Direct oral anticoagulant use in hospitalized pediatric patients: Insights from nationwide data.

BACKGROUND: Direct oral anticoagulants (DOACs) have had significant impact on the management of venous thromboembolism (VTE) in adults, but these agents were not approved for use in pediatric patients until 2021. Our objective was to analyze the characteristics of pediatric patients treated with DOACs prior to and following U.S. Food and Drug Administration (FDA) approval for children and evaluate their impact on hospital outcomes. PROCEDURE: We utilized the Epic Cosmos dataset (Cosmos), a de-identified dataset of over 220 million patients, to identify patients aged 1-18 years admitted with a first-occurrence diagnosis of VTE between January 1, 2017 and June 30, 2023. Patients were grouped by anticoagulation received (unfractionated heparin, low molecular weight heparin, and/or DOACs). RESULTS: Among 5138 eligible patients, 18.1% received DOACs as all or part of their anticoagulation treatment, while 81.9% received heparin therapies alone. Patients treated with DOACs were older than patients treated with heparin monotherapy at 17.4 and 13.0 years, respectively. Non-DOAC patients were more likely to have chronic conditions and were less likely to have pulmonary embolism. Patients treated with DOACs demonstrated shorter overall length of stay and duration of intensive care unit (ICU) admission. CONCLUSIONS: DOACs remain infrequently utilized in pediatric patients, especially in those under 13 years old. Initiation on heparin therapy and transition to DOACs remains common, with 80.6% of DOAC patients receiving heparin during their hospitalization. While DOAC monotherapy is not currently endorsed as first-line therapy for DVT or PE in children, it is being used clinically. Further research is needed to clarify the impact of DOAC use on patient adherence, VTE recurrence, and healthcare cost.

"The Failing Watchman": Recurrent Left Atrial Appendage Occlusion Device (LAAOD) Thrombus After Successful Initial Implantation.

A 79-year-old female with chronic atrial fibrillation was being treated with dabigatran (Pradaxa). Pradaxa was discontinued after a significant bleeding episode. A WATCHMAN device was successfully implanted and Pradaxa was started. A transesophageal echocardiogram (TEE) 49 days later showed a 3.6×2.2 cm clot overlying the device. Pradaxa was switched to Coumadin. Subsequent TEEs showed the complete resolution of the thrombus after five months on Coumadin. Coumadin was discontinued. Six months later, TEE showed a large mobile thrombus attached to the left atrial appendage occlusion device (LAAOD). The patient's hypercoagulable workup was negative. Due to recurrent thrombotic events, she was started on apixaban (Eliquis) due to a prior history of bleeding on Coumadin. She is currently on Eliquis with no further episodes of bleeding or device thrombus.

Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry.

BACKGROUND: The DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). OBJECTIVE: To compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. METHODS: We included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. RESULTS: A total of 2834 AF patients (median age [IQR] 69 [62-77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55-0.70; DOAC score AUC 0.62, 95 % CI 0.59-0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. CONCLUSION: In a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.

Adherence to oral anticoagulants in patients with non-valvular atrial fibrillation: the role of patients' characteristics and out-of-pocket payments.

BACKGROUND: Recent practice guidelines favor direct oral anticoagulants (DOACs) over warfarin for primary stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, challenges persist in Iraq's private pharmaceutical sector. DOACs have been sold at high and inconsistent retail prices and lack insurance coverage, leading to significant out-of-pocket (OOP) costs. The objective of this study is to investigate the impact of OOP costs on oral anticoagulants (OAC) adherence among NVAF patients. RESEARCH DESIGN AND METHODS: This multicenter cross-sectional study interviewed 359 eligible patients attending three private cardiology clinics within Iraq's southern region from December 2022 to February 2023. The 8-item Morisky Adherence Scale evaluated patient adherence. Statistical analyses, including descriptive analysis, ANOVA, and chi-square. p < 0.05 was considered statistically significant. RESULTS: The most frequently prescribed OAC were DOACs (62.8%). Patient adherence level to OAC was chiefly medium (54.6%) with no significant difference in adherence based on OAC type. Patient adherence was significantly associated with monthly income (p = 0.001), number of daily pills (p = 0.006), and OACs' average monthly cost (p = 0.011). CONCLUSION: Addressing the issue of cost-related non-adherence to OACs requires multiple actions. These include ensuring comprehensive health insurance coverage for OACs, increasing the use of affordable generic alternatives, and establishing effective cost-related discussions between healthcare providers and patients.

Time trends in stroke risk management among high-risk patients with non-valvular atrial fibrillation in Australia between 2011-2019.

