Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare.

INTRODUCTION: Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. METHODS: Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). CONCLUSION: NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.

[Anticoagulant therapy in venous thromboembolism and bleeding risk: focus on the use of predictive scores.] / Terapia anticoagulante nel tromboembolismo venoso e rischio emorragico: focus sull'utilizzo di score predittivi.

The standard treatment for venous thromboembolism (Vte) is anticoagulation. Drug selection and treatment duration will depend on the clinical presentation, the existence of provoking factors, bleeding risk, and the patient's preferences. Anticoagulation therapy is indicated for 3-6 months in all patients with acute Vte but may be extended, even indefinitely in some cases. The most severe side effect of anticoagulation is bleeding, with the highest risk occurring during the 1st months of therapy. Balancing the risk of bleeding and the risk of recurrence in patients with Vte remain a major issue. There are, currently, no simple and validated predictive scores to estimate the long-term bleeding risk in patients undergoing anticoagulant treatment and to safely select those patients with higher bleeding risk. In this review we will examine some of these scores, including the RIETE scores, the HAS-BLED SCORE, the VTE-BLEED score, the VTE- PREDICT and the ACCP guidelines and the timing for their application in the patient's population treated for Vte as well as the initial and long-term management and evaluation of thromboembolic disease.

Catheter and Non-Catheter-Related Venous Thromboembolism in Cancer Patients: Survival, Anticoagulation Efficacy, and Safety.

PURPOSE: To investigate the differences in survival after venous thromboembolism (VTE) and anticoagulation efficacy and safety between catheter (CRVTE) and non-catheter-related VTE (NCRVTE) in cancer patients. METHODS: A retrospective research was conducted, and consecutive cancer (digestive, respiratory, genitourinary, blood and lymphatic, and the other cancers) patients with VTE were enrolled. The anticoagulation therapies included low-molecular-weight heparin (LMWH), warfarin, new type of direct oral anticoagulants (NDOACs), LMWH combined with warfarin, and LMWH combined with NDOACs. Data were collected from the electronic medical record database of our hospital and were analyzed accordingly by Kruskal-Wallis H Test, Chi-square test, Fisher's exact test, Logistic regressions, Kaplan-Meier analysis, and Cox regressions. RESULTS: 263 patients were included, median age in years (interquartile range) was 64(56-71) and 60.5% were male. VTE recurrence rate was 16.7% in CRVTE group which was significantly lower than 34.8% in NCRVTE group (P = .032). Heart diseases were independently associated with VTE recurrence (P = .025). Kaplan-Meier survival estimates at 1, 2, and 3 years for CRVTE group were 62.5%, 60.0%, and 47.5%, respectively, compared with 47.9% (P = .130), 38.7% (P = .028), and 30.1% (P = .046), respectively, for NCRVTE group. Cox regression showed surgery (P = .003), anticoagulation therapy types (P = .009), VTE types (P = .006) and cancer types (P = .039) were independent prognostic factors for 3-year survival after VTE. Nonmajor and major bleeding were not significantly different (P = .417). Anticoagulation therapy types were independently associated with the bleeding events (P = .030). CONCLUSIONS: Cancer patients with CRVTE potentially have a better anticoagulation efficacy and survival compared to NCRVTE, and the anticoagulation safety seems no significant difference.

Thromboprophylaxis in oesophageal cancer patients-a study protocol for a randomised, controlled trial (TOP-RCT).

