Administration Of Direct Oral Anticoagulants Research Articles

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.

Venous thromboembolism secondary prophylaxis in elderly people (over 75-year-old) with low-dose direct oral anticoagulants: single-center Italian experience

Nowadays, direct oral anticoagulants (DOACs) represent the gold standard for venous thromboembolism (VTE) treatment and VTE secondary prophylaxis; nevertheless, the percentage of elderly patients in major trials and literature data about DOACs usage for VTE secondary prophylaxis in the elderly are scant. Our retrospective study tried to evaluate low-dose DOACs efficacy and safety for elderly VTE secondary prophylaxis in a real-life setting. A cohort of 73 patients (≥ 75 years) considered at high risk of VTE recurrence was treated with apixaban 2.5 mg twice daily (b.i.d.) or rivaroxaban 10 mg daily as VTE secondary prophylaxis. The median low-dose DOACs administration time was 18.40 months. Three (4.1%) VTE recurrence events were observed, with four bleeding events registered (5.5%), including one major bleeding (MB) (1.4%) and two clinically relevant non major bleeding (CRNMB) (2.7%). Our data suggest that low-dose DOACs may be effective and well tolerated for secondary VTE prophylaxis in elderly patients at high risk of VTE recurrence.

Post-extraction bleeding in patients on direct oral anticoagulants.

This study aimed to evaluate the association between use of direct oral anticoagulants (DOACs) and post-extraction bleeding and to quantify bleeding risk in patients receiving DOACs. The study included 293 patients who were taking DOACs and underwent tooth extraction (414 teeth). The patients were divided into those who had the extraction while taking DOACs and those who discontinued DOACs before the extraction. Bleeding complications were recorded and compared between the patient groups and types of DOACs. Of the 293 patients, 12 patients (6.9%) had post-extraction bleeding. Post-extraction bleeding occurred in 12 of the 414 tooth extraction sites. Among the 246 patients who underwent dental extraction while continuing DOAC therapy, 12 patients (8.5%) had post-extraction bleeding. Among the 47 patients who underwent dental extraction after discontinuing the administration of DOACs, none reported post-extraction bleeding. There was no significant difference in the number of patients with post-extraction bleeding between the two groups (P=0.122). Continuing DOAC therapy during dental extraction does not increase post-extraction bleeding tendency. These results are consistent with those of previous studies.

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.

Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban: A clinical prospective randomized study

BackgroundThe coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants has not been elucidated. ObjectiveOur aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. MethodsPatients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected 3 times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10–15 minutes after the start of vascular punctures. ResultsForty-two patients were enrolled. The prothrombin fragment 1+2 level, the primary end point, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median, 83 pmol/L; interquartile range, 56–133 pmol/L) than in the uninterrupted apixaban recipients (median, 1 pmol/L; interquartile range, −3 to 19 pmol/L; P < .001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. ConclusionUnlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

Heparin-Induced Thrombocytopenia (HIT) in the Direct Oral Anticoagulants (DOAC) Era

Heparin-induced thrombocytopenia (HIT) is an uncommon complication of heparin therapy with significant risk for severe morbidity and mortality. We investigated the role and outcome of direct oral anticoagulants (DOACs) for the management of HIT. After institutional review board (IRB) approval, a retrospective review was performed identifying all patients with positive HIT serotonin-release assays between 2020 and 2022 at two hospitals. The demographic and clinical variables were collected as follows: initial anticoagulant, dosing and indication, interval before onset of HIT, thrombotic complications, platelet nadir and recovery, direct thrombin inhibitor (DTI) and DOAC usage, and clinical outcomes. 15 patients were included in the study. 8 underwent a vascular procedure, 3 had cardiac surgery, 1 patient had both and was included in both groups, and 5 patients had either noncardiac, nonvascular surgery, or no surgery. 14 patients received unfractionated heparin (93% with therapeutic dosing), and 1 received prophylactic enoxaparin prior to diagnosis of HIT. The average time to diagnosis of HIT was 10.77days after initial anticoagulation. In-hospital mortality was 27%, related to Covid-19 infection (3/4) and intracranial hemorrhage (1/4). 40% developed thrombosis (67% venous, 33% arterial) after the diagnosis of HIT. 8/11 survivors were discharged on a DOAC. With DOAC therapy, platelet counts rebounded to an average of 265K (±104.6K) within an average of 2.3days and 364K (±273.9K) within 30days after initiation of a DOAC. No recurrent thrombosis occurred after DOAC administration and only one patient had persistent thrombocytopenia within 30days. Mortality and thrombosis (arterial and venous) are common complications in patients diagnosed with HIT. In patients who survive to discharge, DOACs are the most common discharge antithrombotic agent, with low rates of recurrent thrombosis and thrombocytopenia.

Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants.

Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105-0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157-10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin-bilirubin score (HR: 9.083, 95% CI: 1.118-73.76) was associated with bleeding events (p = 0.039). DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.

Risk factors for postgastric endoscopic submucosal dissection bleeding in direct oral anticoagulant users.

Bleeding after endoscopic submucosal dissection (ESD) for gastric tumors in patients taking antithrombotic drugs, in particular direct oral anticoagulants (DOACs), remains unresolved; therefore, we evaluated the risk factors for post-ESD bleeding and drug differences in patients taking DOACs. We included 278 patients taking antithrombotic drugs who underwent gastric ESD between January 2017 and March 2022. Antithrombotic drugs were withdrawn following the 2017 guidelines (Appendix on anticoagulants including DOACs). To further clarify differences in antithrombotic agents' effects, the peri-cancerous mucosa in the resected specimen was pathologically evaluated according to the Updated Sydney System. Multivariate analysis was performed to assess the risk of post-ESD bleeding. The incidence of post-ESD bleeding in patients taking DOACs was 19.6% (10/51). Among patients taking antithrombotic drugs, DOACs were identified as a possible factor involved in post-ESD bleeding (odds ratio [OR] 4.92). Among patients taking DOACs, possible factors included resection length diameter ≥30 mm (OR 3.72), presence of neutrophil infiltration (OR 2.71), lesions occurring in the lower third of stomach (OR 2.34), and preoperative antiplatelet use (OR 2.22). Post-ESD bleeding by DOAC type was 25.0% of patients (4/16) receiving apixaban, in 20.0% (3/15) receiving edoxaban, in 21.4% (3/14) receiving rivaroxaban, and in none of those receiving dabigatran. The administration of DOACs was shown to be a possible factor involved in post-ESD bleeding, and risk factors for patients taking DOACs included neutrophil infiltration. The pharmacological differences in the effects of DOACs contributing to bleeding in gastric ulcers suggest comparatively less bleeding with dabigatran after ESD.

Oral anticoagulants versus vitamin K antagonists in the treatment of non-valvular atrial fibrillation in patients with stage 4-5 chronic kidney disease

Aim. To compare the effectiveness and safety of direct oral anticoagulants (DOACs) with a vitamin K antagonist (VKA) in patients with atrial fibrillation (AF) and stage 4 and 5 chronic kidney disease (CKD).Material and methods. We searched in the PubMed, Google Scholar, and Web of Science databases from 1990 to 2022 for studies that compared DOACs with VKAs in patients with AF and stage 4 and 5 CKD. The patient, intervention, comparison, outcome (PICO) search strategy was used. Data were extracted by independent researchers and meta-analyzed.Results. A total of 6 studies were included in this meta-analysis. In terms of effectiveness, DOACs were comparable to VKAs. In terms of safety, DOACs and VKAs also had no statistical differences in hemorrhagic stroke, minor/gastrointestinal bleeding, overall mortality, but there was statistical significance in major bleeding. Conclusion. In terms of efficacy and safety, in general, DOACs were comparable to VKAs, but there were a number of following differences: the administration of DOACs to patients with stage 4 and 5 CKD, as well as those on hemodialysis, was accompanied by a significant reduction in the number of major bleedings, compared with warfarin therapy.

