Like any major operation, sleeve gastrectomy (SG) has its reported postoperative complications. Among them are venous thromboembolic complications (VTE) that may predispose to mortality. Despite the proven efficacy of the traditional anticoagulants, such as low molecular weight heparins (LMWHs) for VTE management, they have their limitations. Direct oral anticoagulants (DOACs) have been currently adopted for the management of VTE. We conducted this study to evaluate the efficacy and safety of apixaban against VTE after laparoscopic sleeve gastrectomy in comparison with LMWH.

This was a randomized controlled trial that included 100 adult patients who underwent SG and received LMWH (Group A) or apixaban (Group B) for VTE prophylaxis. We recorded and analyzed the postoperative events up to the 30th day after surgery.

This study included Group A (n = 50) and Group B (n = 50). No VTE occurred in either group (0%). Postoperative bleeding was encountered in one patient of each group (2%). The follow-up venous Doppler study was unremarkable in the two groups.

Apixaban was shown to be comparable to LMWH for the prevention of VTE after LSG with similar efficacy and safety making it a promising alternative to LMWH in patients undergoing bariatric surgery.

Background/Objectives: The use of direct oral anticoagulants (DOACs) in obese patients is scarcely studied despite having many advantages over warfarin. Consequently, this study aims to assess the real-world safety and effectiveness of apixaban compared to warfarin in treating atrial fibrillation (AF) in obese patients. Methods: A retrospective cohort study examined consecutive AF patients with a BMI of ≥ 30 kg/m2 treated with apixaban or warfarin. Patients were started on these medications between January 2015 and December 2021. Efficacy outcomes included ischemic stroke and venous thromboembolism (VTE) occurrences, while safety outcomes encompassed bleeding incidents and mortality rates. Outcomes were assessed following propensity score matching. Results: We identified 876 patients treated with either apixaban (414) or warfarin (462). Their mean age was 76.9, with a mean CHA2DS2VASc score of 4.9 ± 1.97. After matching and compared to warfarin, apixaban was correlated with a lower incidence of all-cause mortality (19.7% vs. 33.7%, p < 0.001). The incidences of stroke, venous thromboembolism (VTE), and bleeding events were (4.7% vs. 4.7%, p = 1.000), (1.0% vs. 2.6%, p = 0.107), and (3.9% vs. 6.2%, p = 0.139), respectively. Using Cox-regression model, apixaban was associated with lower mortality risk (HR = 0.728, 95% CI: 0.55-0.97; p = 0.030) which remained significant after adjusting for the conventional cardiovascular risk factors and BMI values. Conclusions: Apixaban is associated with a trend of reduced incidence of thromboembolism among obese patients with atrial fibrillation and significantly lowers all-cause mortality. Despite earlier concerns, the use of apixaban is an effective and safe alternative to warfarin among obese patients with AF.

Oral anticoagulant therapy (OAT) is critical for managing thromboembolic disorders, but adherence challenges significantly impact its effectiveness and patients' quality of life (QoL). This study explores the predictors of adherence and their effects on QoL among OAT users in Egypt.

This multi-center cross-sectional descriptive study with an analytical component was conducted at Mansoura University Hospital and Ain Shams University Hospital. Participants were adults over 18 years old, on OAT for at least one month, who provided informed consent. Convenience sampling was used to recruit 212 participants. Data were collected using a survey that included socio-demographic details, the Arabic Version of the Adherence to Refills and Medications Scale (ARMS), and the WHOQOL-BREF questionnaire. Statistical analyses included descriptive statistics, chi-square tests, Student's t-tests, and multivariate logistic regression.

The study included 212 participants, with an average age of 55 years, 57% female and 43% male. Among the participants, 25.5% were adherent to their anticoagulant regimen, while 74.5% were non-adherent. Adherence was significantly higher among NOAC users (44.4%) compared to warfarin users (19.0%). Key predictors of adherence included the use of NOACs (OR = 2.7), residency in rural areas (OR = 2.4), and having first-degree relatives in medical specialties (OR = 2.4). Quality of life scores were significantly higher for NOAC users in psychological, social, and environmental domains compared to warfarin users. The overall QoL score was also higher in NOAC users. Poorer adherence was associated with lower scores in these QoL domains.

Our study indicates that NOACs enhance adherence and quality of life relative to VKAs. Key adherence predictors include NOAC use, rural residency, and having relatives in medical professions. Educational level, initially significant, did not persist as a predictor in multivariate analysis. Targeted strategies are needed to improve adherence and patient outcomes.

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies-e.g., osocimab, anti-sense oligonucleotides-e.g., fesomersen, and small molecule inhibitors-e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

Background: Management of oral anticoagulation (OAC) can be challenging, such as in complex cases of nonvalvular atrial fibrillation (NVAF).Materials & methods: A Delphi study comprising two rounds was used for gathering expert opinion through an online questionnaire (83 items grouped in 8 dimensions) on OAC management in specific clinical settings.Results: Consensus was reached for 79 items (95%) in round 1. Experts recommended direct-acting oral anticoagulants (DOACs) for pericardioversion, uninterrupted OAC for catheter ablation, and dual therapy with a DOAC and clopidogrel after percutaneous coronary intervention. They also recommended restarting OAC with a DOAC after an intracranial haemorrhage.Conclusion: The expert-based recommendations obtained may contribute to standardizing and guiding the management of OAC in complex clinical situations in cardiology.

Patients with atrial fibrillation are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and atrial fibrillation clinical outcomes using methods not previously applied to this problem.

Retrospective observational cohort study of incident cases of atrial fibrillation from population-based administrative data over 23 years. The exposure of interest was proportion of days covered during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, transient ischemic attack, or death and several secondary outcomes. A total of 44 172 patients were included with median follow-up of 6.7 years. For direct OACs (DOACs), each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, transient ischemic attack, or death. For vitamin K antagonist (VKA) the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the proportion of days covered spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels.

