Chronic Anticoagulation in Patients Who Have Atrial Fibrillation Undergoing Outpatient Total Knee Arthroplasty: A Retrospective Matched Cohort Study.

BACKGROUND: Patients who have atrial fibrillation frequently require long-term anticoagulation with warfarin or a direct-acting oral anticoagulant (DOAC), such as apixaban or rivaroxaban, to avoid vascular complications. However, the impact of anticoagulant use on postoperative complications following total knee arthroplasty (TKA) in an outpatient setting has not been thoroughly elucidated. The purpose of this study was to examine the impact of anticoagulant use on early postoperative complications among atrial fibrillation patients undergoing outpatient TKA. METHODS: An insurance claims database was queried to identify all patients who underwent outpatient TKA between January 2010 and April 2022. There were two cohorts of patients, with associated 1:1 matched controls, who had atrial fibrillation and filled a prescription of either warfarin (N = 4,396) or DOAC (N = 5,383) for at least 30 days. The mean age was 70 years (range, 51 to 84 years) and 47.9% were women in the warfarin cohort, while the mean age was 70 years and 49.2% were women in the DOAC cohort. Postoperative 30-day medical and 90-day surgical complications were subsequently compared. RESULTS: Patients on warfarin had a higher incidence of pulmonary embolism (1.1 versus 0.2%, P < 0.001) and a lower incidence of TKA revision (0.1 versus 0.4%, P = 0.003) than matched controls. Similarly, patients on DOACs exhibited a higher incidence of pneumonia (1.4 versus 0.6%, P < 0.001) and myocardial infarction (3.2 versus 1.5%, P < 0.001) and a lower incidence of wound dehiscence (0.1 versus 0.5%, P < 0.001), joint infection (0.4 versus 0.9%, P = 0.002), and TKA revision (0.1 versus 0.4%, P = 0.002) than matched controls. CONCLUSIONS: Atrial fibrillation patients on long-term anticoagulants undergoing outpatient TKA experience higher rates of medical complications and lower rates of surgical complications than matched controls. Thus, patients on long-term anticoagulants may be considered for outpatient TKA, but should be counseled appropriately on associated medical risks.

[Assessing the Impact of in-Hospital Formulary Policies on the Prescription Patterns of Direct Oral Anticoagulants (DOACs)].

Prescribing direct oral anticoagulants (DOACs) with off-label dosage and administration is discouraged due to concerns about their effectiveness and safety. Consequently, our hospital pharmacist established a formulary with physicians for oral anticoagulants. Our study aimed to assess the adherence to this formulary by investigating the rate of appropriate DOAC prescribing. We included patients who were newly prescribed or continued on DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) at our hospital. We calculated the percentage of patients prescribed the correct dosage and administration according to the package insert and compared this across three time periods: pre-intervention (period A; April-September 2019), post-intervention phase 1 (period B; August 2021-January 2022), and post-intervention phase 2 (period C; November 2022-April 2023). We also examined the number of inquiries and consultation requests made by hospital pharmacists regarding DOAC dosage and administration. A total of 782 patients were surveyed (191 in period A, 263 in period B, and 328 in period C). The appropriate prescribing rates for DOACs were 79.1% in period A, 84.4% in period B, and 86.6% in period C. The proportion of cases where hospital pharmacists questioned or consulted doctors about DOAC dosage and administration was 3.7% in period A, 6.1% in period B, and 10.1% in period C. These findings indicate that active intervention by hospital pharmacists using the formulary regarding oral anticoagulant formularies may promote appropriate DOAC use.

Emergent endovascular treatment versus medical treatment for acute large vessel occlusions with nondisabling symptoms.