A real-world exploration into clinical outcomes of direct oral anticoagulant therapy in people with chronic kidney disease: a large hospital-based study

BackgroundThere is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap.MethodsAn anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis.ResultsFor both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10–2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79–0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14–0.58; p = 0.001), while the effect on ischaemic stroke was insignificant.ConclusionsA positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.Graphical

Secondary Prophylaxis of Venous Thromboembolism (VTE) with Low Dose Apixaban or Rivaroxaban: Results from a Patient Population with More than 2 Years of Median Follow-up.

Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Nowadays, DOACs represent the gold standard for long-term anticoagulation, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit low-intensity apixaban and rivaroxaban are approved for clinical usage as secondary VTE prophylaxis, there are few literature data regarding their efficacy and safety with a long follow-up. The aim of our study was to evaluate the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis in patients at high risk of VTE recurrence. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily with a follow-up ≥ 12 months. The examined patients were 323. The median low-dose DOAC administration time was 25.40 months (IQR 13.93-45.90). Twelve (3.7%) VTE recurrences were observed; 21 bleeding events were registered (6.5%), including one episode of Major bleeding (MB) (0.3%), 8 Clinically relevant nonmajor bleeding (CRNMB) (2.5%) and 12 minor bleeding (3.7%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between the rivaroxaban and apixaban groups. Patients included in the study for multiple episodes of VTE presented a significantly higher risk of a new VTE recurrence during low-intensity DOAC. Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis in patients at high risk of VTE recurrence; however, attention might be needed in their choice in such a scenario for patients who experienced multiple episodes of VTE.

Abstract WP144: Early Initiation of Anticoagulation is Safe After Ischemic Stroke With Atrial Fibrillation, Meta-Analysis and Systemic Review

Background: Large randomized clinical trials have established the superiority of Direct oral anticoagulants (DOACs) over Vitamin-K antagonists in atrial fibrillation (AF) related to Acute Ischemic stroke (AIS). However, the data regarding outcomes of early versus late administration of DOACs is limited, but few recent studies &amp; clinical trials provided some evidence. Methodology: The Preferred Reporting Items for Systematic Reviews &amp; Meta-Analyses (PRISMA) standards were followed for this systematic review &amp; meta-analysis". Our search strategy used the Population (AF-related AIS patients taking DOACs), Intervention (early anticoagulation; before 3-4 days), Comparison (late anticoagulation; after 3-4 days), Outcomes &amp; Study type (PICOS) question format. The outcomes of interest were Intracranial hemorrhage (ICH), ischemic stroke &amp; all-cause mortality. The data was pooled using Mantel-Haenszel random effect model &amp; the Higgins I 2 test was used to determine the heterogeneity in each analysis. Results: After the database search &amp; study screening, we included 3 prospective cohorts &amp; 1 RCT in our review. All four eligible studies were of good quality (the Newcastle Ottawa Scale &amp; Cochrane Risk of Bias tool 2). Of the 1831 patients who received DOACs in A-F related AIS, 966 were given before 3-4 days &amp; 865 people received them after 3-4 days. The adverse event of ICH (RR 0.65 [95% CI: 0.41 - 1.01] p = 0.68, I 2 = 0%) was similar in both early &amp; late groups. No significant difference in Risk of Ischemic stroke (RR 0.67 [95% CI: 0.36 - 1.24] p = 0.28, I 2 = 22%) &amp; all-cause mortality (RR 0.72 [95% CI: 0.45 - 1.17] p = 0.52, I 2 = 0%) was noted between the two groups. Conclusion: Our meta-analysis found that initiating DOACs within 3-4 days of AF-associated stroke is safe &amp; does not affect outcomes such as ICH incidence, stroke recurrence, or all-cause mortality.

Potential of Direct Oral Anticoagulant in Bleeding After Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis.