Even small reductions in OAC adherence in patients with atrial fibrillation were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.

Since the introduction of direct oral anticoagulants (DOACs) and their comparison with vitamin K antagonists (VKAs), conflicting results have been reported regarding the optimal treatment for left ventricular thrombosis (LVT).

In this meta-analysis, we intend to comprehensively evaluate the safety and efficacy of these treatments.

All clinical trials and cohorts that compared the efficacy or safety of VKAs with DOACs in the treatment of LVTs were systematically searched until April 15, 2023.

The results of 32 studies with a pooled sample size of 4213 patients were extracted for meta-analysis. DOACs, especially rivaroxaban and apixaban, cause faster resolution, lower mortality, and fewer complications (SSE and bleeding events) than VKAs in the management of LVTs.

Compared with VKAs, DOACs result in significantly faster (only rivaroxaban) and safer resolution of left ventricular thrombosis.

Direct oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses.

We focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration.

Our computational investigation showed rivaroxaban (-4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (-5.97 kcal/mol) and dabigatran (-9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control.

Overall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.

There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice.

This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB.

The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

The methoxy substituent is prevalent in natural products and, consequently, is present in many natural product-derived drugs. It has also been installed in modern drug molecules with no remnant of natural product features because medicinal chemists have been taking advantage of the benefits that this small functional group can bestow on ligand-target binding, physicochemical properties, and ADME parameters. Herein, over 230 methoxy-containing small-molecule drugs, as well as several fluoromethoxy-containing drugs, are presented from the vantage point of the methoxy group. Biochemical mechanisms of action, medicinal chemistry SAR studies, and numerous X-ray cocrystal structures are analyzed to identify the precise role of the methoxy group for many of the drugs and drug classes. Although the methoxy substituent can be considered as the hybridization of a hydroxy and a methyl group, the combination of these functionalities often results in unique effects that can amount to more than the sum of the individual parts.

Cerebral Venous Thrombosis (CVT) poses a rare but life-threatening challenge, warranting meticulous treatment approaches. Traditional therapy involves Vitamin K Antagonists (VKAs), but Newer Oral Anticoagulants (NOACs) offer potential advantages. This study addresses a crucial knowledge gap in the Indian context, analyzing real-world data to guide CVT management decisions.

A single-center, ambispective cohort study included consecutive adult CVT patients. Data collection encompassed demographics, clinical data, imaging, and treatment details. Patients were categorized into VKA and NOAC groups. Outcomes measured recanalization status, functional outcomes, bleeding events, and adverse drug reactions.

Among 181 enrolled patients, NOAC-treated (Group B) individuals had significantly higher rates of complete recanalization (58.5% vs. 31.1%) with a similar incidence of adverse events and also displayed better functional outcomes at weeks 8 and 12 compared to VKA-treated (Group A) patients. Recurrent thromboembolic events were absent in both groups during follow-up.

This study highlights NOACs' potential advantages in CVT management, including improved functional outcomes, enhanced recanalization, and similar bleeding risk. Adverse events were milder with NOACs. While acknowledging limitations, these findings support NOACs as a promising alternative to VKAs, advancing CVT care and outcomes.

Cerebral venous sinus thrombosis (CVST) is a challenging condition to diagnose and treat due to its diverse range of clinical presentations. The incidence of CVST is increasing, and although diagnostic techniques have improved, the mainstay of treatment is heparin followed by vitamin K antagonist (VKA), warfarin has remained largely unchanged for the past three decades. However, new direct oral anticoagulants (NOACs) like dabigatran have been developed to address the limitations of VKA therapy. Magnetic resonance imaging (MRI) with magnetic resonance venography (MRV) is the current preferred diagnostic method for CVST due to its exceptional sensitivity and specificity. This prospective observational study was set out to investigate the efficacy and safety of dabigatran in treating cerebral venous sinus thrombosis. The study included 30 patients who reported regular intake of 150 mg dabigatran etexilate twice a day. Among the participants, headache was the most commonly reported symptom. The study found that patients treated with dabigatran experienced favorable outcomes, with all patients achieving re-canalization and reporting no major complications. These promising results suggest that dabigatran could be an effective treatment option for CVST cases. However, the study emphasizes the need for larger, multi-center studies to further validate these findings and improve the overall understanding of the condition and its treatment options.

Information regarding the safety and efficacy of specific direct oral anticoagulants (DOAC) in the treatment of cerebral sinus and venous thrombosis (CSVT) is scarce. Apixaban is one of the most frequently prescribed DOACs. Therefore, we aimed to compare the safety and efficacy of Apixaban with those of vitamin k antagonists (VKA) in patients with CSVT.

Prospective CSVT databases from seven academic medical centers were retrospectively analyzed. Patients treated with Apixaban were compared to those treated with VKA. Data on demographics, clinical presentations, risk factors, radiological and outcome parameters were studied.

Overall, 403 patients were included in the analysis. Of them, 48 (12%) were treated with Apixaban, and 355 (88%) were treated with VKA. Rates of coagulopathies were significantly higher in the VKA-treated patients but no other differences between the groups were found in baseline characteristics and underlying etiology. No significant differences were found between groups in efficacy or safety parameters including the rates of recanalization, favorable outcomes, one-year mortality, seizures, intracranial hemorrhage or CSVT recurrences.

Our data suggests that Apixaban may be safe and effective for patients with CSVT. These results should be tested in prospective randomized clinical studies.

The prescribing practice of newer oral anticoagulants (NOACs) has not been adequately studied in the Indian scenario.

We aimed to describe the prescribing practices of oral anticoagulants, the patient profile and medical comorbidities among patients admitted in a general medicine unit.