OBJECTIVES: The aim of this study is to analyze the effectiveness and safety of medical treatment (MT) versus endovascular treatment (EVT) in acute large vessel occlusion patients with mild nondisabling stroke symptoms. METHODS: This study is a multicenter observational study in which data from patients at three stroke centers were prospectively obtained and retrospectively analyzed. Patients were included if they arrived for treatment within 6 h of stroke onset or last known well time and had a baseline National Institutes of Health Stroke Scale (NIHSS) score of ≤5. Primary outcome was modified Rankin Scale (mRS) score 0-2 at 90 days. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), discharge NIHSS score, 90-day all-cause mortality and length of stay. Clinical outcomes were compared through a multivariable logistic regression after adjusting for age, treatment type admission and discharge NIHSS score, admission Alberta Stroke Program Early CT (ASPECT) score and length of stay. RESULTS: Of the 82 patients included in the study, 42 were in the EVT group and 40 were in the MT group. The groups were similar in age (MT:66, EVT:64 age; p = .62), gender (MT:55%, EVT:54.8%; male) admission NIHSS score (MT:2, EVT:3 points; p = .26), ASPECT score (MT:10, EVT:9; p = .15). While discharge NIHSS score was found to be statistically significant between the groups (MT:1, EVT:2; p = .04). There was no difference between the two groups in terms of 90-day mRS scores (MT:1, EVT:1, p = .86) and mortality rates (MT:4, EVT:4; p = .94). In unadjusted analysis, sICH rates were similar between the MT and EVT groups (MT 5%, EVT 7.1%, p = .52). Neurological intensive care unit length of stay (MT:5 days, EVT:2 days p < .001), inpatient clinic length of stay (MT:3, EVT:2 days p = .041), and total length of stay (MT:9 days, EVT:4 days p < .001) were significantly longer in the MT group. CONCLUSIONS: Our multicenter study demonstrated that MT with blood pressure augmentation and anticoagulation at hyperacute stage is an alternative option for emergency large vessel occlusion patients with nondisabling mild stroke symptoms.

Direct Oral Anticoagulants for Rheumatic Heart Disease-Associated Atrial Fibrillation Post-Bioprosthetic Mitral Valve Replacement.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) in preventing ischemic and thromboembolic events may be suboptimal in atrial fibrillation (AF) patients with rheumatic mitral stenosis. However, their safety and effectiveness after mitral valve replacement (MVR) using bioprosthetic valves is unclear. OBJECTIVES: This study sought to evaluate the safety and effectiveness of DOACs vs warfarin among patients with rheumatic heart disease (RHD)-associated AF after bioprosthetic MVR. METHODS: We performed an observational analysis identifying patients with RHD and AF who underwent bioprosthetic MVR. Primary effectiveness and safety outcomes were ischemic events and major bleeding, respectively. Secondary outcomes included all-cause mortality, cardiac thrombosis, myocardial infarction, and all-cause hospitalization. Propensity score matching was performed to account for the differences in baseline characteristics and comorbidities. RESULTS: A total of 3,950 patients were identified; 76% were on warfarin and 24% on DOAC post-MVR. The DOAC group had a higher burden of baseline comorbidities and prior cardiovascular procedures compared with the warfarin group. The propensity score matching balanced baseline characteristics in 1,832 patients (916 in each group), with a mean age of 69 years. At the 5-year follow-up, DOACs were associated with a lower incidence of major bleeding compared with warfarin (HR: 0.76; 95% CI: 0.62-0.94), with no significant difference in ischemic events, mortality, cardiac thrombosis, myocardial infarction, or hospitalization. CONCLUSIONS: Among patients with RHD-associated AF patients post-bioprosthetic MVR, DOACs are associated with lower major bleeding and comparable effectiveness, indicating a potential alternative to warfarin. Further randomized controlled trials are warranted to validate these findings in this population.

Venous Thromboembolism (VTE) in May-Thurner Syndrome: Decision-Making Related to Long-Term Anticoagulation.