An increasing number of patients are undergoing gastric endoscopic submucosal dissection (ESD) with active prescriptions of direct oral anticoagulants (DOACs). Only a few reports have described the effects of DOAC intake on postoperative bleeding. We aimed to investigate the bleeding risk associated with DOACs after gastric ESD. Clinical studies published up to April 2022 showing bleeding rates after gastric ESD in patients taking DOACs were identified using electronic searches. The primary outcome was the rate of bleeding after gastric ESD in patients receiving DOACs compared to those not receiving antithrombotic therapy. In this meta-analysis, odds ratios (ORs) were calculated and pooled using a random effects model. The secondary outcome was the difference in the bleeding rate between patients treated with DOACs and those treated with warfarin and antiplatelet drugs. Seven studies were included in this meta-analysis. The pooled analysis showed that DOACs had a higher bleeding rate than non-thrombotic therapy (17.0% vs. 3.4%; OR 5.72; 95% confidence interval [CI], 4.33-7.54; I2 = 0%). The bleeding risk associated with DOAC administration was similar to that associated with warfarin (17.0% vs. 20.0%; OR 0.83; 95% CI 0.59-1.18; I2 = 0%), whereas it was higher than that associated with antiplatelet administration (16.9% vs. 11.0%; OR 1.63; 95% CI 1.14-2.34; I2 = 8%). This meta-analysis reveals that the bleeding risk of DOACs is higher than that of non-antithrombotics and antiplatelets, whereas it is comparable to that of warfarin. Gastric ESD in patients on anticoagulants requires careful postoperative management.

Clinical Benefits of Oral Anticoagulants for Elderly Patients With Cardioembolic Stroke at High Bleeding Risk.

The relationship between the severity of cardioembolic stroke (CES) and oral anticoagulant (OAC) treatment before stroke onset in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk remains unknown. A total of 364 consecutive patients (≥80 years) with CES and NVAF within 48 h following stroke onset were investigated. High bleeding risk was defined as follows: Bleeding history, renal dysfunction (creatinine clearance <30 ml/min), low body weight (≤45 kg), and antiplatelet or nonsteroidal anti-inflammatory drug use. Patients were divided into two groups: High bleeding risk (n=214) and non-high bleeding risk (n=150). We assessed stroke severity and functional outcome between the two groups, and evaluated the effect of therapy with direct OAC (DOAC) on stroke severity in the high-risk group. The high-risk group had a worse modified Rankin Scale (mRS) at discharge than the non-high-risk group [median: 4 (range=2-5) vs. 3 (range=1-4); p=0.02]. Patients in the high-risk group were categorized according to OAC treatment before stroke onset: No OAC (n=148), warfarin (n=46), and DOAC (n=20). The numbers of patients with National Institutes of Health Stroke Scale score (NIHSS) ≥8 on admission in these groups were 104 (70%), 30 (65%), and 8 (40%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR relative to no OAC=0.22, 95% confidence interval=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥4) at discharge (OR=0.31, 95% confidence interval=0.11-0.90; p=0.03). Very elderly patients with CES at high bleeding risk have unfavorable functional outcomes. DOAC administration may be associated with reduced stroke severity.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Recent Direct Oral Anticoagulant Use: A Systematic Review and Meta-Analysis.

Intravenous thrombolysis (IVT) is an effective stroke therapy that remains underused. Currently, the use of IVT in patients with recent direct oral anticoagulant (DOAC) intake is not recommended. In this study we aim to investigate the safety and efficacy of IVT in patients with acute ischemic stroke and recent DOAC use. A systematic review and meta-analysis of proportions evaluating IVT with recent DOAC use was conducted. Outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage, serious systemic bleeding, and 90-day functional independence (modified Rankin scale score 0-2). Additionally, rates were compared between patients receiving IVT using DOAC and non-DOAC by a random effect meta-analysis to calculate pooled odds ratios (OR) for each outcome. Finally, sensitivity analysis for idarucizumab, National Institutes of Health Stroke Scale, and timing of DOAC administration was completed. Fourteen studies with 247 079 patients were included (3610 in DOAC and 243 469 in non-DOAC). The rates of IVT complications in the DOAC group were 3% (95% CI, 3-4) symptomatic intracranial hemorrhage, 12% (95% CI, 7-19) any ICH, and 0.7% (95%CI, 0-1) serious systemic bleeding, and 90-day functional independence was achieved in 57% (95% CI, 43-70). The rates of symptomatic intracranial hemorrhage (3.4 versus 3.5%; OR, 0.95 [95% CI, 0.67-1.36]), any intracranial hemorrhage (17.7 versus 17.3%; OR, 1.23 [95% CI, 0.61-2.48]), serious systemic bleeding (0.7 versus 0.6%; OR, 1.27 [95% CI, 0.79-2.02]), and 90-day modified Rankin scale score 0-2 (46.4 versus 56.8%; OR, 1.21 [95% CI, 0.400-3.67]) did not differ between DOAC and non-DOAC groups. There was no difference in symptomatic intracranial hemorrhage rate based on idarucizumab administration. Patients with acute ischemic stroke treated with IVT in recent DOAC versus non-DOAC use have similar rates of hemorrhagic complications and functional independence. Further prospective randomized trials are warranted.