In this retrospective study of the 2742 patients prescribed vitamin- K antagonists (VKAs), during the study period, 150 cases were randomly taken for analysis to match the 105 NOACs cases. Their demographic details, clinical characteristics and treatment details were analyzed.

More than 95% of anticoagulants prescribed were VKAs. The prescription of anticoagulants was more common in men (median age 63 years) for prescription of NOACs and 52 years for VKAs. Dabigatran (60.9%) and warfarin (81.3%) were the most prescribed drugs in their respective classes. The most common indication was for cardiovascular diseases with atrial fibrillation (32%). Diabetes and hypertension were the most common comorbidities in patients prescribed oral anticoagulants with a larger proportion of patients with heart failure being prescribed VKAs ( P < 0.01). Patients in the NOACs group had a higher HAS-BLED high-risk score (33.3% vs. 17.3%; P = 0.002). Logistic regression analysis revealed that patients with co-morbidities of congestive heart failure were more likely to be prescribed VKAs while diabetics were more likely to receive NOACs.

VKAs were the most prescribed anticoagulants; congestive heart failure, diabetes, and hypertension were the commonest comorbidities; and atrial fibrillation was the commonest indication. Patients with a high HAS-BLED score were prescribed NOACs more often.

Factor XIIa (FXIIa) functions as a plasma serine protease within the contact activation pathway. Various animal models have indicated a substantial role for FXIIa in thromboembolic diseases. Interestingly, individuals and animals with FXII deficiency seem to maintain normal hemostasis. Consequently, inhibiting FXIIa could potentially offer a viable therapeutic approach for achieving effective and safer anticoagulation without the bleeding risks associated with the existing anticoagulants. Despite the potential, only a limited number of small molecule inhibitors targeting human FXIIa have been documented. Thus, we combined a small library of 32 triazole and triazole-like molecules to be evaluated for FXIIa inhibition by using a chromogenic substrate hydrolysis assay under physiological conditions. Initial screening at 200 μM involved 18 small molecules, revealing that 4 molecules inhibited FXIIa more than 20%. In addition to being the most potent inhibitor identified in the first round, inhibitor 8 also exhibited a substantial margin of selectivity against related serine proteases, including factors XIa, Xa, and IXa. However, the molecule also inhibited thrombin with a similar potency. It also prolonged the clotting time of human plasma, as was determined in the activated partial thromboplastin time and prothrombin time assays. Subsequent structure-activity relationship studies led to the identification of several inhibitors with submicromolar activity, among which inhibitor 22 appears to demonstrate significant selectivity not only over factors IXa, Xa, and XIa, but also over thrombin. In summary, this study introduces novel triazole-based small molecules, specifically compounds 8 and 22, identified as potent and selective inhibitors of human FXIIa. The aim is to advance these inhibitors for further development as anticoagulants to provide a more effective and safer approach to preventing and/or treating thromboembolic diseases.

Coumarins, widely abundant natural heterocyclic compounds, are extensively employed in creating various biologically and pharmacologically potent substances. The hybridization of heterocycles presents a key opportunity to craft innovative multicyclic compounds with enhanced biological activity. Fusing different heterocyclic rings with the coumarin structure presents an intriguing method for crafting fresh hybrid compounds possessing remarkable biological effects. In the pursuit of creating heterocyclic-fused coumarins, a wide range of annulated heterocyclic[g]coumarin composites has been introduced, displaying impressive biological potency. The influence of the linear attachment of heterocyclic rings to the coumarin structure on the biological performance of the resulting compounds has been investigated. This review centers on the synthetic methodologies, structural activity relationship investigation, and biological potentials of annulated heterocyclic[g]coumarin composites. We conducted searches across several databases, including Web of Science, Google Scholar, PubMed, and Scopus. After sieving, we ultimately identified and included 71 pertinent studies published between 2000 and the middle of 2023. This will provide valuable perspectives for medicinal chemists in the prospective design and synthesis of lead compounds with significant therapeutic effects, centered around heterocycle-fused coumarin frameworks.

Patients with non-valvular atrial fibrillation with diabetes face increased stroke and cardiovascular risks. This study compares factor Xa inhibitors and warfarin using data from randomized controlled trials (RCTs).

MEDLINE, Embase, and Cochrane CENTRAL databases were searched for RCTs comparing the risk of efficacy and safety of any factor Xa inhibitors with dose-adjusted warfarin by diabetes status. Incidence of stroke/systemic embolism, major bleeding, intracranial hemorrhage, ischemic stroke, all-cause mortality, risk of hemorrhagic stroke, and myocardial infarction were among the outcomes of interest. A generic inverse-weighted random-effects model was used to calculate hazard ratios (HRs) with 95 percent confidence intervals (CIs).

After applying exclusion criteria, four RCTs containing 19 818 patients were included in the analysis. Compared with warfarin, meta-analysis showed statistically significant reduction in incidence of stroke/systemic embolism (HR 0.80 [95% CI 0.69-0.92]; P=0.002), intracranial hemorrhage (HR 0.49 [95% CI 0.37-0.65]; P<0.001), and risk of hemorrhagic stroke (HR 0.37 [95% CI 0.20-0.66]; P=0.001) in patients on factor Xa inhibitors. However, there was no discernible difference between two treatment arms in incidence of major bleeding (HR 0.93 [95% CI 0.84-1.04]; P=0.19), ischemic stroke (risk ratio (RR) 0.90 [95% CI 0.73-1.12; P=0.34), myocardial infarction (RR 0.88 [95% CI 0.67-1.15]; P=0.35), and all-cause mortality (RR 0.89 [95% CI 0.79-1.01]; P=0.06).

Factor Xa inhibitors show a favorable balance between efficacy and safety compared with warfarin, which is consistent across a wide range of patients with atrial fibrillation known to be at high risk for both ischemic and bleeding events.

We compared the safety and efficacy of direct oral anticoagulants (DOACs) with those of warfarin in the long-term (≥6 months) treatment of cerebral venous thrombosis (CVT).