May-Thurner syndrome (MTS) involves the compression of the left iliac vein between the right iliac artery anteriorly and the lumbar vertebrae posteriorly. Patients may remain asymptomatic throughout their lives or experience unilateral lower limb swelling and symptoms of deep vein thrombosis (DVT), such as redness and pain in the limb, or features of its complication (pulmonary embolism) such as chest pain or shortness of breath. We present the case of a 34-year-old female exhibiting acute pain and tightness in her left leg, due to DVT of the left common femoral vein, extending up to the pelvic veins, which, on further diagnostic imaging, was found to be due to MTS. The patient was initiated on lifelong anticoagulation to prevent further complications. The rising incidence of MTS, coupled with frequent delays in its diagnosis, highlights the need to raise awareness among healthcare providers, especially acute medics (who are often the first point of contact for the patient) to expand their diagnostic umbrella of differentials to include MTS as a potential cause of such presentations and to look and think beyond DVT of the lower limb. This is especially important in females presenting with non-specific DVT symptoms, as early suspicion and referral to the respective medical teams including vascular medicine, can improve diagnostic accuracy and provide more management options, thereby improving long-term outcomes.

Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease.

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. RESULTS: A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. CONCLUSION: OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

Intravenous Thrombolysis in Patients on Direct Oral Anticoagulants: A Survey of NIH StrokeNet Sites.

BACKGROUND: Patients with suspected ischemic stroke and use of Direct Oral Anticoagulants (DOACs) within 48 hours are excluded from thrombolysis. We aimed to determine practice patterns across institutions in the NIH StrokeNet, a network of hospitals to conduct NIH-funded stroke clinical trials, in the United States. METHODS: A survey was sent electronically to all NIH StrokeNet regional coordinating centers. The survey questions were geared towards understanding practice patterns with intravenous thrombolysis use in patients on DOACs. We reported proportions and percentages answers to the questions. We compared the likelihood of thrombolysis use in patients with recent DOAC ingestion (never vs. all other responses) across characteristics of survey responder using Chi Square. RESULTS: A total of 83 site principal investigators completed the survey; 78.3% would never give thrombolysis to an otherwise eligible patients within 12-24 hours from last DOAC ingestion and 54.2% would never give thrombolysis to an otherwise eligible patient within 24-48 hours from last DOAC ingestion. A higher proportion of vascular neurologists would never give thrombolysis in patients with DOAC ingestion within 12-48 hours compared to other subspecialties (60.7% vs. 36.4%, p = 0.05). Nearly, 80% would change their practice if a well-designed prospective study demonstrated that the symptomatic intracranial hemorrhage rate is not more than 5%. CONCLUSIONS: A well-designed prospective study with a set safety threshold is likely to change practice patterns in giving thrombolysis in patients with recent DOAC ingestion, particularly among vascular neurologists who are more likely to never give thrombolysis in this setting.

RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice.

Combined deficiency of coagulation factor V (FV) and factor VIII (FVIII) is a rare bleeding disease caused by variants in either lectin mannose binding 1 (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) gene. Reducing the level of FVIII by inhibiting the LMAN1-MCFD2 complex may become a new anticoagulant approach. We aimed to find a new therapeutic option for anticoagulation by RNA interference (RNAi) targeting LMAN1 and MCFD2. siRNA sequences with cross-homology between mice and humans were designed based on LMAN1 or MCFD2 transcripts in NCBI and were screened with the Dual-Luciferase reporter assay. The optimal siRNAs were chemically modified and conjugated with three N-acetylgalactosamine molecules (GalNAc-siRNA), promoting their targeted delivery to the liver. The expression of LMAN1 and MCFD2 in cell lines or mice was examined by RT-qPCR and western blotting. For the mice administered with siRNA, we assessed their coagulation function by measuring APTT and the activity of FVIII factor. After administration, siRNAs GalNAc-LMAN1 and GalNAc-MCFD2 demonstrated effective and persistent LMAN1 and MCFD2 inhibition. 7 days after injection of 3mg/kg GalNAc-LMAN1, the LMAN1 mRNA levels reduced to 19.97% ± 3.78%. MCFD2 mRNA levels reduced to 32.22% ± 13.14% with injection of 3mg/kg GalNAc-MCFD2. After repeated administration, APTT was prolonged and the FVIII activity was remarkably decreased. The tail bleeding test of mice showed that the amount of bleeding in the treated group did not significantly increase compared with the control group. Our study confirms that therapy with RNAi targeting LMAN1-MCFD2 complex is effective and can be considered a viable option for anticoagulation drugs. However, the benefits and potential risk of bleeding in thrombophilic mice model needs to be evaluated.