BACKGROUND: The purpose of the study is to examine if prolonged thromboprophylaxis decreases the risk of thrombosis after intended curative surgery for oesophageal cancer. Study results are expected to inform a guideline for thromboprophylaxis after oesophageal cancer surgery. The perspective is to reduce morbidity and mortality in this critically ill patient group. Thrombosis is the second-most common cause of cancer death after the cancer itself. The risk of thrombosis depends on the cancer type, and upper gastrointestinal cancers are considered high risk. This risk is further increased when patients undergo surgery. However, only few studies have investigated the peri- and postoperative coagulation profile in oesophageal cancer patients. Due to this lack of knowledge, prophylaxis is currently restricted to 5000 IU (international units) low-molecular weight heparin daily from surgery until discharge from hospital (approximately 10 days), whereas patients with gastric cancer receive 30 days of treatment. The present study examines whether a 30-day treatment is superior and safe, compared with the current standard treatment. METHODS: The study is a randomised controlled trial. Inclusion is ongoing, and we aim to include 100 patients. Blood samples are drawn before and after surgery, and the coagulation is extensively examined. The primary endpoint is the difference in plasma levels of prothrombin fragment 1 + 2 (F1 + 2) 30 days after surgery between the intervention and the standard group. Furthermore, patients are examined with ultrasound to screen for asymptomatic venous thrombotic events (VTE). Secondary endpoints are incidence of bleeding, symptomatic and asymptomatic VTE and mortality 30 days 1 one year after surgery. DISCUSSION: The study will provide valuable information on the perioperative coagulation profile and VTE risk of oesophageal cancer patients. The study seeks to aid in optimising the postoperative thromboprophylaxis, and the perspective is to reduce morbidity and mortality in this at-risk patient population. TRIALS REGISTRATION: The trial was prospectively registered at the EU Clinical Trials Register with ID 2021-001335-24 on 30 June 2021 and at ClinicalTrials.gov with study identifier NCT05067153.

Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

BACKGROUND: The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. METHODS: This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. RESULTS: The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. CONCLUSION: Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs.

[Pulmonary embolism: outpatient treatment and follow-up]. / Lungenembolie: ambulante Therapie und Nachsorge.

Despite declining numbers - older people in particular - often die from pulmonary embolism. A rapid assessment of the risk in the event of a suspected embolism, the exclusion of comorbidities and the appropriate therapy are the focus of the current guidelines. Early and subsequent outpatient treatment of a patient with acute PE generally requires 3 criteria: low risk of early complications, the absence of serious comorbidities and the highest possible safety at home and, in the event of a complication, rapid access to acute care in the hospital. For patients with a high risk of VTE recurrence, the long-term dosage of secondary drug prophylaxis is not yet clear - studies are currently underway. In patients at moderate risk of VTE recurrence, low-dose secondary prophylaxis can be used to reduce the risk of bleeding. Outpatient pulmonary embolism follow-up care is becoming increasingly important, because studies have shown several times that serious long-term consequences can occur. In pulmonary embolism patients with persistent dyspnea, reduced performance or risk of CTEPH, an outpatient evaluation of the right ventricle using echocardiography, if necessary, in combination with the determination of natriuretic peptides or spiroergometry, is recommended.

[Women-specific aspects of venous thromboembolism]. / Frauenspezifische Aspekte bei venöser Thromboembolie.

Women have a higher lifetime risk of venous thromboembolism (VTE) than men. Hormone-associated risk factors such as pregnancy, contraception and hormone replacement therapy contribute significantly to this. Contraception with combined hormonal contraception increases the risk of VTE in young women, with the extent of the increase in risk being determined by the level of the estrogen dose and the progestin component. After hormone associated VTE, temporary anticoagulation is sufficient in many cases, provided there are no additional persistent risk factors. Affected women should be informed that the risk of VTE recurrence is increased in a subsequent pregnancy and usually requires VTE prophylaxis with low molecular weight heparin during pregnancy. If the suspicion of recurrent VTE arises during pregnancy, diagnostics must be carried out promptly so that deep vein thrombosis and/or pulmonary embolism can be reliably confirmed or ruled out.

[Environmental diagnostics for venous thromboembolism - thrombophilia and tumor screening]. / Umfelddiagnostik bei venöser Thromboembolie ­ Thrombophilie- und Tumor-Screening.

Inadequate treatment of venous thromboembolism can have fatal consequences that are often irreversible. If the indication is given, long-term therapeutic anticoagulation may be necessary to reduce the risk of recurrence for those affected. On the other hand, there is an increased risk of bleeding due to continued anticoagulation, so an individual risk/benefit assessment is necessary. A careful assessment of possible contributing factors is therefore essential. If uncertainty persists, comprehensive environmental diagnostics with regard to thrombophilia or cancer can be helpful.