We searched electronic databases up to November 2023 to compare the use of DOACs and warfarin in CVT management. Modified Rankin scores (mRS), new intracranial hemorrhage, all-cause mortality, recurrence and nonrecanalisation events were used to assess outcome. RevMan v5.4 software and the Cochran-Mantel-Haenszel method were utilized to analyse data.

A total of 25 studies involving 2301 patients were identified as having treated CVT with either DOACs or warfarin. Good long-term mRS scores 0-2 (risk ratio [RR] = 1.01, 95% CI = 0.98-1.03; p = 0.61), new intracranial hemorrhage (RR = 1.00, 95% CI = 0.48-2.08; p = 0.99), all-cause mortality (RR = 1.00, 95% CI = 0.50-1.98; p = 0.99), nonrecanalisation (RR = 0.95, 95% CI = 0.77-1.18; p = 0.65) and recurrence venous thrombosis events (RR = 0.63, 95% CI = 0.33-1.22; p = 0.17) were similar between the two treatment arms. Subgroup analysis found recurrence of venous thrombosis was lower in the rivaroxaban group compared to warfarin (2.2% vs. 8.5%, RR = 0.33, 95% CI = 0.11-0.98; p = 0.05).

DOACs and warfarin provide comparable long-term safety and efficacy profiles. DOACs may be preferred over warfarin due to their ease of clinical management.

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.

Orthopedic surgeries are associated with high-risk of thromboembolism which occurs in 40% to 60% of orthopedic patients in the absence of thromboprophylaxis. Conventionally heparin anticoagulants were used for thromboprophylaxis and currently direct oral anticoagulants (DOACs) are widely used due to their minimal complexity. Anticoagulant use carries bleeding risk and requires optimal laboratory monitoring through conventional thrombin-based assays, anti-Xa assay, anti-IIa assay and contemporary ecarin chromogenic assay (ECA) and rotational thromboelastometry. Monitoring requires multiple hospital visits and hence, the development of point-of-care assays is gaining momentum. Also, a thorough risk assessment model (RAM) is necessary for successful anticoagulant therapy since it enables personalized approach for better thromboprophylaxis outcomes. Despite welcoming changes, lack of guideline consensus, population-based thromboprophylaxis, deficiencies in risk stratification and non-adherence are still a concern. Stronger clinical and process support system with uniform guidelines approaches and patient-specific RAM can aid in the successful implementation of anticoagulant therapy.

This study aimed to explore the roles of duration and burden of atrial high-rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation.

Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA2 DS2 -VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time-dependent covariates was conducted.

A total of 220 patients with AHRE were enrolled. The average follow-up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p = .024), high CHA2 DS2 -VASc score (≥ 2) (p = .021), long mean AHRE burden (p = .011), long maximal AHRE burden (p = .015), long AHRE duration lasting≥48 h (p = .001) or 24 h (p = .001) or 12 h (p = .005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22-55.12; p = .030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p = .927).

The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA2 DS2 -VASc score (≥2).

Non-VKA oral anticoagulants (NOACs) prescription is increasing in adults with congenital heart disease (ACHD). However, data on efficacy and safety in ACHD is unclear, particularly in severe CHD. The study aimed to review the safety and efficacy of NOACs in ACHD.

Retrospective evaluation of ACHD patients started on NOACs from 2014 to 2020, with the primary endpoints of bleeding or thromboembolic events (TE). CHA2DS2-VASc and HAS-BLED scores were calculated, mortality was assessed, and risk factors for bleeding were identified.

A total of 93 patients were included, the mean age was 52 ± 15 years, 58% were female, 55.9% had moderate CHD, and 23.7% had severe CHD (3.2% Fontan). Most (66%) had a CHA2DS2-VASc score ≥ 2 and 82% HAS-BLED ≤ 2. In a median follow-up of 41 (IQR 21) months (400.4 patient-years), there were TE in two patients. The annual risk for TE was 0.49%/patient/year. The cardiovascular mortality was 2% and all-cause mortality 5%; there were no fatal TE or bleeding events. Minor (n = 6, 6.5%) and major (n = 3, 3.2%) bleeding events were observed, a median of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. Renal disease (HR 14.6 [95% CI 1.23-73.6], p = 0.033) and the HAS-BLED score were predictors of major (adjusted HR 6.97 [95% CI 1.69-28.78], p = 0.007) and minor (adjusted HR 3.80 [95% CI 1.48-9.78], p = 0.006) bleeding complications.

In this real-life cohort of selected ACHD, the use of NOACs was safe and effective, with a low incidence of bleeding events.

(1) Background: Direct oral anticoagulants (DOACs) require monitoring in some critical clinical situations. The specific tests for DOAC monitoring are not yet available in all labs. The aim of this study was to evaluate if a unique, more widespread heparin-calibrated anti-Xa assay could be suitable to estimate the concentrations of apixaban and rivaroxaban in order to establish an algorithm helping our clinicians in their therapeutic decision for patients treated with DOACs in emergencies. (2) Methods: A first retrospective part allowed us to determine of a conversion factor between the measured DOAC concentration and the deducted anti-Xa heparin activity based on optic density. During the second prospective part, both DOAC concentration (ng/mL) and anti-Xa activity heparin (UI/mL) were measured on the same sample, and the previously determined conversion factor was applied to each UI/mL value. We then compared the calculated and measured DOAC concentration values. (3) Results: The analysis of the derivation cohort confirmed a good correlation, especially between the anti-Xa heparin activity and the apixaban concentrations (r = 0.97). Additionally, we determined heparin-calibrated anti-Xa assay cut-offs for invasive procedures at 0.3 UI/mL and for intravenous thrombolysis at 0.51 UI/mL using ROC curves with a sensitivity at 98% and specificity at 95% for 0.3 UI/mL and a sensitivity at 97.7% and specificity at 88.2% for the cut-off of 0.51 UI/mL. In the validation cohort, we confirmed the agreement between measured and calculated DOAC concentrations for the low values, especially around cut-offs with an excellent negative predictive value for 0.51 UI/mL (94% for apixaban and 100% for rivaroxaban) and a good negative predictive value for 0.3 UI/mL (83.3% for apixaban and 85.7% for rivaroxaban). (4) Conclusions: Our results confirm that it is possible to correctly predict or exclude the presence of apixaban/rivaroxaban in emergency situations when specific tests are not readily available.