Deep Dissecting Hematoma Requiring Surgical Removal During Veno-Venous Extracorporeal Membrane Oxygenation Management: A Case Report.

Deep dissecting hematoma (DDH) is a disease in which minor trauma leads to the formation of an extensive hematoma. If left untreated, this can result in significant skin necrosis. Therefore, early treatment following a precise diagnosis is essential. However, the complexity of the disease may require differentiating it from soft tissue infections. A 58-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia developed skin complications such as purpura and blisters on his right upper extremity while undergoing veno-venous extracorporeal membrane oxygenation (VV-ECMO). We initially suspected a soft tissue infection or venous perfusion defect caused by the VV-ECMO cannula; however, these conditions were not observed. After making an exploratory incision, we diagnosed the patient with DDH and performed hematoma removal and skin grafting. The initial symptoms of DDH include erythema, swelling, and pain. It is important to differentiate DDH from soft tissue infections, especially necrotizing fasciitis, which is a more urgent condition. Because a surgical incision is necessary for the diagnosis and treatment of DDH, we do not hesitate to perform an exploratory incision to prevent skin necrosis, thereby contributing to early healing.

Oral Anticoagulant Use and Post-Fall Mortality in Long-Term Care Home Residents.

OBJECTIVES: Long-term care (LTC) residents are susceptible to falling and the risk of subsequent morbidity and mortality may be compounded with concurrent anticoagulation use. Uncertainty exists around the benefit and harm of anticoagulation use for residents with a high risk for falls because of concerns of major bleeding complications. We aimed to examine if anticoagulant use increases mortality risk among LTC residents who fall. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Older adults (≥65 years) admitted to a LTC facility in Ontario, Canada between January 1, 2010, and December 1, 2019, who were transferred to emergency departments for fall-related injuries. METHODS: The exposure was the use of an oral anticoagulant (OAC). The primary outcome was mortality within 30 days of transfer. Secondary outcomes were major hemorrhage and care utilization. We used hierarchical logistic regression models to examine the association between the use of OAC and 30-day mortality. RESULTS: There were 56,419 residents transferred to the hospital for a fall, of whom 9611 (17.0%) were on an OAC. At 30 days, 5794 (10.3%) of the cohort had died: 12.0% (1151) on an OAC and 9.90% (4643) not on an OAC (risk difference [RD], 2.1%; 95% CI, 1.40%-2.82%). There were 485 major hemorrhage cases: 1.3% (125) on an OAC and 0.8% (360) not on an OAC (RD, 0.5%; 95% CI, 0.26%-0.74%). Multivariable analysis found no significant association between OAC use and 30-day mortality (odds ratio [OR], 0.98; 95% CI, 0.90-1.06), but an increased risk of major hemorrhage (OR, 1.31; 95% CI, 1.04-1.66). Both groups had similar health system and neurosurgical care utilization. CONCLUSIONS AND IMPLICATIONS: Among LTC residents transferred to the emergency department for fall-related injuries, OACs did not increase the risk of post-fall mortality. OAC prescribing for frail older adults who experience falls should consider their individual risk profile.

Antithrombotic Therapy in Patients with Complex Percutaneous Coronary Intervention and Cardiogenic Shock.

Managing antithrombotic therapy in patients undergoing complex and high-risk in indicated patients, including those treated with complex percutaneous coronary intervention (PCI) or presenting with cardiogenic shock (CS), is challenging. This review highlights the critical role of antithrombotic therapy, during and after PCI, to optimize the efficacy while minimizing risks. Unfractionated heparin remains the mainstay anticoagulant for complex PCI and CS, with bivalirudin as a potential safer alternative. Cangrelor offers consistent antiplatelet effects, especially when timely absorption of oral agents is uncertain.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

Antithrombotic Therapy in Patients with Chronic Coronary Syndromes.