Relationship between body mass index and clinical events in patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: It is still unclear whether body mass index (BMI) affects bleeding and cardiovascular events in patients requiring oral anticoagulants (OAC) for atrial fibrillation (AF) and antiplatelet agents after percutaneous coronary intervention (PCI) for coronary artery disease (CAD). The aim of this study was to evaluate the relationship between BMI and clinical events in patients who underwent PCI under OAC therapy for AF. METHOD: This was a multicenter, observational cohort study conducted at 15 institutions in Japan. AF patients who underwent PCI with drug-eluting stents for CAD were retrospectively and prospectively included. Patients were divided into the Group 1 (BMI <21.3 kg/m2) and the Group 2 (BMI ≥21.3 kg/m2) according to the first-quartile value of BMI. The primary endpoint was net adverse clinical events (NACE), a composite of major adverse cardiovascular events (MACE) and major bleeding events within one year after index PCI procedure. RESULTS: In the 720 patients, 180 patients (25.0%) had BMI value <21.3 kg/m2. While the rates of NACE and MACE were significantly higher in the Group 1 than the counterpart (21.1% vs. 11.9%, p = 0.003 and 17.2% vs. 8.9%, p = 0.004), that of major bleeding did not differ significantly between the 2 groups (5.6% vs. 4.3%, p = 0.54). The cumulative rate of NACE and MACE was significantly higher in the Group 1 than the Group 2 (both log-rank p = 0.002), although that of major bleeding events was equivalent between the 2 groups (log-rank p = 0.41). In multivariable Cox regression analyses, while BMI value <21.3 kg/m2 was not associated with major bleeding events, that cut-off value was an independent predictor for increased NACE and MACE. CONCLUSIONS: Among the patients undergoing PCI for CAD and requiring OAC for AF, BMI value was a useful indicator to predict major adverse clinical events.

Risks of oral anticoagulants: Analysis of adverse drug reactions reported to the Portuguese National Pharmacovigilance System.

Cardiovascular diseases are the leading cause of death globally, making the use of oral anticoagulants for prevention increasingly important. Historically, warfarin has played a significant role in this context. In recent years, introduction of new oral anticoagulants, such as rivaroxaban, apixaban, dabigatran, and edoxaban, has been seen. This study evaluates the risk associated with the use of oral anticoagulants by analyzing spontaneous adverse drug reactions reported to the Portuguese Pharmacovigilance System from 2012 to 2021. The study includes 951 adverse drug reactions reports, with the majority (n = 770; 80.97%) classified as serious. Of the 770 serious adverse drug reactions reports, the most commonly reported seriousness criterion was "Clinically Important" (n = 350; 45.45%). In terms of demographics, there was a higher reporting rate among the elderly population, with a greater prevalence of females. The System Organ Class group with the highest number of adverse drug reactions was "Gastrointestinal disorders," with the most commonly reported Preferred Term being "Gastrointestinal hemorrhage," and dabigatran was the most frequently reported drug. In summary, oral anticoagulants have adverse drug reactions that require continuous monitoring. Accurate identification and monitorization of adverse drug reactions is an important starting point to improve drug safety in population.

International Digestive Endoscopy Network Consensus on the Management of Antithrombotic Agents in Patients Undergoing Gastrointestinal Endoscopy.

Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

[Diagnostics and treatment of pulmonary artery embolisms]. / Diagnostik und Therapie der Lungenarterienembolie.

In recent years the diagnostics of pulmonary artery embolisms (PE) has gained significance, with confirmation occurring in only about 15-25 % of suspected cases. Despite technological advances, radiological methods remain problematic due to radiation and contrast medium exposure. Clinical scores play a crucial role in the risk assessment of PE. High-risk situations call for specific measures, while negative D­dimers can help avoid overdiagnosis. Computed tomographic pulmonary angiography (CTPA) remains the gold standard with high sensitivity and specificity. Treatment requires an interdisciplinary team (pulmonary embolism response team, PERT). Anticoagulation is an option for stable patients, while in unstable or unsuccessful courses, thrombolysis or interventional procedures can be considered. Side effects, especially the risk of bleeding, need to be considered for both forms of treatment.