Direct oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking.

Prospective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA.

Out of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed.

Our data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

The real-world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA-AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA-AF population.

One-year data from 1887 Korean ETNA-AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA-AF registries.

Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non-recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (<65 years), youngest-old (65-74 years) and middle-old/oldest-old (≥75 years) groups were 21.4%, 40.2%, and 38.4%, respectively. Incidence of major or clinically relevant nonmajor bleeding was similar within dose (0.57%-1.71%) and age subgroups (1.26%-1.63%). Incidence of net clinical outcome, a composite of stroke, systemic embolic event, major bleeding, and all-cause mortality, was also comparable among dose subgroups (1.14%-3.10%) and age subgroups (2.28%-2.78%). The percentage of Korean patients receiving non-recommended 30 mg (19.8%) was over twice that of the European population (8.4%). However, the clinical outcomes were generally similar among different populations included in the ETNA-AF study.

The outcomes in the Korean ETNA-AF population are like those in the global ETNA-AF population, with overall low event rates of stroke, major bleeding and all-cause mortality across age and dose subgroups. Edoxaban can be used effectively and safely in specific populations of Korean AF patients, including the elderly.

Valvular heart disease is a common disease often necessitating valve replacement. Mechanical heart valves (MHVs) are often used in younger patients because of their longer durability. Their main disadvantage is the need for lifelong anticoagulation. Warfarin is considered a standard treatment, but it is far from perfect. Direct oral anticoagulants (DOACs) are a new and more patient-friendly alternative to warfarin when anticoagulation is required, but have not yet been approved for the indication of mechanical valves.

A literature search of Pubmed, Embase, Web of Science (Core Collection), and Cochrane Library (from inception to May 2023) was performed using a search string that was well defined and not modified during the study. An extensive overview of the search terms used in each database can be found in the Appendix. Only prospective clinical trials were included in this review. A total of 10 publications were included in this review.

This systematic review summarizes the different types of DOACs and their possible use in the anticoagulation of mechanical valves. We aim to propose future directions in anticoagulation research for mechanical valves.

DOAC use in MHVs has been halted due to the failure of both dabigatran and apixaban in two major clinical trials. However, rivaroxaban was successful in two small clinical trials. Ample research is still needed to explore new valve designs as well as new anticoagulation targets.

Cardioembolic stroke (CS) has emerged as a leading cause of ischaemic stroke (IS); distinguished by thrombi embolising to the brain from cardiac origins; most often from the left atrial appendage (LAA). Contemporary therapeutic options are largely dependent on systemic anticoagulation as a blanket preventative strategy, yet this does not represent a nuanced or personalised solution. Contraindications to systemic anticoagulation create significant unmedicated and high-risk cohorts, leaving these patients at risk of significant morbidity and mortality. Atrial appendage occlusion devices are increasingly used to mitigate stroke risk from thrombi emerging from the LAA in patients ineligible for oral anticoagulants (OACs). Their use, however, is not without risk or significant cost, and does not address the underlying aetiology of thrombosis and CS. Viral vector-based gene therapy has emerged as a novel strategy to target a spectrum of haemostatic disorders, achieving success through the adeno-associated virus (AAV) based therapy of haemophilia. Yet, thrombotic disorders, such as CS, have had limited exploration within the realm of AAV gene therapy approaches-presenting a gap in the literature and an opportunity for further research. Gene therapy has the potential to directly address the cause of CS by localised targeting of the molecular remodelling that serves to promote thrombosis.

Nanostructured lipid carriers (NLCs) have been proven to significantly improve the bioavailability and efficacy of many drugs; however, they still have many limitations. These limitations could hinder their potential for enhancing the bioavailability of poorly water-soluble drugs and, therefore, require further amendments. From this perspective, we have investigated how the chitosanization and PEGylation of NLCs affected their ability to function as a delivery system for apixaban (APX). These surface modifications could enhance the ability of NLCs to improve the bioavailability and pharmacodynamic activity of the loaded drug. In vitro and in vivo studies were carried out to examine APX-loaded NLCs, chitosan-modified NLCs, and PEGylated NLCs. The three nanoarchitectures displayed a Higuchi-diffusion release pattern in vitro, in addition to having their vesicular outline proven via electron microscopy. PEGylated and chitosanized NLCs retained good stability over 3 months, versus the nonPEGylated and nonchitosanized NLCs. Interestingly, APX-loaded chitosan-modified NLCs displayed better stability than the APX-loaded PEGylated NLCs, in terms of mean vesicle size after 90 days. On the other hand, the absorption profile of APX (AUC_0-inf) in rats pretreated with APX-loaded PEGylated NLCs (108.59 µg·mL^-1·h^-1) was significantly higher than the AUC_0-inf of APX in rats pretreated with APX-loaded chitosan-modified NLCs (93.397 µg·mL^-1·h^-1), and both were also significantly higher than AUC_0-inf of APX-Loaded NLCs (55.435 µg·mL^-1·h^-1). Chitosan-coated NLCs enhanced APX anticoagulant activity with increased prothrombin time and activated partial thromboplastin time by 1.6- and 1.55-folds, respectively, compared to unmodified NLCs, and by 1.23- and 1.37-folds, respectively, compared to PEGylated NLCs. The PEGylation and chitosanization of NLCs enhanced the bioavailability and anticoagulant activity of APX over the nonmodified NLCs; this highlighted the importance of both approaches.

Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

Data regarding adherence and minor bleeding on direct oral anticoagulants in everyday life are still sparse. Inclusion criteria: treatment initiated with dabigatran, rivaroxaban or apixaban in non-valvular atrial fibrillation patients from a center in northern Sweden between 2011 and 2019 (n = 668). Exclusion criteria: cognitive impairment, dose dispensing, need of interpreter or hospital admission (n = 67). By a telephone interview adherence was measured in 569 patients (response rate 94.8%) using the 8-item Morisky medication adherence scale and minor bleeding was asked for. CHA₂DS₂-VASc and HAS-BLED scores were collected from medical records. The number (n), mean age, mean treatment duration, mean (points) CHA₂DS₂-VASc and HAS-BLED scores was with dabigatran (n = 175, 73.3 years, 17.8 months, 3.6 p and 2.2 p), rivaroxaban (n = 198, 73.7 years, 21months, 3.8 p and 2.1 p) and apixaban (n = 196, 72.7 years, 15.2 months, 3.4 p and 2.1 p). Adherence was high for dabigatran, rivaroxaban and apixaban in 54%, 76% and 53%; intermediate in 37%, 20% and 37% or low in 9%, 4% and 10% respectively. High adherence (Morisky score 8) distinguished rivaroxaban (p < 0.0001) and in patients with CHA₂DS₂-VASc ≥ 4 p, (p < 0.0001). Patients on rivaroxaban/apixaban reported more minor bleedings (37% / 28%) compared to dabigatran (13%), (p < 0.001). Only 61% of the patients followed prescription. Adherence to rivaroxaban was significantly better, maybe due to the once daily dosing regimen, and furthermore among patients with higher risk for stroke. Minor bleedings were less common in the dabigatran group. The impact of minor bleedings on adherence and a possible relationship to clinical outcomes need to be further studied.

As direct-acting oral anticoagulants (DOACs) have short half-lives of around 12 h, even a short gap in DOAC therapy may diminish anticoagulation effects, increasing risks of adverse clinical outcomes. We aimed to evaluate clinical consequences of a gap in DOAC therapy with atrial fibrillation (AF) and to identify its potential predictors.

In this retrospective cohort study, we included DOAC users aged over 65 years with AF from the 2018 Korean nationwide claims database. We defined a gap in DOAC therapy as no claim for a DOAC one or more days after the due date of a refill prescription. We used a time-varying-analysis method. The primary outcome was a composite of death and thrombotic events including ischemic stroke/transient ischemic attack or systemic embolism. Potential predictors of a gap included sociodemographic and clinical factors.

Among 11,042 DOAC users, 4857 (44.0 %) patients had at least one gap. Standard national health insurance, non-metropolitan locations of medical institutions, history of liver disease, chronic obstructive pulmonary disease, cancer, or dementia, and use of diuretics or non-oral agents were associated with increased risks of a gap. In contrast, history of hypertension, ischemic heart disease, or dyslipidemia were associated with a decreased risk of a gap. A short gap in DOAC therapy was significantly associated with a higher risk of the primary outcome compared to no gap (hazard ratio 4.04, 95 % confidence interval 2.95-5.52). The predictors could be utilized to identify at-risk patients to provide additional support to prevent a gap.

Screening for Atrial Fibrillation (AF) is recommended for people aged above 65 years. Screening for AF in asymptomatic individuals can be beneficial by enabling earlier diagnosis and the commencement of interventions to reduce the risk of early events, thus improving patient outcomes. This study systematically reviews the literature about the cost-effectiveness of various screening methods for previously undiagnosed AF.

Four databases were searched to identify articles that are cost-effectiveness studies conducted on screening for AF published from January 2000 to August 2022. The Consolidated Health Economic Evaluation Reporting Standards 2022 checklist was used to assess the quality of the selected studies. A previously published approach was used to assess the usefulness of each study for health policy makers.

The database search yielded 799 results, with 26 articles meeting the inclusion criteria. Articles were categorised into four subgroups: (i) population screening, (ii) opportunistic screening, (iii) targeted, and (iv) mixed methods of screening. Most of the studies screened adults ≥65 years of age. Most studies were performed from a 'health care payer perspective' and almost all studies used 'not screening' as a comparator. Almost all screening methods assessed were found to be cost-effective in comparison to 'not screening'. The reporting quality varied between 58% to 89%. The majority of the studies were found to be of limited usefulness for health policy makers, as none of the studies made any clear statements about policy change or implementation direction.

All approaches of AF screening were found to be cost-effective compared with no screening, while opportunistic screening was found to be the optimal approach in some studies. However, screening for AF in asymptomatic individuals is context specific and likely to be cost-effective depending on the population screened, screening approach, frequency, and the duration of screening.

Limited real-world data are available on the survival of patients treated with vitamin K antagonists (VKAs) versus with direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (AF). In this nationwide registry, we analyzed the mortality risk of patients with nonvalvular AF taking DOACs versus VKAs, with a special attention to the early treatment period.

The Hungarian National Health Insurance Fund (NHIF) database was searched to identify patients treated with VKA or DOAC as a thromboembolic prophylaxis for nonvalvular AF between 2011 and 2016. The overall and the early (0-3, 4-6, and 7-12 months) mortality risks with the 2 types of anticoagulation were compared. A total of 144,394 patients with AF treated with either a VKA (n = 129,925) or a DOAC (n = 14,469) were enrolled.

