Outcomes of left atrial appendage closure versus oral anticoagulant therapy in patients with atrial fibrillation: an updated meta-analysis of randomized control trials.

BACKGROUND: The purpose of this study is to compare the clinical results of Left Atrial Appendage Closure (LAAC) and oral anticoagulation (OAC) in individuals with AF. METHODS: For randomized controlled trials (RCTs) comparing the clinical results of OAC to LAAC in patients with atrial fibrillation (AF), we searched PubMed, ScienceDirect, and Cochrane. The included publications were subjected to meta-analyses using Review Manager v5.4. RESULTS: In comparison to OAC, LAAC was linked with a decreased incidence of all stroke (OR 0.68; 95% CI 0.55-0.84; p = 0.0004). LAAC was also linked to a decreased risk of hemorrhagic stroke (OR 0.20, 95% CI 0.07-0.55; p = 0.002). There is no statistically significant difference between the two groups in terms of ischemic stroke (OR 1.05; 95% CI 0.59-1.84; p = 0.88) or systemic embolization (OR 1.02; 95% CI 0.42-2.46; p = 0.97). CONCLUSIONS: According to our meta-analysis, the LAAC was less likely than the OAC to have a complete or hemorrhagic stroke. For the two groups, however, there was no difference in the risk of ischemic stroke or systemic embolization.

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), 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.

Anticoagulant-related bleeding as a sign of underlying tumoural lesions in patients with atrial fibrillation: a nationwide cohort study.

Aims: Bleeding events are a well-known complication of oral anticoagulant (OAC) use in patients with atrial fibrillation (AF). While these are undesirable, bleedings could have a warning potential for underlying tumoural lesions. Therefore, we aimed to investigate the association between anticoagulant-related bleeding and newly diagnosed tumoural lesions in a nationwide cohort study. Methods and results: Using Belgian nationwide data, AF patients without any tumoural lesions were included when initiating OACs between 2013 and 2019. The absolute and relative risks of newly diagnosed tumoural lesions were investigated in OAC users with vs. without an OAC-related bleeding event. Analyses were additionally stratified by tumoural lesion, location-specific bleeding, and OAC type. A total of 230 386 OAC users were included, among whom 35 192 persons were diagnosed with a tumoural lesion during follow-up. Persons with a clinically relevant bleeding during OAC use had a tumoural lesion incidence of 15.33 per 100 person-years compared to an incidence of 5.22 per 100 person-years in persons without bleeding. Site-specific gastrointestinal, urogenital, respiratory, and intracranial bleeding events were respectively associated with a significantly increased risk of incident gastrointestinal [adjusted hazard ratio (aHR) 8.13 (95% confidence interval (CI): 7.08-9.34)], urological [aHR 12.73 (95% CI: 10.56-15.35)], respiratory [aHR 4.91 (95% CI: 3.24-7.44)], and intracranial tumoural lesions [aHR 27.89 (95% CI: 16.53-47.04)]. Conclusion: Bleeding events in AF patients initiated on OAC were associated with an increased risk of tumoural lesions. Therefore, OAC-related bleeding events could unmask an underlying tumoural lesion.

[Five-year outcomes in patients with ischemic stroke or transient ischemic attack after widespread use of direct oral anticoagulants].

The long-term outcomes of patients with stroke or transient ischemic attack (TIA) after widespread use of direct oral anticoagulants (DOACs) were investigated. Patients with ischemic stroke or TIA admitted between April 2014 and September 2015 were prospectively enrolled and followed for up to 5 years after the index stroke or TIA. Primary outcome measures were any cause of death and stroke recurrence. A total of 555 consecutive patients (323 men; mean age, 75 years; ischemic stroke, n = 520; TIA, n = 35) were analyzed. The follow-up rate was 93%, and the mean follow-up period was 48 ± 20 months. DOACs accounted for 52% of anticoagulants at discharge. During follow-up, 162 patients died, for cumulative mortality rates of 30% (particularly, 53% in cardioembolism) at 5 years. Recurrent stroke occurred in 90 patients, with cumulative risks of stroke recurrence of 19% at 5 years. The 5-year mortality rate remain even after widespread use of DOACs, and further treatment approaches are warranted.

[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.

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.

Comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban in dogs.