Effectiveness and safety of low molecular weight heparin in the management of acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that low-molecular-weight heparin (LMWH) may play a role in mitigating the severity of acute pancreatitis (AP). This systematic review and meta-analysis aims to synthesise existing evidence on the effectiveness and safety of LMWH in the treatment of moderately-severe and severe AP. METHODS: This systematic review and meta-analysis was conducted in accordance with the 2020 update of the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The systematic search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, Scopus, and EMBASE, covering studies published up to February 2024. Randomised controlled trials (RCTs) and observational studies (n-RCTs) that reported the differences in the outcomes of AP for patients receiving LMWH in addition to the standard treatment (Intervention), compared to patients managed by standard treatment without LMWH (Control) were eligible. A random-effects model was used to calculate the pooled relative risk (RR) and mean differences (MD) with the corresponding 95% CI. RESULTS: Thirteen studies were included in the meta-analysis, all published between 2004 and 2022. Eight studies were RCTs, and five were n-RCTs. Data from 13,709 patients (6.971 Interventions and 6.738 Controls) were analysed. The comparison of Intervention and Control groups showed the superiority of LMWH to standard treatments in terms of overall mortality (RR = 0.44, 95% CI = 0.31; 0.64, P < 0.0001, I2 = 51%), acute necrotic collections (RR = 0.24, 95% CI = 0.09; 0.62, P = 0.003, I2 = 0%), and organ failure (RR = 0.67, 95% CI = 0.48; 0.93, P = 0.02, I2 = 78%). The Intervention group showed superior outcomes compared with the Control group for gastrointestinal bleeding (RR = 0.64, 95% CI = 0.44; 0.94, P = 0.02, I2 = 0%), length of hospital stay (MD= - 6.08, 95% CI = - 10.08; - 2.07, P = 0.003, I2 = 98%), need for operative interventions (RR = 0.50, 95% CI = 0.29; 0.87, P = 0.01, I2 = 61%), and vascular thrombosis (RR = 0.43, 95% CI = 0.31; 0.61, P < 0.00001, I2 = 0%). CONCLUSIONS: Moderate to high-quality evidence suggests that early intervention with LMWH could improve the prognosis of non-mild AP in terms of mortality, organ failure, and decreased incidence of vascular thrombosis. In light of our findings, integrating LMWH into the treatment regimen for moderate-severe to severe AP is advocated.

Unresolved questions on venous thromboembolic disease. Therapeutic management of superficial vein thrombosis (SVT). Consensus statement of the French Society for Vascular Medicine (SFMV).

Superficial vein thrombosis (SVT), a manifestation of venous thromboembolism (VTE), is a common condition, yet of all the types of VTE, it has been the least well studied. Recent studies have challenged the conception that SVT is a benign disease, showing that its risk factors overlap with those of deep-vein thrombosis (DVT) and that it is frequently associated with DVT or pulmonary embolism (PE). In 2010, the CALISTO trial demonstrated the benefit of treatment with fondaparinux at the dose of 2.5mg (one injection per day) for 45days for lower limb SVT. Prior to CALISTO, the treatment of SVT was based on venous compression therapy, nonsteroidal anti-inflammatory drugs (NSAID) and anticoagulation using various therapeutic regimens. Surgery could also be envisaged in certain cases. In CALISTO, the inclusion criteria designed to obtain a homogeneous population meant that numerous questions remained unanswered with respect to SVT occurring in other locations and under other circumstances, notably in pregnant women, patients with renal insufficiency, and patients with recurrent SVT or superficial vein thrombosis less than 5cm long. The aim of this section is to review the current state of knowledge of SVT and to propose or recommend therapeutic strategies for the management of SVT according to the clinical context, the location of the thrombosis, and the presence of particular risk factors.