A 28% improvement in 3-year survival with DOAC treatment compared with VKA treatment was shown. Mortality reduction with DOACs was consistent across different subgroups. However, younger patients (30-59 years old) initiated on DOAC therapy had the greatest RRR (53%) in mortality. Furthermore, DOAC treatment also yielded a benefit of greater magnitude (HR = 0.55; 95% CI, 0.40-0.77, P = 0.001) in the lower (0-1) CHA₂DS₂-VASc score segment and in those with fewer (0-1) bleeding risk factors (HR = 0.50, CI 0.34-0.73, P = 0.001). The RRR in mortality with DOACs was 33% within the first 3 months, and 6% in the second year.

Thromboembolic prophylaxis with DOACs in this study yielded significantly lower mortality compared with VKA treatment in patients with nonvalvular AF. The largest benefit was shown in the early period after treatment initiation, as well as in younger patients, those with a lower CHA₂DS₂-VASc score, and those with fewer bleeding risk factors.

Patients at increased risk of bleeding and recurrent VTE who develop venous thromboembolism (VTE) present challenges for clinical management. This study evaluated the effectiveness and safety of apixaban vs warfarin in patients with VTE who have risk factors for bleeding or recurrences.

Adult patients with VTE initiating apixaban or warfarin were identified from five claims databases. Stabilized inverse probability treatment weighting (IPTW) was used to balance characteristics between cohorts for the main analysis. Subgroup interaction analyses were conducted to evaluate treatment effects among patients with and without each of the conditions that increased the risk of bleeding (thrombocytopenia and history of bleed) or recurrent VTE (thrombophilia, chronic liver disease, and immune-mediated disorders).

A total of 94,333 warfarin and 60,786 apixaban patients with VTE met selection criteria. After IPTW, all patient characteristics were balanced between cohorts. Apixaban (vs warfarin) patients were at lower risk of recurrent VTE (HR [95% confidence interval (CI) 0.72 [0.67-0.78]), major bleeding (MB) (HR [95% CI] 0.70 [0.64-0.76]), and clinically relevant non-major (CRNM) bleeding (HR [95% CI] 0.83 [0.80-0.86]). Subgroup analyses showed generally consistent findings with the overall analysis. For most subgroup analyses, there were no significant interactions between treatment and subgroup strata on VTE, MB and CRNM bleeding.

Patients with prescription fills for apixaban had lower risk of recurrent VTE, MB, and CRNM bleeding compared with warfarin patients. Treatment effects of apixaban vs warfarin were generally consistent across subgroups of patients at increased risk of bleeding/recurrences.

Despite their effectiveness and ease of use, medication errors have been reported to be highly prevalent with direct-acting oral anticoagulants (DOAC).

The aim of this study was to explore views and experiences of pharmacists on contributory factors and mitigation strategies around medication errors in relation to DOAC.

This study used a qualitative design. Semi-structured interviews were conducted with hospital pharmacists in Saudi Arabia. The interview topic guide was developed based on previous literature and Reason's Accident Causation Model. All interviews were transcribed verbatim and MAXQDA Analytics Pro 2020 was used to thematically analyse the data (VERBI Software).

Twenty-three participants representing a range of experiences participated. The analysis recognised three major themes: (a) enablers and barriers faced by pharmacists in promoting safe utilisation of DOAC, such as opportunities to conduct risk assessments and offer patient counselling (b) factors related to other healthcare professionals and patients, such as opportunities for effective collaborations and patient health literacy; and (c) effective strategies to promote DOAC safety such as empowering the role of pharmacists, patient education, opportunities for risk assessments, multidisciplinary working and enforcement of clinical guidelines and enhanced roles of pharmacists.

Pharmacists believed that enhanced education of healthcare professionals and patients, development and implementation of clinical guidelines, improvement of incident reporting systems, and multidisciplinary team working could be effective strategies to reduce DOAC-related errors. In addition, future research should utilise multifaceted interventions to reduce error prevalence.

Oral anticoagulants (OACs) are commonly used to reduce the risk of venous thromboembolism and the risk of stroke in patients with atrial fibrillation. Endorsed by the American Heart Association, American College of Cardiology, and the European Society of Cardiology, direct oral anticoagulants (DOACs) have displaced warfarin as the OAC of choice for both conditions, due to improved safety profiles, fewer drug-drug and drug-diet interactions, and lack of monitoring requirements. Despite their widespread use and improved safety over warfarin, DOAC-related bleeding remains a major concern for patients. DOACs have stable pharmacokinetics and pharmacodynamics; however, variability in DOAC response is common and may be attributed to numerous factors, including patient-specific factors, concomitant medications, comorbid conditions, and genetics. Although DOAC randomized controlled trials included patients of varying ages and levels of kidney function, they failed to include patients of diverse ancestries. Additionally, current evidence to support DOAC pharmacogenetic associations have primarily been derived from European and Asian individuals. Given differences in genotype frequencies and disease burden among patients of different biogeographic groups, future research must engage diverse populations to assess and quantify the impact of predictors on DOAC response. Current under-representation of patients from diverse racial groups does not allow for proper generalization of the influence of clinical and genetic factors in relation to DOAC variability. Herein, we discuss factors affecting DOAC response, such as age, sex, weight, kidney function, drug interactions, and pharmacogenetics, while offering a new perspective on the need for further research including frequently excluded groups.