Oral Anticoagulant Therapy in Patients with Philadelphia-Negative Myeloproliferative Neoplasms: A Real-Life Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants

BACKGROUND Chronic myeloproliferative neoplasms (MPN) are characterized by an high risk of thrombosis and bleeding. Historically, vitamin K inhibitors (VKAs) have been the preferred oral anticoagulant therapy (OAT) for these patients (pts). However, nowadays, VKAs are being used less frequently, and direct oral anticoagulants (DOACs) are becoming more popular. Despite this trend, there is still limited evidence in the literature regarding the efficacy and safety of these drugs in the context of MPN. Specifically, there is a lack of data directly comparing VKAs and DOACs in a real-world clinical setting. AIMS The study aimed to conduct a real-world analysis comparing the efficacy and safety of DOACs and VKAs in patients with MPN. Both medications were prescribed for the treatment and secondary prevention of venous thromboembolism (VTE) or for the prevention of thrombosis in pts with atrial fibrillation (AF). The secondary endpoints were to assess the influence of common demographic, clinical, and hematological variables on the incidence of thrombotic events (TE) and bleeding events (BE) METHODS We conducted an observational retrospective monocentric study that enrolled all consecutive pts with MPN, followed at the MPN Clinic of the IRCCS Foundation S. Gerardo dei Tintori - Monza between 1993 and 2022, who received OAT with VKAs or DOACs for VTE or AF. For each pts, we collected demographic, clinical, biological, therapeutic, and hematological data. TE were categorized based on their type (arterial or venous) and location. BE were classified as minor, major, or clinically relevant non-major bleeding, according to the ISTH classification. Thrombosis-free survival (TFS) and bleeding-free survival (BFS) were assessed from the initiation of OAT until the occurrence of the first TE or BE, respectively, and estimated using Kaplan-Meier analysis. The other analyses were conducted using common statistical methods. Multivariable analyses included previously established risk factors for BE and TE. RESULTS A total of 156 pts were enrolled: 89 were women (57%). The median age was 69 years (range 25-92); 61 were affected by myelofibrosis, 35 by polycythemia vera, and 48 by essential thrombocythemia. 64 pts received OAT with VKAs (41%), and 92 with DOACs (59%). For 82 pts OAT was prescribed for AF (52.6%), and for 74 for VTE (47.4%). 17 pts treated with DOACs for VTE received a reduced-dose extended treatment (45.9%). The median exposure time to OAT was 5.8 years in the VKAs group (range 0.2-20 years) and 1.77 years in the DOACs group (range 0.2-10 years). After a median follow-up of 3,2 years, 14 TE were reported: 5 (35.7%) in the DOAC-treated group, of which 4 were arterial (80%), and 9 (64.3%) in the VKA-treated group (7 arterial - 77.8%). The incidence rate of TE was 2.11 thrombosis/pts/year in the VKAs group and 2.14 thrombosis/pts/year in the DOACs group. There were no significant differences in terms of TFS between the two groups, whether considering the entire population or analyzing the therapeutic indications separately (respectively p=0.72, p=0.53, p=0.55). Overall, there were 27 BE: 13 in the DOACs group (51.9%), 14 in the VKAs group (48.1%). Among these, we report 8 major BE, 4 in both groups. The incidence rate of BE was 5.6/pts/year in the DOACs group and 3.3/pts/year in the VKAs group. We did not observe significant differences in terms of BFS analyzing the whole population and the VTE group (respectively p=0.13 and p=0.75), while we found a trend for lower BFS in pts treated with DOACs for AF (p=0.08, Fig. 1). In a multivariate model, adjusted for time of exposition to OAT, age, gender and antiplatelet treatment, the risk of BE was associated solely with DOACs administration (hazard ratio 3.7, p=0.01) We found no significant differences in the risk of TE and BE when considering the various types of DOACs used. Moreover, 45 (28.8%) patients received concomitant antiplatelet therapy, and we found no significant differences in the risk of BE or TE compared to the other group (p=0.39 and p=0.41, respectively). CONCLUSIONS To our knowledge, this is the largest study investigating the safety and efficacy of DOACs compared to VKAs for the treatment and prevention of TE in pts with MPN and VTE or AF. Our findings suggest that DOACs are as effective as VKAs, but they appear to exhibit a trend towards a higher overall risk of BE, especially in the AF group. More data from prospective multicentric studies are necessary to validate our results.

