OBJECTIVE: Patients with thromboembolic problems, prosthetic valves, or coagulation issues are commonly prescribed anticoagulants and antiplatelets. Anticoagulant and antiplatelet medication might constitute a challenge for dentists and dental hygienists since possible prolonged bleeding might interfere with dental procedures. The aim of the present study was to examine the bleeding durations associated with various anticoagulants and antiplatelets during professional dental hygiene sessions, utilizing a modified Ivy test adapted for the oral context.
METHODS: Ninety-three consecutive patients undergoing professional oral hygiene were recruited. Debridement during oral hygiene was performed using ultrasonic mechanical instrumentation, and bleeding sites were assessed and treated with gentle pressure using sterile gauzes. The time for bleeding cessation was recorded. Patients were categorized into six groups based on their drug intake, Control: no anticoagulants or antiplatelets DTI: direct thrombin inhibitors (dabigatran) AntiXa: directa factor Xa inhibitors (endoxaban, apixaban, rivaroxaban) VKA: vitamin K antagonists (warfarin, acenocoumarol) SAPT: single anti-platelet therapy (acetylsalicylic acid or clopidogrel) DAPT: dual anti-platelet therapy (acetylsalicylic acid and clopidogrel). Bleeding time was measured in seconds and mean values were assessed among the different groups. Differences between groups were investigated with Kruskal-Wallis test followed by Dunn\'s post-hoc correction for multiple comparisons or two-way ANOVA followed by Dunnett post-hoc; RESULTS: Control patients presented the lowest bleeding time 50 s, followed by AntiXa (98), SAPT (105), DTI (120), DAPT (190) and VKA (203). A statistically significant difference was present among control and DTI (p = 0.004), VKA (p < 0.001), DAPT (p < 0.001).
CONCLUSIONS: Based on the present outcomes, an increased risk of prolonged bleeding emerged in patients taking VKA and DAPT.
CONCLUSIONS: bleeding did not interfere with the oral hygiene session The optimal period for dental treatment of these patients should be 2-3 h before the next dose, without the need to temporarily suspend the medication.

Therapeutic plasma exchange (TPE) is used as an effective treatment modality for a variety of autoimmune disorders. Apart from its desired effect of removing pathological blood components, it also can remove coagulation factors and drugs. Currently, there is an insufficient amount of information regarding the use of direct oral anticoagulants in this setting. In this article, we present a case report of a patient with myasthenia gravis and chronic anticoagulation with apixaban who underwent a series of TPE while continuing apixaban treatment. We observed that only 10% of daily dose was removed by the procedure and plasma levels of apixaban corresponded with expected range. TPE was not associated with shortened drug plasma half-life. We did not observe any significant alteration of apixaban pharmacokinetics during the period of TPE therapy, as well as no thrombotic or bleeding events. This case report supports the use of apixaban in patients treated by TPE, nevertheless, to firmly establish apixaban efficacy and safety profile in this clinical setting further research is needed.

DIE AKTUELLEN LEITLINIENEMPFEHLUNGEN ZUR BEHANDLUNG VON VENöSEN THROMBEMBOLIEN BEI PATIENT:INNEN MIT EINER AKTIVEN MALIGNOMERKRANKUNG UNTERSTüTZEN DIE GABE VON DIREKTEN ORALEN ANTIKOAGULANZIEN ALS ALTERNATIVE ZU NIEDERMOLEKULAREN HEPARINEN (NMH). DIE WISSENSCHAFTLICHE EVIDENZ FüR DIESES VORGEHEN WAR BISHER ALLERDINGS NICHT SEHR GUT. EINE KOHORTENSTUDIE AUS GROßBRITANNIEN ZEIGTE JETZT, DASS DIE EFFEKTIVITäT UND SICHERHEIT VON RIVAROXABAN VERGLEICHBAR ZUM STANDARDVORGEHEN IST.

BACKGROUND: Limited real-world evidence is available comparing the safety and effectiveness of apixaban and low-molecular-weight heparins (LMWHs) for preventing recurrent venous thromboembolism (VTE) in patients with active cancer receiving anticoagulation in an extended treatment setting. This study evaluated the risk of bleeding and recurrent VTE in patients with cancer-associated VTE who were prescribed apixaban or LMWH for ≥3 months.
METHODS: A US commercial claims database was used to identify adult patients with VTE and active cancer who initiated apixaban or LMWH 30 days following the first VTE diagnosis and had ≥3 months of continuous enrollment and 3 months of primary anticoagulation treatment. Patients were followed from the day after the end of primary anticoagulation treatment until the earliest of: date of disenrollment, discontinuation of index anticoagulant, switch to another anticoagulant, or end of the study period. Inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Incidence rates (IRs) for the outcomes were calculated per 100 person-years (PY). Cox proportional hazard models were used to evaluate the adjusted risk of recurrent VTE, major bleeding (MB), and clinically relevant nonmajor bleeding (CRNMB).
RESULTS: A total of 13,564 apixaban- and 2,808 LMWH-treated patients were analyzed. Post-IPTW, the treatment cohorts were balanced. Patients receiving apixaban had lower adjusted IRs for recurrent VTE (4.1 vs 9.6 per 100 PY), MB (6.3 vs 12.6), and CRNMB (26.1 vs 36.0) versus LMWH (P<.0001 for all comparisons) during the follow-up period. Patients on apixaban had a lower adjusted risk of recurrent VTE (hazard ratio [HR], 0.42; 95% CI, 0.34-0.53), MB (HR, 0.50; 95% CI, 0.41-0.61), and CRNMB (HR, 0.76; 95% CI, 0.68-0.85) versus LMWH.
CONCLUSIONS: Extended anticoagulation treatment of ≥3 months with apixaban was associated with lower rates of recurrent VTE, MB, and CRNMB compared with LMWH in adults with cancer-associated VTE.