BACKGROUND: Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown. HYPOTHESIS: Compare the PK/PD of clinical dosing regimens of PO apixaban and rivaroxaban administered repeatedly to healthy dogs and assess the effect of abrupt drug discontinuation on coagulation. ANIMALS: Six University-owned, purpose-bred, middle-aged, mixed-breed dogs (4 male, 2 female). METHODS: Dogs were given apixaban or rivaroxaban PO at 0.5 mg/kg q12h for 7 days with a 14-day washout period between drugs. Plasma drug concentrations were quantitated, and anticoagulant effects were measured using clotting times, calibrated anti-Xa bioactivity assays, and measurements of thrombin generation. The potential for rebound hypercoagulability was assessed by measuring D-dimers, thrombin-antithrombin (TAT) complexes, and antithrombin activity after drug discontinuation. RESULTS: Plasma drug concentrations and anti-Xa bioactivities were closely correlated for both drugs, but drug concentrations varied considerably among dogs, despite consistent dose regimens. Thrombin generation variables were significantly correlated with the anti-Xa bioactivity of both drugs and no significant differences in the effects of apixaban and rivaroxaban on thrombin generation were observed. Drug discontinuation had no effect on D-dimer concentrations. The concentration of TAT complexes decreased after apixaban discontinuation and did not change after rivaroxaban discontinuation. CONCLUSIONS AND CLINICAL IMPORTANCE: Repeated PO administration of apixaban or rivaroxaban to healthy dogs produced comparable anticoagulant effects measured by inhibition of thrombin formation. Rebound hypercoagulability after drug discontinuation was not observed and weaning of these drugs in clinical patients might not be necessary.

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 h 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 h from last DOAC ingestion and 54.2 % would never give thrombolysis to an otherwise eligible patient within 24-48 h from last DOAC ingestion. A higher proportion of vascular neurologists would never give thrombolysis in patients with DOAC ingestion within 12-48 h 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 >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.

Treatment of atrial fibrillation and venous thromboembolism with factor Xa inhibitors in severely obese patients.

BACKGROUND: A paucity of data exists to support the use of factor (F)Xa inhibitors in severely obese patients with a weight of ≥150 kg or body mass index (BMI) of ≥50 kg/m2. OBJECTIVES: The purpose of this study was to evaluate whether FXa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI of ≥50 kg/m2 and/or weight of ≥150 kg. METHODS: This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a FXa inhibitor or warfarin. The primary effectiveness outcome was composite odds of stroke, systemic embolism, or VTE; the primary safety outcome was odds of major bleeding. Secondary outcomes included incidence of stroke or systemic embolism, VTE, major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, change in anticoagulation, and total number of hospital encounters. Outcomes were assessed for 12 months following initiation of study drug. RESULTS: A total of 1736 patients were included. The mean weight and BMI of the overall cohort were 164.4 kg and 54.6 kg/m2, respectively. There was no difference in odds of stroke, systemic embolism or VTE (odds ratio, 1.005; 95% CI, 0.6-1.68), or major bleeding (odds ratio, 0.9; 95% CI, 0.47-1.7) between groups. CONCLUSION: These data suggest that apixaban and rivaroxaban are safe and effective alternatives to warfarin for the treatment of AF and/or VTE in individuals with a BMI of ≥50 kg/m2 and/or weight of ≥150 kg.

Out-of-Pocket Expenditure and Challenges Faced by Patients Undergoing Heart Valve Replacement in Follow-Up Care at a Tertiary Care Center in South India: A Mixed Methods Study.

Background Heart valve replacement surgery is one of the most commonly performed cardiac surgeries in India. Post-surgery, the patient requires lifetime anticoagulation therapy with regular follow-up, leading to financial and nonfinancial burdens for the patients. This study aimed to determine the out-of-pocket (OOP) expenditure (OOPE) for follow-up visits to the heart valve clinic and explore and assess the challenges faced by patients during these follow-ups. Methodology This mixed methods study was conducted at a tertiary care center from June 2018 to August 2018, focusing on patients attending the Valve Replacement clinic. The qualitative component of the study involved conducting three focus group discussions, which were transcribed and manually analyzed using thematic analysis to generate categories. The monthly OOPE and the proportion of irregular patients were assessed using a pretested and validated questionnaire developed based on the findings from the qualitative study. The data from the quantitative study were entered into EpiData version 3.1 (EpiData, Odense, Denmark) and analyzed using Stata 14 (StataCorp., College Station, TX). Results The median (interquartile range [IQR]) total OOPE for patients was Rs. 765 (475-1,100). The median (IQR) direct and indirect expenditures were Rs. 420 (210-600) and Rs. 590 (330-948), respectively. The patients faced difficulties in the categories of financial, travel, hospital, family, and personal. Out of a total of 143 participants, 86 (60.14%) had incurred catastrophic health expenditures. The cost also significantly increased with the presence of an accompanying person and longer travel durations. Conclusions The major difficulties faced by the patients were distance and expense. Telemedicine can help overcome these challenges by decentralizing follow-up care to the primary care level.