Inhospital outcomes of myocardial infarction in patients receiving direct oral anticoagulants

Aim. To evaluate the clinical course and inhospital outcomes of myocardial infarction (MI) in patients receiving continuous direct oral anticoagulant (DOAC) therapy.Material and methods. Data from 390 patients treated for MI were included in the analysis. The mean age was 64.1±12.8 years. The majority were men (61,5%; n=240). All patients underwent standard diagnostic and therapeutic procedures according to clinical guidelines, including coronary angiography and percutaneous coronary intervention when indicated. Clinical, anamnestic and laboratory data (including C-reactive protein level, troponin I, coagulation test) were analysed. The inhospital course of MI, mortality and incidence of complications were evaluated.Results. Patients were divided into two groups according to DOAC therapy received. The main group included 41 patients with constant DOAC intake, while the control group consisted of 349 patients not receiving DOAC. Patients aged 65 years and older accounted for 68,3% (n=28) of the main group (p=0,0033), with a high proportion of cerebral circulation disorders and venous thrombosis (p&lt;0,01). Atrial fibrillation was diagnosed in 75,6% (n=31) of patients in the main group (p&lt;0,0001). ST elevation MI (STEMI) was seen in 39,0% (n=16) of cases in the main group and 47,3% (n=165) of cases in the control group (p=0,3161). As a result, 85,4% (n=35) of patients in the main group had a high GRACE-1 risk, compared to 50,4% (n=176) in the control group (p&lt;0,0001). The two groups did not differ significantly in the severity of heart failure (p=0,1549). ST-segment resolution on admission electrocardiogram was observed in 43,8% (n=7) of the main group and 18,1% (n=30) of the control group (p=0,0238). According to coronary involvement severity and the type of antegrade flow in the infarct-related artery, patients in both groups were comparable (p&gt;0,05). Prior DOAC administration had no significant effect on the incidence of gastrointestinal bleeding (odds ratio (OR), 3,96 (95% Confidence Interval (CI) 0,76–20,66)) and mortality (OR 1,47 (95% CI 0,37-5,85)) during hospitalization.Conclusion. Patients with MI who received continuous DOAC therapy had significantly more frequent ST-segment resolution at hospital admission compared with patients who did not receive DOAC. DOAC administration had no significant effect on mortality and incidence of inhospital complications of MI.