Unresolved questions on venous thromboembolic disease. Venous thromboembolism (VTE) management in obese patients. Consensus statement of the French Society of Vascular Medicine (SFMV).

Obesity is an alarming worldwide public health issue and is defined as a body mass index (BMI) of 30kg/m2 or more. It is considered as a risk factor for first thrombotic event and is associated with a significant risk of recurrence. Consequently, obese patients are often treated by anticoagulant therapy but data from randomised control trial are scarce. We will review in this narrative review the state of the art of the prescription of anticoagulant for the prevention and treatment of venous thromboembolism (VTE) in obese patients.

Prospective Monitoring of New Drugs in Older Adults with and without Frailty: Near-Real-Time Assessment of Effectiveness and Safety of Oral Anticoagulants in Medicare Data.

BACKGROUND AND OBJECTIVE: Prospective sequential analyses after a new drug approval allow proactive surveillance of new drugs. In the current study, we demonstrate feasibility of frailty-specific sequential analyses for dabigatran, rivaroxaban, and apixaban versus warfarin. METHODS: We partitioned Medicare data from 2011 to 2020 into datasets based on calendar year following the date of drug approval. Each calendar year of data was added sequentially for analysis. We used a new-user, active comparative design by comparing the initiators of dabigatran versus warfarin, rivaroxaban versus warfarin, and apixaban versus warfarin. Patients aged ≥ 65 years with atrial fibrillation without contraindication to the anticoagulants were included. Claims-based frailty index ≥ 0.25 was used to define frailty. The initiators of each direct oral anticoagulant were propensity-score matched to the initiators of warfarin within each frailty status. The effectiveness outcome was ischemic stroke or systemic thromboembolism, and the safety outcome was major bleeding. For each calendar year, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazards models using all data available up to that year. RESULTS: As an example of the results, in the 2020 dataset, compared with warfarin, apixaban was associated with a reduced risk of ischemic stroke or systemic thromboembolism (frail: HR 0.73, 95% CI 0.63-0.85; non-frail: HR 0.65, 95% CI 0.59-0.72) and major bleeding (frail: HR 0.63, 95% CI 0.57-0.69; non-frail: HR 0.59, 95% CI 0.56-0.63) in both frail and non-frail patients. We found evidence for apixaban's effectiveness and safety within 1-2 years after the drug approval in frail older patients. CONCLUSION: Our frailty-specific sequential analyses can be applied to future near-real-time monitoring of newly approved drugs.

Pharmacist Use of a Population Management Dashboard for Safe Anticoagulant Prescribing: Evaluation of a Nationwide Implementation Effort.

BACKGROUND: Direct oral anticoagulants (DOACs) have complex dosing regimens and are often incorrectly prescribed. We evaluated a nationwide DOAC population management dashboard rollout whose purpose includes pharmacist review and correction of off-label dosing prescriptions. METHODS AND RESULTS: Using data from Veterans Health Affairs, we identified all patients prescribed DOACs for atrial fibrillation or venous thromboembolism between August 2015 and December 2019. Sites were grouped on the basis of the timing of moderate-high usage of the DOAC population management tool dashboard. Effectiveness was defined as the monthly rate of off-label DOAC prescribing and the rate of clinical adverse events (bleeding, composite of stroke or venous thromboembolism). Implementation was evaluated as the percentage of off-label DOAC prescriptions changed within 7 days. Among the 128 652 patients receiving DOAC therapy at 123 centers, between 6.9% and 8.6% had off-label DOAC prescriptions. Adoption of the DOAC population management tool dashboard before July 2018 was associated with a decline in off-label dosing prescriptions (8.7%-7.6%). Only 1 group demonstrated a significant reduction in monthly rates of bleeding following implementation. All sites experienced a reduction in the composite of venous thromboembolism or stroke following dashboard adoption. There was no difference in the implementation outcome of DOAC prescription change within 7 days in any of the adoption groups. CONCLUSIONS: Early adoption of the DOAC population management tool dashboard was associated with decreased rates of off-label DOAC dosing prescription and reduced bleeding. Following adoption of the DOAC population management tool dashboard, all sites experienced reductions in venous thromboembolism and stroke events.