Background: Atrial fibrillation (AF) is associated with stroke. Major changes to AF management recommendations in 2016-2018 advised that: 1. Stroke risk be estimated using the CHA2DS2-VA score; 2. Antiplatelet agents (APAs) do not effectively mitigate stroke risk; 3. Anticoagulation is prioritised above bleeding risk among high-risk patients; and 4. Non-vitamin K oral anticoagulants (NOACs) are used as first-line anticoagulants. Aim: To examine trends in stroke risk management among high-risk patients with non-valvular AF in Australia between 2011-2019. Method: De-identified data of patients were obtained from 164 separate general practices. Data included information on patient demographics, diagnoses, health risk factors and recent prescriptions. Patients with a diagnosis of non-valvular AF were identified and stroke risk was calculated by CHA2DS2-VA score. High risk patients (i.e. CHA2DS2-VA ≥ 2) were categorised as being managed by oral anticoagulants (OACs, i.e., warfarin or NOACs), APAs only, or neither (i.e., no OACs or APAs) and time trends in prescribing were examined. Multivariate analyses examined the characteristics of patients receiving the guideline recommended OAC management. Results: Data were available for 337,964 patients; 8696 (2.6 %) had AF. Most patients with AF (85.8 %, n = 7116) had high stroke risk. The proportion of high-risk patients managed on OACs increased from 56.7 % in 2011 to 73.7 % in 2019, while the proportion prescribed APAs declined from 31.1 % to 14.0 %. Those receiving neither treatment remained steady (around 12 %). Overall, 26.3 % of patients were inadequately anticoagulated at the end of the study period. There were no age or gender differences in receiving the guideline-recommended therapy, and patients with comorbidities associated with increased stroke risk were more likely to receive OAC therapy. Conclusions: Stroke risk management among patients with AF has improved between 2011-2019, however there is still scope for further gains as many high-risk patients remain inadequately anticoagulated. Better stroke risk assessment by clinicians coupled with addressing practitioner concerns about bleeding risk may improve management of high-risk patients.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Introduction: Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Methods: Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. Results: A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. Conclusion: In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

To treat or not to treat: a comparative effectiveness analysis of oral anticoagulant outcomes among U.S. nursing home residents with atrial fibrillation.

BACKGROUND: Nursing home residents with atrial fibrillation are at high risk for ischemic stroke, but most are not treated with anticoagulants. This study compared the effectiveness and safety between oral anticoagulant (OAC) users and non-users. METHODS: We conducted a new-user retrospective cohort study by using Minimum Data Set 3.0 assessments linked with Medicare claims. The participants were Medicare fee-for-service beneficiaries with atrial fibrillation residing in US nursing homes between 2011 and 2016, aged ≥ 65 years. The primary outcomes were occurrence of an ischemic stroke or systemic embolism (effectiveness), occurrence of intracranial or extracranial bleeding (safety) and net clinical outcome (effectiveness or safety outcomes). Secondary outcomes included total mortality and a net clinical and mortality outcome. Cox proportional hazards and Fine and Grey models estimated multivariable adjusted hazard ratios (aHRs) and sub-distribution hazard ratios (sHRs). RESULTS: Outcome rates were low (effectiveness: OAC: 0.86; non-users: 1.73; safety: OAC: 2.26; non-users: 1.75 (per 100 person-years)). OAC use was associated with a lower rate of the effectiveness outcome (sHR: 0.69; 95% Confidence Interval (CI): 0.61-0.77), higher rates of the safety (sHR: 1.70; 95% CI: 1.58-1.84) and net clinical outcomes (sHR: 1.20; 95% CI: 1.13-1.28) lower rate of all-cause mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61), and lower rate of the net clinical and mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61). Warfarin users, but not DOAC users, had a higher rate of the net clinical outcome versus OAC non-users. CONCLUSIONS: Our results support the benefits of treatment with OACs to prevent ischemic strokes and increase longevity, while highlighting the need to weigh apparent benefits against elevated risk for bleeding. Results were consistent with net favorability of DOACs versus warfarin.

Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients (BMI ≥ 30 kg/m2) with Atrial Fibrillation or Venous Thromboembolism: An Updated Systematic Review and Meta-Analysis.

Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

Effect of direct oral anticoagulant therapy on pulmonary artery clot dissolution in intermediate high-risk pulmonary thromboembolism.