Comparison of Khorana Vs. Onkotev Predictive Score to Individualize Anticoagulant Prophylaxis in Ambulatory Patients with Cancer

Background: The current guidelines [ J Clin Oncol. 2020;38(5):496] recommend using the risk assessment model (RAM) Khorana score ≥2 [ Blood. 2008;111(10):4902-4907] for primary anticoagulant prophylaxis (PP) of venous thromboembolism (VTE) in patients treated for cancer in an outpatient setting. Recently, a novel RAM, the ONKOTEV score [ JAMA Network Open 2023;6(2):e230010] has been prospectively externally validated with good predictive performance. Like all other established RAMs, the Khorana Score and ONKOTEV models aim to assess the incidence of VTE accurately but do not integrate the expected benefits and potential harms of treatment to determine the clinical utility of the competing management alternatives. We set out to compare the clinical utility of the Khorana Score vs. the ONKOTEV predictive model to guide the PP of VTE in patients receiving anticancer treatment. Methods: We used the ONKOTEV validation dataset (n=425). The ONKOTEV score included the Khorana Score (dichotomized as Khorana score &amp;gt;2 vs. ≤ 2) and three readily available clinical information (also dichotomized): history of previous VTE, the presence of metastatic disease, and clinical or radiological assessment of vascular or lymphatic compression by tumor. After assessing the models' performance (discrimination, calibration), we applied a generalized decision curve analysis (gDCA) to integrate the effects of treatments with the models' predictive accuracy. This, in turn, allowed us to develop individualized recommendations for using PP for VTE in patients receiving anticancer treatment. We calculated net benefits (NB) to compare three management strategies: don't provide any treatment vs. administer prophylaxis to all patients receiving anticancer treatment for VTE vs. use the Khorana or ONKOTEV model to guide PP of VTE. According to gDCA, the best treatment is the one with the highest NB. We obtained data on treatment effects from the meta-analysis of published randomized trials comparing direct oral anticoagulants (DOAC) and low-molecular-weight heparins (LMWH) vs. placebo [ Annals of Palliative Medicine. 2020;9(5):2970]. We estimated that DOAC reduced the risk of VTE by 57% [relative risk reduction (RRR) =0.57 (95%CI: 0.13 to 0.79)] and LMWH by 48% [RRR=0.48 (95%CI: 0.42 to 0.66)]. We assessed the major bleeding rate on DOAC as 0.01 (95%CI: 0.006 to 0.04) and 0.02 (95%CI: 0.01 to 0.03) for LMWH. Results: Both RAMs had a satisfactory performance. Harell's C discrimination statistics was 0.71 for ONKOTEV and 0.66 for Khorana Score with good calibration properties (with intercept and the slope not statistically significantly different from 0 and 1, respectively). Fig 1A shows the results based on the default assumptions: if the patient values avoiding the morbidity of VTE 1.6 to 5 times more (0.2&amp;lt;RV&amp;lt;0.6) than the major bleeding, then offering DOAC to all patients receiving PP for VTE represents the most optimal management strategy. When the patients would rather avoid the consequences of the major bleeding by &amp;gt;2.5x more than the morbidity of VTE, using the ONKOTEV model to guide the administration of DOAC represents the best treatment strategy. If we assume that RRR ≤ 0.2, relying on the ONKOTEV model to guide the use of DOAC becomes the most optimal approach to PP of VTE in patients receiving anticancer treatment (Fig 1B). Conclusion: ONKOTEV model is superior to Khorana Score in guiding individualized PP for VTE in ambulatory patients with cancer. It is particularly helpful when the patient values avoiding major bleeding more than the morbidity of VTE. Our analysis provides new recommendations for PP of VTE receiving outpatient treatment for cancer, calling for updating the current guidelines for PP of VTE in this setting.

Co-administered oral anticoagulants with nonsteroidal anti-inflammatory drugs and the risk of bleeding: A systematic review and meta-analysis