Direct Oral Anticoagulants in Antiphospholipid Syndrome-Associated Venous Thromboembolism: Real World Evidence.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. RESULTS: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840). CONCLUSION: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

BACKGROUND: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear. METHODS: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States. Patients with acute ischemic stroke who had received intravenous thrombolysis within 3 hours after symptom onset were assigned to receive intravenous argatroban, eptifibatide, or placebo within 75 minutes after the initiation of thrombolysis. The primary efficacy outcome, the utility-weighted 90-day modified Rankin scale score (range, 0 to 10, with higher scores reflecting better outcomes), was assessed by means of centralized adjudication. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after randomization. RESULTS: A total of 514 patients were assigned to receive argatroban (59 patients), eptifibatide (227 patients), or placebo (228 patients). All the patients received intravenous thrombolysis (70% received alteplase, and 30% received tenecteplase), and 225 patients (44%) underwent endovascular thrombectomy. At 90 days, the mean (±SD) utility-weighted modified Rankin scale scores were 5.2±3.7 with argatroban, 6.3±3.2 with eptifibatide, and 6.8±3.0 with placebo. The posterior probability that argatroban was better than placebo was 0.002 (posterior mean difference in utility-weighted modified Rankin scale score, -1.51±0.51) and that eptifibatide was better than placebo was 0.041 (posterior mean difference, -0.50±0.29). The incidence of symptomatic intracranial hemorrhage was similar in the three groups (4% with argatroban, 3% with eptifibatide, and 2% with placebo). Mortality at 90 days was higher in the argatroban group (24%) and the eptifibatide group (12%) than in the placebo group (8%). CONCLUSIONS: In patients with acute ischemic stroke treated with intravenous thrombolysis within 3 hours after symptom onset, adjunctive treatment with intravenous argatroban or eptifibatide did not reduce poststroke disability and was associated with increased mortality. (Funded by the National Institute of Neurological Disorders and Stroke; MOST ClinicalTrials.gov number, NCT03735979.).

Anticoagulation strategies in patients with coexisting traumatic intracranial hematomas and cerebral venous sinus thrombosis: an observational cohort study.

PURPOSE: Post-traumatic cerebral venous sinus thrombosis (ptCVT) is a rare but serious complication of traumatic brain injury (TBI). Managing ptCVT is challenging due to the concurrent risk of traumatic intracranial hematoma (ICH) expansion. Limited data exists on the safety and efficacy of anticoagulation therapy (ACT) in these cases. METHODS: This single-center observational cohort study included adult TBI patients with concurrent ICH and ptCVT. Low-molecular-weight heparin (LMWH) or heparin infusion was used to treat all ptCVTs based on institutional protocols. The outcomes of interest were hemorrhagic and thrombotic complications. RESULTS: Out of 1,039 TBI-patients admitted between 2006 and 2020, 32 met the inclusion criteria. The median time from injury to ptCVT diagnosis was 24 h. ACT was initiated at a median of 9 h after ptCVT diagnosis. Patients were administered either heparin infusion (n = 8) or LMWH at dosages ranging from 28 to 72% of the therapeutic level (n = 24). There were no hemorrhagic complications, even in patients receiving LMWH at ≥ 50% of the therapeutic dose. Thrombotic complications occurred in 3 patients (9.4%) - two cases of thrombus progression and one venous infarct. The patients who developed thrombotic complications differed from those who did not by having a 17-h delay in ACT initiation after diagnosis or by receiving an initial LMWH dose at 28% of the therapeutic level. CONCLUSION: LMWH at approximately 50% of the therapeutic level was effective for managing ptCVT associated with TBI in our retrospective dataset, with no risk of hematoma expansion. Prospective trials are warranted to confirm these results.