Bibliometric and visualized analysis on hip fracture surgery and venous thromboembolism.

Background: Hip fractures primarily occur in older people and represent a significant public health issue due to their high incidence and mortality rate. The concurrent occurrence of venous thromboembolism (VTE) during the perioperative period exacerbates the threat to patient health. Methods: We retrieved all articles related to hip fracture surgery and venous VTE from the Web of Science core collection database from 2000 to 2023. For bibliometric analysis, we extracted relevant information, including year of publication, country, institution, journal, impact factor, title, author, category, reference, keywords, number of citations, average number of citations, and H-index. Results: A total of 1079 articles were retrieved, with 67 countries, 341 institutions, and 256 journals participating in research on hip fracture surgery and venous thromboembolism. The overall research showed an increasing trend. The United States, Harvard University, Injury-International Journal of The Care of The Injured, and Lassen MR are the leading country, institution, journal, and author respectively, in terms of publication. Research directions in this field mainly include the impact of preoperative anticoagulation on fracture surgery, intraoperative blood protection strategies, and postoperative prevention and treatment of VTE. Hotspots and trends in research include the relationship between direct oral anticoagulants and surgical timing, perioperative blood protection, intertrochanteric fractures, and geriatric traumatic fractures. Conclusions: This study constructed the knowledge structure of hip fracture surgery and VTE and identified research hotspots and trends. Future research should focus on developing a prediction system for VTE in hip fracture surgery to guide individualized prevention and treatment.

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.

Assays for Monitoring Apixaban and Rivaroxaban in Emergency Settings, State-of-the-Art Routine Analysis, and Volumetric Absorptive Microsamples Deliver Discordant Results.

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC's): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory. For VAMS samples, dried plasma and whole blood calibrators were found to be suitable, and a cycle run for seven days could be implemented for rational and economic sample processing. The anti-Xa chromogrenic assay and the LC-MS/MS method delivered discordant plasma analyte concentrations. Moreover, the lack of agreement between plasma and VAMS concentrations was observed. Clinical laboratories must be aware of the differences between the performance of apixaban and rivaroxaban LC-MS/MS and anti-Xa assays. Hematocrit must always be measured along with VAMS samples to obtain accurate results.

Comparison of direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for venous thromboprophylaxis after radical cystectomy: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Radical cystectomy in bladder cancer patients can result in postoperative complications, including venous thromboembolism (VTE), with an incidence reported between 3% and 11.6%. Although low-molecular-weight heparin (LMWH) is the recommended prophylactic treatment, challenges such as financial constraints and patient adherence remain. Direct Oral Anticoagulants (DOACs) present an alternative, but their comparative efficacy and safety against LMWHs in preventing VTE after radical cystectomy need further evaluation. This study aims to compare the efficacy and safety of LMWHs vs. DOACs for VTE prophylaxis following radical cystectomy. MATERIALS AND METHODS: A systematic search was performed across 3 electronic databases to identify relevant studies utilizing DOACs and LMWHs for VTE prophylaxis after radical cystectomy. The primary outcomes of interest were VTE and bleeding events. Fixed-effect models were employed to summarize the outcomes, with results presented as odds ratios (OR) and their corresponding 95% confidence intervals (CI). RESULTS: The analysis included a total of 541 patients from three studies. The pooled data indicated that patients on DOACs had a statistically nonsignificant lower odds of VTE (OR 0.41 [95% CI 0.13-1.36], P = 0.15) and a statistically nonsignificant higher odds of bleeding events (OR 3.03 [95% CI 0.53-17.23], P = 0.21). CONCLUSIONS: Our findings suggest that DOACs are comparable to LMWHs in terms of VTE and bleeding events for thromboprophylaxis following radical cystectomy. The choice of prophylactic agent can be guided by patient preference and clinical judgment. However, additional randomized controlled trials with larger sample sizes are necessary to confirm these findings.

Oral anticoagulation in patients with hypertrophic cardiomyopathy and non-valvular atrial fibrillation in Japan.

AIMS: There are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan. METHODS: This retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest-neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE). RESULTS: After PS matching, 2955 DOAC- and 1603 warfarin-treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with ß-blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50-1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78-1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47-0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22-3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10-3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05-4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22-2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24-2.83). CONCLUSIONS: DOAC-treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin-treated patients. Prior stroke was shown to augment stroke risk by approximately three-fold. This large real-world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

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.

Dual direct oral anticoagulant therapy in challenging thrombosis: a case series.

Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.