OBJECTIVE: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban.
METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels.
RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations.
CONCLUSIONS: Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.

BACKGROUND: Atrial fibrillation (AF) is prevalent among patients with end-stage kidney disease (ESKD) undergoing dialysis, and both conditions are associated with a heightened risk of cardiovascular diseases. Anticoagulation is essential for preventing thromboembolic complications in these patients. This study aimed to evaluate the effects of factor Xa inhibitors compared to vitamin K antagonists (VKAs) for AF patients on dialysis.
METHODS: A comprehensive search of PubMed and Embase databases was conducted to identify relevant studies published up to June 2024. Eligible studies compared factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with VKAs in AF patients on dialysis, with primary outcomes of stroke or systemic embolism(SSE) and major bleeding.
RESULTS: A total of 7 studies (3 randomized controlled trials and 4 observational cohorts) were included. For the RCTs, the use of factor Xa inhibitors was associated with a reduced risk of SSE compared to VKAs (odds ratio [OR] = 0.37, 95% confidence interval [CI]:0.15-0.93). There was no significant difference in the risk of major bleeding events between the two groups (OR = 0.65, 95%CI:0.32-1.33). Observational cohort studies yielded similar results with a decreased risk of SSE (hazard ratio [HR] = 0.74, 95%CI:0.57-0.96) and no significant difference in major bleeding (HR = 0.87, 95%CI:0.62-1.22). No differences in treatment effect between apixaban and rivaroxaban were observed for efficacy (p-interaction = 0.44) and safety (p-interaction = 0.21) outcomes.
CONCLUSIONS: Factor Xa inhibitors, particularly apixaban and rivaroxaban, were associated with a lower risk of SEE without an increase in major bleeding, which might be convenient alternatives to VKAs in managing AF in patients with ESKD on dialysis.

BACKGROUND: Patients with atrial fibrillation and severe chronic kidney disease have higher risks of bleeding, thromboembolism, and mortality. However, optimal anticoagulant choice in these high-risk patients remains unclear.
RESULTS: Using deidentified electronic health records from the Optum Labs Data Warehouse, adults with atrial fibrillation and severe chronic kidney disease (estimated glomerular filtration rate <30 mL/min per 1.73 m2) initiating warfarin, apixaban, or rivaroxaban between 2011 and 2021 were included. Using inverse probability of treatment weighting, adjusted risks of major bleeding, stroke/systemic embolism, and death were compared among agents. A total of 6794 patients were included (mean age, 78.5 years; mean estimated glomerular filtration rate, 24.7 mL/min per 1.73 m2; 51% women). Apixaban versus warfarin was associated with a lower risk of major bleeding (incidence rate, 1.5 versus 2.9 per 100 person-years; subdistribution hazard ratio [sub-HR], 0.53 [95% CI, 0.39-0.70]), and similar risks for stroke/systemic embolism (incidence rate, 1.9 versus 2.4 per 100 person-years; sub-HR, 0.80 [95% CI, 0.59-1.09]) and death (incidence rate, 4.6 versus 4.5 per 100 person-years; HR, 1.03 [95% CI, 0.82-1.29]). Rivaroxaban versus warfarin was associated with a higher risk of major bleeding (incidence rate, 4.9 versus 2.9 per 100 person-years; sub-HR, 1.65 [95% CI, 1.10-2.48]), with no difference in risks for stroke/systemic embolism and death. Apixaban versus rivaroxaban was associated with a lower risk of major bleeding (sub-HR, 0.53 [95% CI, 0.36-0.78]).
CONCLUSIONS: These real-world findings are consistent with potential safety advantages of apixaban over warfarin and rivaroxaban for patients with atrial fibrillation and severe chronic kidney disease. Further randomized trials comparing individual oral anticoagulants are warranted.

UNASSIGNED: The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE.
UNASSIGNED: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs.
UNASSIGNED: The analysis included 12 011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%].
UNASSIGNED: Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

UNASSIGNED: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.

BACKGROUND: Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin.
RESULTS: Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001).
CONCLUSIONS: Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.