The antithrombotic management of chronic coronary syndrome (CCS) involves a 6-month course of dual antiplatelet therapy (DAPT), followed by chronic aspirin therapy. In patients with a baseline indication for anticoagulation, a variable duration of triple antithrombotic therapy is administered, followed by dual antithrombotic therapy until the sixth month post-percutaneous coronary intervention (PCI), and ultimately a transition to chronic anticoagulation. However, advancements in stent technology reducing the risk of stent thrombosis and a growing focus on the impact of bleeding on prognosis have prompted the development of new therapeutic strategies. These strategies aim to enhance protection against ischemic events in the initial stages after PCI while mitigating the risk of bleeding in the long term. This article delineates the therapeutic strategies outlined in European and American guidelines for CCS management, with special attention to investigational strategies.

Anticoagulant Therapy in Patients Undergoing Acute Pulmonary Embolism Interventions.

Catheter-based interventions and surgical embolectomy represent alternatives to systemic fibrinolysis for patients with high-risk pulmonary embolism (PE) or those with intermediate-high-risk PE who deteriorate hemodynamically. They are indicated when systemic fibrinolysis is contraindicated or ineffective, or if obstructive shock is imminent. Extracorporeal membrane oxygenation can be added to reperfusion therapies or used alone for severe right ventricular dysfunction and cardiogenic shock. These advanced therapies complement but do not replace anticoagulation, which remains the cornerstone in PE management. This review summarizes the evidence and shares practical recommendations for the use of anticoagulant therapy before, during, and after acute PE interventions.

Age is a Risk Factor for Poor Knowledge About Venous Thromboembolism Treatment.

To limit complications and optimize anticoagulant therapy, some units treating venous thrombo embolism offer a formalized educational program to patients. In our clinic we developed a patient questionnaire to target aspects of patient knowledge about their venous thromboembolism (VTE) disease and their treatment that require reinforcement. The VTE questionnaire, composed of 7 questions, has been proposed to adult patients with a diagnosis of deep venous thrombosis or pulmonary embolism requiring anticoagulant therapy for at least 3 months. Patients who completed the VTE questionnaire between March 2022 and February 2023 were included in the present retrospective study. A poor score was defined as < 5 correct answers. We investigated the factors associated with a poor score on the questionnaire, using univariable and multivariable analysis, in order to better target patients education in our unit. A total of 132 patients were included. The majority were men (56.8%) and the mean (±SD) age was 55.4 (±18.3) years. The total score was < 5 in 43.2% of patients. Those with a poor score most frequently lacked knowledge regarding the treatment; only 22.8% of patients knew of the risk of bleeding, 5.3% the contraindication of non steroidal anti inflammatory drugs NSAIDs, and 19.3% knew of the precautions related to physical activity. In multivariate analysis the only factor associated with poor VTE questionnaire score was age ≥ 55 years (OR 2.61, 95%CI 1.14-5.94). Poor knowledge of venous thrombo embolism concerned older patients and particularly treatment-related aspects.

Anticoagulant Impact on Clinical Outcomes of Pulmonary Embolism Compared With Thrombolytic Therapy; Meta-Analysis.

BACKGROUND: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. OBJECTIVES: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. METHOD: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. RESULTS: For sub-massive PE, CDT plus AC significantly reduced in-hospital, 30-day, and 12-month mortality compared to AC alone, odds ratio (OR) of -0.99 (95% CI [-1.32 to -0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [-0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all-cause or in-hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. CONCLUSION: The addition of CDT to AC improves mortality outcomes for sub-massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies.

Clinical implications of combination proton pump inhibitor and triple therapies in patients with atrial fibrillation following percutaneous intervention: a guide for clinicians.

INTRODUCTION: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy. AREAS COVERED: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization. EXPERT OPINION: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.