Effect of different anticoagulants and antiplatelets on intraoral bleeding time during professional oral hygiene session.

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. MATERIALS AND 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. CLINICAL SIGNIFICANCE: 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.

Effectiveness and Safety of Extended Treatment Apixaban Versus Low-Molecular-Weight Heparin in Cancer-Associated Venous Thromboembolism.

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.

Factor Xa Inhibitors Versus Vitamin K Antagonists in Atrial Fibrillation Patients with End-Stage Kidney Disease on Dialysis: A Meta-Analysis.

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. CONCLUSION: 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.

Risk of Major Bleeding, Stroke/Systemic Embolism, and Death Associated With Different Oral Anticoagulants in Patients With Atrial Fibrillation and Severe Chronic Kidney Disease.

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. METHODS AND 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.

Prognosis of Patients With Ischemic Stroke With Prior Anticoagulant Therapy: Direct Oral Anticoagulants Versus Warfarin.

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. METHODS AND 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.

A pilot study of safety and efficacy comparison of low molecular heparin calcium sequential oral anticoagulants in the treatment of cirrhotic portal vein thrombosis.

BACKGROUND: The objective of this study is to compare and assess the efficacy and safety of low-molecular-weight heparin calcium (LMWH-Ca), followed by either warfarin or rivaroxaban, as treatment options for portal vein thrombosis (PVT) in patients with cirrhosis. METHODS: In this pilot study, cirrhotic (with liver function score of Child-Pugh A) patients diagnosed with PVT who were not on anticoagulant therapy received 2 weeks of subcutaneous injections of LMWH-Ca. They were then randomized to either warfarin (a full course of oral warfarin for 6 months) or rivaroxaban (a full course of oral rivaroxaban for 2 months), with 30 cases in each group. After a treatment period of up to 6 months, a comparative analysis was performed to assess the efficacy and safety of both groups. Volumetric changes in PVT were monitored dynamically using enhanced computed tomography scans before treatment at week 2 and month 6. RESULTS: There were no statistically significant differences in the clinical characteristics of the patients between the two groups. Rivaroxaban treatment reduced PVT median volume from 1.83 cm3 at week 2 to 0.0 cm3 at month 6 and prevented the worsening of PVT after 6 months of treatment with LMWH-Ca (P < 0.001). On the other hand, warfarin treatment increased PVT median volume from 1.95 cm3 at week 2 to 3.78 cm3 at month 6 (P = 0.002). None of the 30 patients in the rivaroxaban group had clinically significant gastrointestinal bleeding, while 2 of the 30 patients (7%) in the warfarin group had gastrointestinal bleeding (P = 0.317). CONCLUSION: Rivaroxaban followed by LMWH-Ca is an effective anticoagulant treatment strategy for PVT in cirrhosis.

Apixaban vs Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights From ARTESiA.

BACKGROUND: ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation) demonstrated that apixaban, compared with aspirin, significantly reduced stroke and systemic embolism (SE) but increased major bleeding in patients with subclinical atrial fibrillation. OBJECTIVES: To help inform decision making, the authors evaluated the efficacy and safety of apixaban according to baseline CHA2DS2-VASc score. METHODS: We performed a subgroup analysis according to baseline CHA2DS2-VASc score and assessed both the relative and absolute differences in stroke/SE and major bleeding. RESULTS: Baseline CHA2DS2-VASc scores were <4 in 1,578 (39.4%) patients, 4 in 1,349 (33.6%), and >4 in 1,085 (27.0%). For patients with CHA2DS2-VASc >4, the rate of stroke was 0.98%/year with apixaban and 2.25%/year with aspirin; compared with aspirin, apixaban prevented 1.28 (95% CI: 0.43-2.12) strokes/SE per 100 patient-years and caused 0.68 (95% CI: -0.23 to 1.57) major bleeds. For CHA2DS2-VASc <4, the stroke/SE rate was 0.85%/year with apixaban and 0.97%/year with aspirin. Apixaban prevented 0.12 (95% CI: -0.38 to 0.62) strokes/SE per 100 patient-years and caused 0.33 (95% CI: -0.27 to 0.92) major bleeds. For patients with CHA2DS2-VASc =4, apixaban prevented 0.32 (95% CI: -0.16 to 0.79) strokes/SE per 100 patient-years and caused 0.28 (95% CI: -0.30 to 0.86) major bleeds. CONCLUSIONS: One in 4 patients in ARTESiA with subclinical atrial fibrillation had a CHA2DS2-VASc score >4 and a stroke/SE risk of 2.2% per year. For these patients, the benefits of treatment with apixaban in preventing stroke/SE are greater than the risks. The opposite is true for patients with CHA2DS2-VASc score <4. A substantial intermediate group (CHA2DS2-VASc =4) exists in which patient preferences will inform treatment decisions. (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; NCT01938248).