BACKGROUND: Direct oral anticoagulants are the established drugs for treating pulmonary thromboembolism. The advantage of direct oral anticoagulants over conventional therapy for clot lysis and right ventricular unloading in the acute phase remains unclear. This study aimed to evaluate the effect of acute treatment with direct oral anticoagulants on clot dissolution and right ventricular unloading in intermediate high-risk pulmonary thromboembolism. METHODS: Thirty patients with intermediate high-risk pulmonary thromboembolism admitted between November 2012 and December 2018 were included; 21 and 9 were treated with direct oral anticoagulants and conventional therapy, respectively. We compared the efficacy of clot dissolution and right ventricular unloading for intermediate high-risk pulmonary thromboembolism between direct oral anticoagulant and conventional therapy in the acute phase. Efficacy was assessed by computed tomography obstruction index, right/left ventricular ratio, and brain natriuretic peptide levels between baseline and at discharge. RESULTS: Computed tomography obstruction index, right ventricular/left ventricular ratio, and brain natriuretic peptide levels were significantly lower at discharge than at admission in both groups. The rate of improvement in computed tomography obstruction index was significantly higher in the direct oral anticoagulant therapy group than in the conventional therapy group (64 ± 15% vs. 47 ± 16%; p = 0.01). There were no significant differences in the rate of improvement in right ventricular/ left ventricular ratio and brain natriuretic peptide levels between the two groups. CONCLUSIONS: Compared with conventional therapy, direct oral anticoagulants significantly reduced pulmonary artery clot burden conventional therapy in the acute treatment of intermediate high-risk pulmonary thromboembolism.

Analysis of hemorrhagic drug-drug interactions between P-gp inhibitors and direct oral anticoagulants from the FDA Adverse Event Reporting System.

BACKGROUND: Limited understanding exists regarding the hemorrhagic risk resulting from potential interactions between P-glycoprotein (P-gp) inhibitors and direct oral anticoagulants (DOACs). Utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) data, we analyzed hemorrhagic adverse events (AEs) linked with the co-administration of P-gp inhibitors and DOACs, aiming to offer guidance for their safe and rational use. METHODS: Hemorrhagic events associated with P-gp inhibitors in combination with DOACs were scrutinized from the FAERS database. Hemorrhagic signals mining was performed by estimating the reported odds ratios (RORs), corroborated by additive and multiplicative models and a combination risk ratio (PRR) model. RESULTS: Our analysis covered 4,417,195 cases, revealing 11,967 bleeding events associated with P-gp inhibitors. We observed a significantly higher risk of bleeding with the combination of apixaban and felodipine (ROR 118.84, 95% CI 78.12-180.79, additive model 0.545, multiplicative model 1.253, PRR 22.896 (2450.141)). Moreover, consistent associations were found in the co-administration analyzes of rivaroxaban with dronedarone and diltiazem, and apixaban with losartan, telmisartan, and simvastatin. CONCLUSION: Our FAERS data analysis unveils varying degrees of bleeding risk associated with the co-administration of P-gp inhibitors and DOACs, underscoring the importance of vigilance about them in clinical practice.

Impact of prior oral anticoagulation on admission stroke severity in patients with atrial fibrillation.

BACKGROUND AND AIMS: In patients with atrial fibrillation, oral anticoagulation therapy is indicated for both primary and secondary prevention of stroke/systemic embolism. Though direct oral anticoagulants with greater safety and efficacy than warfarin were introduced into clinical practice at the beginning of the last decade, even now not all patients with AF have adequate preventative anticoagulant treatment. The primary goal of this study was to evaluate the impact of prior use of oral anticoagulants on admission stroke severity in those with AF. Other aims were, inter alia, to assess the trend in atrial fibrillation prevalence in the years of the HISTORY trials 2012-2021 carried out in the Czech Republic and use of oral anticoagulants (OAC) in ischemic stroke (IS) patients. METHODS: We analyzed consecutive ischemic stroke patients who had been enrolled in the HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (identifier NCT01541163) in the year 2012 and carried out a yearly comparison (detailed in the text). RESULTS: In total, there were 1059 patients (55.9% males, mean age 71.7±12.8). There was no significant difference over the time period in rate of known (18.3 vs. 16.5%, P=0.442) or newly detected AF (17.0 vs. 16.0%, P=0.665), but sigificantly more patients with known AF were treated with oral anticoagulants before IS in the year 2021 (32.1 vs. 70.7%, P<0.0001), and direct oral anticoagulants (3.6 vs. 35.4%, P<0.0001). The number of patients with atrial fibrillation had not changed significantly over the years (26.2 vs. 31.3%). Patients on OAC had a lower median admission score on the National Institutes of Health Stroke Scale (NIHSS) than those not using an oral anticoagulant (6 vs. 16, P=0.0004) in 2021. CONCLUSIONS: There was no significant upward trend in atrial fibrillation in stroke patients admitted between 2012 and 2021, but patients with known AF were significantly more frequently treated with oral anticoagulants and direct oral anticoagulants (DOAC) in 2021. Patients on OAC had lower admission NIHSS scores than those not using any anticoagulent in the year 2021. The difference in the median admission NIHSS between the patients on OAC and those without OAC treatment was not significant in the year 2012 (6 vs. 12, P=0.066). This might be related to the fact that substantially fewer patients in 2012 were on DOACs, which are considered more effective than warfarin.