Aim    To perform a systematic review and meta-analysis of efficacy and safety of direct oral anticoagulants (DOAC) as compared to vitamin K antagonists (VKA) in the treatment of left ventricular (LV) thrombosis.Material and methods    A search was performed in PubMed and Google Scholar for studies that compared DOAC and VKA in the treatment of LV thrombosis with respect of thromboembolic events, hemorrhagic complications, and thrombus resolution. The effect was evaluated with the odds ratio (OR) that was computed using a fixed effects model.Results    For these systematic review and meta-analysis, 19 studies were selected, including 2 randomized and 17 cohort studies. The articles included into these systematic review and meta-analysis, were published from 2018 through 2021. In total, 2970 patients (mean age, 58.8 лет; 1879 (61.2 %) men) with LV thrombus were included into the meta-analysis. Mean follow-up duration was 17.9 months. The meta-analysis showed no significant difference between DOAC and VKA in the incidence of the study outcomes: thromboembolic events (OR, 0.86; 95 % CI: 0.67-1.10; р=0.22), hemorrhagic complications (OR, 0.77; 95 % CI: 0.55-1.07; р=0.12), thrombus resolution (OR, 0.96; 95 % CI: 0.76-1.22; р=0.77). In a subgroup analysis, rivaroxaban compared to VKA significantly (79%) reduced the risk of thromboembolic complications (OR, 0.21; 95 % CI: 0.05-0.83; р=0.03) with no significant differences in hemorrhagic events (OR, 0.60; 95 % CI: 0.21-1.71; р=0.34) or thrombus resolution (OR, 1.44; 95 % CI: 0.83-1.31; р=0.20). The apixaban treatment group had significantly more (4.88 times) cases of thrombus resolution than the VKA treatment group (OR, 4.88; 95 % CI: 1.37-17.30; р=0.01); for apixaban, data on hemorrhagic and thromboembolic complications were not available.Conclusions    The therapeutic efficacy and side effects of the DOAC treatment for LV thrombosis were similar to those of VKA with respect of thromboembolic events, hemorrhage, and thrombus resolution.

The management of patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) requires appropriate antithrombotic regimens for stroke prevention and in-stent thrombosis. Current practice recommendations are largely based on consensus options as there is limited evidence from randomized clinical trials. Hence, by surveying a group of cardiologists across India, we sought to better understand the current practice patterns of using oral anticoagulants (vitamin K antagonist, VKA or non-vitamin K antagonist oral anticoagulant, NOAC) and antiplatelet therapy in those patients in India.

A cross-sectional questionnaire-based survey was conducted across India to better understand the clinical practices in AF management.

A total of 151 cardiologists participated in this survey. The most commonly prescribed combination therapy in patients with AF and ACS/undergoing PCI was triple therapy (NOAC + dual antiplatelet [aspirin and P2Y12 inhibitor]) (54.30%) followed by NOAC + single antiplatelet (33.11%). Only 11.26% of cardiologists prescribed VKA + dual antiplatelet therapy. Among anticoagulants, cardiologists prescribed NOACs to 66.11% of patients and VKAs to 25.54% of patients. Among P2Y12 inhibitors, ticagrelor (50.99%) and clopidogrel (47.02%) were the most preferred medication. The physician reported patient adherence rates to NOACs were higher compared to VKAs. Around 41.06% of cardiologists reportedly changed antiplatelet therapy for patients from dual antiplatelet to single antiplatelet therapy in three months; 36.42%, in one month; and 19.21% in six months after PCI. Around 61.59% of cardiologists stopped prescribing antiplatelet therapy for patients by one year.

Our survey demonstrated that the majority of cardiologists used triple therapy (NOAC + dual antiplatelet), followed by NOAC + single antiplatelet for managing patients with AF and ACS or undergoing PCI in line with the available guidelines.

Objective-Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods-Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results-During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS_4-5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS_1-3) after 12 months. Conclusions-Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.

Thromboembolism (TE) is a common and serious complication of nephrotic syndrome (NS). NS is associated with hypercoagulability, which may be induced by changes in coagulation, anticoagulant, and fibrinolytic factors. Moreover, accumulating evidence supports the hypothesis that the complex interactions between genetic and acquired risk factors in TE should be considered and that genetic susceptibility should not be ignored. Extracellular vesicles (EVs) also play unique roles. Further research on EVs may provide new insights into the discovery and treatment of TE associated with NS. The occurrence of NS accompanied by TE may be associated with various risk factors. Preventive anticoagulant therapy can not only reduce the risk of TE in patients but also aggravate the risk of bleeding. Heparin and vitamin K antagonists (VKAs), traditional anticoagulant drugs, have been extensively applied in the prevention and treatment of thromboembolic diseases, and emerging direct oral anticoagulants (DOACs) also provide an alternative choice. Owing to the particularity of NS, the safe application of DOACs still needs to be addressed. This review aimed to comprehensively describe the pathophysiology of TE in NS, as well as analyze the associated risk factors, the opportunity for preventive anticoagulation, and current anticoagulant information.

Rheumatic heart disease (RHD) remains a major healthcare problem. Atrial fibrillation (AF) is the commonest sustained arrhythmia in RHD, leading to major complications and morbidity in a young population. Currently, anticoagulation with vitamin K antagonists (VKA) is the mainstay of therapy for the prevention of thromboembolic adverse events. However, effective use of VKA remains challenging, especially in developing countries, showing a need for alternatives. Novel oral anticoagulants (NOACs), including rivaroxaban, could form a safe and effective alternative to fulfil a major unmet need in RHD patients with AF. However, until recently, no data was available for the use rivaroxaban in patients with rheumatic heart disease associated AF. Study and Results: The INVICTUS trial was conducted to assess efficacy and safety of once-daily rivaroxaban compared with a dose-adjusted VKA for the prevention of cardiovascular events in patients with RHD-associated AF. A total of 4531 patients (age: 50.5 ± 14.6 years) were followed for 3.1 ± 1.2 years in which 560/2292 patients in the rivaroxaban group and 446/2273 in the VKA group had a primary-outcome adverse event. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the VKA group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P <0.001). A higher incidence of death occurred in the rivaroxaban group than in the VKA group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted.

The INVICTUS trial shows that Rivaroxaban is inferior to Vitamin K-antagonists in patients with RHD associated AF as VKA therapy led to a lower rate of ischemic and lower mortality due to vascular causes, without significantly increasing the rate of major bleeding. The results support current guidelines, which recommend vitamin K antagonist therapy for the prevention of stroke in patients with RHD associated AF.