Comparison of warfarin, rivaroxaban, and dabigatran for effectiveness and safety in atrial fibrillation patients with different CHA2DS2-VASc scores: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aims to compare the effectiveness and safety of warfarin, rivaroxaban, and dabigatran in atrial fibrillation (AF) patients with different CHA2DS2-VASc scores in northern China. METHODS: A retrospective cohort study was performed to evaluate anticoagulation in AF patients at the second affiliated hospital of Harbin Medical University from September 2018 to August 2019. Patients included in this study (n = 806) received warfarin (n = 300), or rivaroxaban (n = 203), or dabigatran (n = 303). Baseline characteristics and follow-up data including adherence, bleeding events and ischemic stroke (IS) events were collected. RESULTS: Patients receiving rivaroxaban (73.9%) or dabigatran (73.6%) showed better adherence than those receiving warfarin (56.7%). Compared with warfarin-treated patients, dabigatran-treated patients had lower incidence of bleeding events (10.9% vs 19.3%, χ2 = 8.385, P = 0.004) and rivaroxaban-treated patients had lower incidence of major adverse cardiovascular events (7.4% vs 13.7%, χ2 = 4.822, P = 0.028). We classified patients into three groups based on CHA2DS2-VASc score (0-1, 2-3, ≥ 4). In dabigatran intervention, incidence of bleeding events was higher in patients with score 0-1 (20.0%) than those with score 2-3 (7.9%, χ2 = 5.772, P = 0.016) or score ≥ 4 (8.6%, χ2 = 4.682, P = 0.030). Patients with score 0-1 in warfarin or rivaroxaban therapy had a similar but not significant increase of bleeding compared with patients with score 2-3 or score ≥ 4, respectively. During the follow-up, 33 of 806 patients experienced IS and more than half (19, 57.6%) were patients with score ≥ 4. Comparing patients with score 0-1 and 2-3, the latter had an significant reduction of IS in patients prescribed warfarin and non-significant reduction in rivaroxaban and dabigatran therapy. CONCLUSION: Compared with warfarin therapy, patients with different CHA2DS2-VASc scores receiving either rivaroxaban or dabigatran were associated with higher persistence. AF patients with score ≥ 4 were more likely to experience IS events while hemorrhagic tendency preferred patients with low score 0-1.

Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

BACKGROUND: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events. METHODS: A systematic review and meta-analysis was performed. RESULTS: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%). CONCLUSION: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

In device-detected AF, DOACs vs. aspirin or placebo reduce ischemic stroke and increase major bleeding.

SOURCE CITATION: McIntyre WF, Benz AP, Becher N, et al. Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: a study-level meta-analysis of the NOAH-AFNET 6 and ARTESiA trials. Circulation. 2024;149:981-988. 37952187.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

'X' marks the spot! Utilising factor Xa inhibitors to optimise thromboprophylaxis in multiple myeloma.

Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality among multiple myeloma patients. Chang and colleagues' findings indicate that factor Xa inhibitors are as effective as warfarin in preventing VTE without raising the risk of gastrointestinal or intracranial bleeding complications. Commentary on: Chang et al. The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy. Br J Haematol 2024;205:473-477.