BackgroundThe bleeding risk of individuals taking nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly with oral anticoagulants (OACs) compared to OACs alone remains controversial. This meta-analysis aims to evaluate the bleeding risk of concomitant use of OACs and NSAIDs, and to make comparisons between different OACs types. MethodsPubMed, Embase, Cochrane Library and Web of Science were searched systematically until 11 August 2023 for studies reporting the bleeding risk of combined use of OACs and NSAIDs. Summary estimates with 95 % confidence interval (CI) were calculated by meta-analysis. Heterogeneity was assessed by I2 statistics. We performed subgroup analyses according to the types of NSAIDs, the types of OACs, the indication for therapy and the types of research. ResultsA total of 27 studies were included. Taking vitamin K antagonist (VKAs) concurrently with NSAIDs was associated with a higher risk of any bleeding [odds ratio (OR) = 1.55; 95 % CI, 1.21 to 2.00; P = 0.0007), gastrointestinal bleeding (OR = 2.66; 95 % CI, 1.96 to 3.62; P < 0.00001) as well as major bleeding (OR = 1.55; 95 % CI, 1.04 to 2.30; P = 0.03). Concomitant exposure to direct OACs (DOACs) and NSAIDs increased the risks of any bleeding (OR = 1.54; 95 % CI, 1.33 to 1.80; P < 0.00001) and gastrointestinal bleeding (OR = 2.18; 95 % CI, 1.02 to 4.69; P = 0.05), but was nonsignificant for major bleeding (OR = 1.42; 95 % CI, 0.84 to 2.40; P = 0.19). Without considering other confounding factors, concomitant exposure to DOACs and NSAIDs was associated with a lower risk of bleeding compared to VKAs plus NSAIDs (OR = 0.55; 95 % CI, 0.34 to 0.90; P = 0.02) in atrial fibrillation and venous thromboembolism patients. Subgroup analyses showed that compared to VKAs only, concurrent administration of VKAs and nonselective NSAIDs was associated with a heightened risk of bleeding (OR = 3.06; 95%CI, 1.99 to 4.71; P < 0.00001). However, inconsistent result was observed when it comes to selective NSAIDs (OR = 1.99; 95%CI, 0.87 to 4.51; P = 0.10). Compared to DOACs only, combined use of rivaroxaban and NSAIDs increased bleeding risk (OR = 1.61; 95 % CI, 1.21 to 2.14; P = 0.001), while dabigatran co-administered with NSAIDs showed no significant association with bleeding (OR = 1.40; 95 % CI, 0.80 to 2.44; P = 0.24). Regardless of indication, concomitant administration of NSAIDs and DOACs increased the risk of bleeding. ConclusionsCo-administered OACs with NSAIDs significantly increased the risk of any bleeding and gastrointestinal bleeding compared to OACs alone. Without considering other confounding factors, DOACs were associated with a lower risk of bleeding compared to VKAs in atrial fibrillation and venous thromboembolism patients.

Thromboembolic complications during and after embolization of unruptured aneurysms: A chronological outcome in periprocedural thromboembolic events.

Ischemic complications develop after elective coil embolization procedures at a certain rate. The prevention of these events has been a longstanding issue for many interventional neuroradiologists. This study aimed to clarify whether procedural ischemic events after unruptured aneurysm embolization decrease over time with perioperative anti-thromboembolic treatment or surgical experience. This study included patients with cerebral aneurysms in our institution between July 2012 and June 2020. Dual-antiplatelet therapy (DAPT) was performed (Phase 1). Thromboembolic events developed at a certain rate; thus, rivaroxaban was administered with single-antiplatelet therapy (SAPT) to improve thromboembolic results (Phase 2), showing better outcomes than in Phase 1. Subsequently, DAPT was administered again (Phase 3). Ischemic complications were evaluated in each phase or compared between the DAPT group and the direct oral anticoagulant (DOAC) with the clopidogrel (DOAC+SAPT) group. Relatively, fewer symptomatic ischemic events were noted in Phase 2 or the DOAC+SAPT group, but the outcome was not better in Phase 3 than in Phase 2. Symptomatic complications were more common in Phase 3 than in Phases 1 and 2. Ischemic complications occurred at a certain rate after endovascular procedures for unruptured aneurysms. The incidence did not decrease over time; particularly, standard DAPT plus postoperative anti-thromboembolic medication did not adequately decrease complications in Phase 3 compared to Phases 1 and 2. Therefore, accumulated experience or a learning curve could not explain the results. DOAC administration might decrease the risk of these events, but further accumulation of evidence or prospective investigation is warranted.