Clinical effects of direct oral anticoagulants in elderly patients with a bioprosthetic valve and atrial fibrillation.

BACKGROUND: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited. METHODS: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events. RESULTS: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years. CONCLUSIONS: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF.

Direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer-associated venous thrombosis: a cost-effectiveness analysis.

Background: Direct oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system. Methods: A Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: Relative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY. Conclusions: DOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.

Reversal of direct oral anticoagulants: Guidance from the SSC of the ISTH: R1.

The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs compared to vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet-alfa and idarucizumab are the currently approved specific reversal agents for oral FXa inhibitors and dabigatran, respectively. Our prior guidance document was published in 2106, but with more information available on the utility and increased use of these reversal agents and other bleeding management strategies, we have updated this ISTH guidance document on DOAC reversal. In this narrative review, we compare the mechanism of action of specific and non-specific reversal agents, review the clinical data supporting their use, and provide guidance on when reversal is indicated. In addition, we briefly discuss the reversal of oral FXIa inhibitors, a new class of DOACs currently under clinical development.

Direct Oral Anticoagulants and Concomitant Anti-seizure Medications: A Retrospective, Case-Control Study in a Real-World Setting.

PURPOSE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls. METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province. FINDINGS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group. IMPLICATIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.

Advances in the medical treatment and diagnosis of intracranial hemorrhage associated with oral anticoagulation.

INTRODUCTION: With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. AREAS COVERED: In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. EXPERT OPINION: Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4-8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available.

Safety and efficacy of concomitant treatment with non-vitamin K antagonist oral anticoagulants and antiseizure medications: A propensity score matching cohort study.

Research on cerebrovascular events in atrial fibrillation (AF) patients taking non-vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications (n = 188), AF patients on NOACs (n = 298), and epilepsy patients on ASMs (n = 50), with a 3-year follow-up. Propensity score matching adjusted for cardiovascular risk differences. The primary outcomes were ischemic stroke, transient ischemic attack, and major bleeding. Results showed the ASM+NOAC group had a higher risk of primary outcomes compared to the NOAC-only group (5.68% vs. 1.18%, hazard ratio = 5.72, 95% confidence interval = 2.22-14.73), with no events in the ASM-only group. This suggests an increased risk for patients on combined NOAC and ASM therapy, underlining the need for careful drug interaction consideration.

Clinical Care Pathway and Management of Major Bleeding Associated with Nonvitamin K Antagonist Oral Anticoagulants: A Modified Delphi Consensus from Saudi Arabia and UAE.

Background: The nonvitamin K antagonist oral anticoagulants (NOACs) have become the mainstay anticoagulation therapy for patients requiring oral anticoagulants (OACs) in the Gulf Council Cooperation (GCC) countries. The frequency of NOAC-associated major bleeding is expected to increase in the Emergency Department (ED). Nonetheless, we still lack local guidelines and recommendations for bleeding management in the region. The present Delphi-based consensus aims to establish a standardized and evidence-based clinical care pathway for managing NOAC-associated major bleeding in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE). Methods: We adopted a three-step modified Delphi method to develop evidence-based recommendations through two voting rounds and an advisory meeting between the two rounds. A panel of 11 experts from the KSA and UAE participated in the consensus development. Results: Twenty-eight statements reached the consensus level. These statements addressed key aspects of managing major bleeding events associated with NOACs, including the increased use of NOAC in clinical practice, clinical care pathways, and treatment options. Conclusion: The present Delphi consensus provides evidence-based recommendations and protocols for the management of NOAC-associated bleeding in the region. Patients with major DOAC-induced bleeding should be referred to a well-equipped ED with standardized management protocols. A multidisciplinary approach is recommended for establishing the association between NOAC use and major bleeding. Treating physicians should have prompt access to specific reversal agents to optimize patient outcomes. Real-world evidence and national guidelines are needed to aid all stakeholders involved in NOAC-induced bleeding management.