-CRAFT, we follow, over time, changes in DNA methylation and microRNAs expression in naïve AF patients starting DOAC treatment. The ultimate goal of miR-CRAFT is to identify the molecular pathways epigenetically affected by DOACs, beyond the coagulation cascade, that are potentially mediating DOAC pleiotropic actions and to propose specific microRNAs as novel circulating biomarkers for DOAC therapy monitoring. We herein describe the study design and briefly present the progress in participant enrolment.

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

Direct Oral Anticoagulants for Pulmonary Embolism.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. For most patients, the standard of treatment has long consisted on low-molecular-weight heparin followed by vitamin K antagonists, but a number of clinical trials and, subsequently, post-marketing studies have shown that direct oral anticoagulants (DOACs) with or without lead-in heparin therapy are effective alternatives with fewer adverse effects. This evidence has led to important changes in the guidelines on the treatment of VTE, including pulmonary embolism (PE), with the DOACs being now recommended as the first therapeutic choice. Additional research has contributed to identifying low-risk PE patients who can benefit from outpatient management or from early discharge from the emergency department with DOAC treatment. There is evidence to support the use of DOACs in intermediate-risk PE patients as well as in high-risk patients receiving thrombolytic treatment. The use of DOACs has also been proven to be safe and effective in special populations of PE patients, such as patients with renal impairment, liver impairment, and cancer.

Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillation: the MAS study

AbstractAlthough effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve treatment efficacy is an open issue. We carried out the observational, prospective, multicenter Measure and See (MAS) study. Blood was collected 15 to 30 days after starting DOAC treatment in patients with AF who were followed-up for 1 year. Plasma samples were centralized for DOAC level measurement. Patients’ DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. In total, 21 thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% of patients per year). Of 21 thrombotic events, 17 occurred in patients whose standardized activity levels were below the mean of each DOAC (0); the incidence was the highest (4.82% of patients per year) in patients whose standardized values were in the lowest class (−1.00 or less). Early measurement of DOAC levels in patients with AF allowed us to identify most of the patients who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated. This trial was registered at www.ClinicalTrials.gov as #NCT03803579.

Effect of direct oral anticoagulants on bleeding during and after cataract surgery

PurposeTo assess the risk for intraoperative and postoperative ocular bleeding associated with direct oral anticoagulant treatment in patients undergoing phacoemulsification surgery.MethodsConsecutive patients had phacoemulsification and intraocular lens implantation while taking uninterrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban). Gender and age-matched patients without antithrombotic therapy were used as the control group. Patients were examined one week postoperatively. Intraoperative and postoperative hemorrhagic and non-hemorrhagic complications were assessed.ResultsForty patients (56 eyes) on direct oral anticoagulants and 120 patients (172 eyes) without anticoagulation, at a mean age of 77 years, had phacoemulsification. There was no significant difference between the groups in the rate of intraoperative and postoperative bleeding. One eye (1.8%) in the treatment group and 3 eyes (1.7%) in the control group had hyphema (p = 0.72). No patient had thromboembolic event during or after surgery.ConclusionsCataract surgery was safely performed while continuing direct oral anticoagulation.

Acute Ischaemic Stroke in Patients Treated with Direct Oral Anticoagulants: Potential Causes, Clinical Characteristics, and Short-Term Outcomes.

Direct oral anticoagulants (DOAC) are the first-line treatment for primary and secondary acute ischaemic stroke (AIS) prevention in patients with nonvalvular atrial fibrillation (NVAF), but a significant percentage of patients develop AIS despite being treated with DOAC. As the number of DOAC-treated patients is growing, so is the number of patients with AIS on DOAC. The aim of the study was to assess the incidence of AIS with prestroke DOAC treatment among patients hospitalised in the University Hospital in Kraków, to analyse the clinical characteristics of AIS occurring in patients on DOAC, and to identify potential causes of treatment ineffectiveness in this group. In the study, we included all patients hospitalised in the Department of Neurology of the University Hospital in Kraków within one year (July 2022 to June 2023) with the diagnosis of AIS. The group was divided into two subgroups of patients with and without prestroke DOAC treatment. Based on medical files, we retrospectively analysed the profile of cardiovascular risk factors, stroke severity (assessed with National Institutes of Health Stroke Scale, NIHSS), use of causative stroke treatment and short-term outcomes (defined as NIHSS score, modified Rankin scale (mRS) score at discharge, in-hospital mortality, and secondary intracerebral haemorrhage among patients treated with mechanical thrombectomy, MT). Within the DOAC-treated subgroup, we looked for potential causes of AIS occurring despite DOAC treatment (valvular AF, poor adherence to treatment, underdosing, other prothrombotic conditions, aetiology of stroke other than thromboembolic, and drug-drug interactions). In the study, we included 768 AIS patients. 109 (14.2%) had a history of prestroke DOAC treatment. A potential cause of DOAC treatment failure was identified in the majority of them (n = 63, 57.8%). Patients with prestroke DOAC treatment had worse functional condition before stroke and higher stroke severity on admission but similar short-term outcomes and similar short-term effects of treatment with MT. DOAC (+) and DOAC (-) patients had different profiles of cardiovascular risk factors and different factors associated with short-term outcome. Conclusions and Clinical Implications. A potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

BackgroundWe investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.MethodsThis is an individual patient...