Vitamin K Antagonists Research Articles

Anticoagulation approach in morbid obesity: a comprehensive review on venous thromboembolism management

Obesity is a recognized risk factor for venous thromboembolism (VTE), associated with distinct challenges in managing anticoagulation therapy. There is still limited evidence regarding the impact of extreme body weight on the pharmacokinetics, pharmacodynamics, efficacy, and safety of various anticoagulant medications. To our knowledge, this is the first comprehensive review to address both prophylactic and therapeutic anticoagulant dosages specifically for managing VTE in patients with a body mass index (BMI) ≥40 kg/m2 or weight ≥120 kg. Our aim was to synthesize the findings of relevant studies alongside the latest recommendations on anticoagulation in this unique population. We gathered and analyzed data on all classes of anticoagulants available for VTE management, including vitamin K antagonists (VKAs), unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, and direct oral anticoagulants (DOACs), offering insights into their efficacy and safety profiles. Additionally, we explored special subpopulations of morbidly obese patients, such as those with cancer, renal dysfunction, or those undergoing bariatric surgery, recognizing the nuanced therapeutic challenges they present. The current evidence for anticoagulant therapy in morbidly obese patients with VTE is evidently insufficient, underscoring the need for a tailored approach and meticulous monitoring to achieve an optimal therapeutic balance.

Prescription Medication Use and Expenditure of Atrial Fibrillation in the United States.

To study the national trends of anticoagulants, antiarrhythmic drugs (AAD), and expenditures in civilian non-institutionalized AF population. The Medical Expenditure Panel Survey (MEPS) was queried from January 2016 to December 2021 to identify adults (age ≥ 18 years) with a diagnosis of AF utilizing ICD-10-CM code "I48". Prevalence of anticoagulants, AAD, and its expenditure and AF expenditure across clinical settings in the United States were estimated. The predictors of anticoagulant use were identified utilizing multivariate logistic regression analysis. A total of 17.3 million AF adults were identified, of which 46.5% were female, 89.6% were White, and ∼70% were middle/high-income with prevalent comorbidities of hypertension (75.3%) and coronary heart disease (30%). The mean CHA2DS2 VASc score was 3.2, and 40% had a score of ≥4. In the US, an average of $26,103 (2021 inflation-adjusted) was spent per year per adult with AF for health-related expenditures. The prevalence of direct oral anticoagulants (DOAC) and Class I AAD use has increased; in contrast, vitamin K antagonists (VKA) use has declined. DOAC-related per-person annual expenses increased from $849 in 2016 to $1,929 in 2021. In those with a CHA2DS2 VASc score of ≥2, female sex and the presence of coronary heart disease were associated with a lower likelihood of anticoagulant use. AF is a costly condition in which prescription medication use, like DOACs and class III AADs, are significant contributors.

Drug-drug interactions in critically ill patients

Critically ill patients are at high risk of adverse drug-drug interactions. Pharmacodynamic drug-drug interaction may cause organ damage. Pharmacokinetic interactions are usually caused by inhibition or induction of enzymes of drug metabolism such as cytochromeP-450 isoenzymes or transporter proteins such as P‑glycoprotein. Inhibitors of such molecules can cause toxic levels of the corresponding substrates, while inducers might produce subtherapeutic concentrations. Amiodarone, macrolides, antifungal azoles, direct-acting anticoagulants, vitaminK antagonists, immunosuppressants, rifampicin, and some central nervous system (CNS)-active substances are frequently involved in drug-drug interactions. Sound risk and benefit assessment of the applied medication, therapeutic drug monitoring, the use of electronic alert systems and databases along with clinical evaluation will contribute to avoiding adverse drug-drug interactions.

Warfarin and heparin monitoring in antiphospholipid syndrome.

Anticoagulation is central to the management of antiphospholipid syndrome (APS), an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL; ie, 1 or more of lupus anticoagulant [LA], anticardiolipin, anti-beta-2- glycoprotein I, IgG, or IgM antibodies). The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Accurate assessment of anticoagulation intensity underpins optimal anticoagulant dosing for thrombus treatment or primary/secondary prevention. In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between LA and the thromboplastin reagent used in the INR determination. In this review, we summarize the use of warfarin/VKA in patients with APS, along with venous and point-of-care INR monitoring. We also discuss the role and monitoring of LMWH/UFH, including in the anticoagulant refractory setting and during pregnancy.

JTH in Clinic – Choosing the optimal oral anticoagulant for stroke prevention in atrial fibrillation: direct oral anticoagulants vs. vitamin K antagonists

Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) for stroke prevention in many patients with atrial fibrillation (AF) but VKAs may still be preferred in some situations. We use a case-based approach to present the evidence for the possible use of a VKA in preference to a DOAC in patients with AF and rheumatic mitral stenosis, high body mass index, frailty and with breakthrough stroke despite being prescribed a DOAC.

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study.

This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB). Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE). Patient characteristics were balanced using propensity score matching. A total of 314,184 patients were identified with 162,150 (51.5%) in the apixaban cohort, 88,427 (28.1%) in the rivaroxaban cohort, 16,465 (5.2%) in the dabigatran cohort, and 47,142 (15.0%) in the VKA cohort (mean age 79.0 years, standard deviation 10.5; 51.0% female). A total of 45,124 apixaban-VKAs, 38,737 rivaroxaban-VKAs, 16,415 dabigatran-VKAs, 88,414 apixaban-rivaroxaban, 16,464 apixaban-dabigatran, and 16,459 rivaroxaban-dabigatran pairs were retained after propensity score matching. Apixaban had lower risk of MB versus dabigatran (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83) and rivaroxaban (HR, 0.63; 95% CI, 0.59-0.66). Apixaban had lower risk of GIB versus dabigatran (HR, 0.46; 95% CI, 0.37-0.56) and rivaroxaban (HR, 0.54; 95% CI, 0.49-0.59). Risk of GIB was similar with dabigatran versus rivaroxaban (HR, 1.05; 95% CI, 0.89-1.24). Apixaban had lower risk of stroke/SE versus rivaroxaban (HR, 0.90; 95% CI, 0.84-0.96), while risk was similar versus dabigatran (HR, 1.1; 95% CI, 0.9-1.3). All DOACs had lower risk of MB and stroke/SE versus VKAs (p<0.001 for all). DOACs had improved safety and effectiveness from bleeding and stroke/SE, respectively, versus VKAs among patients with NVAF at high risk for GIB. Apixaban was associated with lower MB and GIB risk versus other DOACs. For stroke/SE, apixaban was associated with reduced risk versus rivaroxaban and similar risk versus dabigatran.

Comparative Investigation of Thromboelastometry and Thrombin Generation for Patients Receiving Direct Oral Anticoagulants or Vitamin K Antagonists.

Background. Alterations induced by direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) to thromboelastometry and thrombin generation are not well defined. We performed a simultaneous investigation of thromboelastometry and thrombin generation for patients who were chronically anticoagulated with DOACs or VKAs. Methods. A total of 131 patients on DOACs [apixaban (n = 37), rivaroxaban (n = 34), dabigatran (n = 30), edoxaban (n = 30)] and 33 on VKAs were analyzed. Whole blood was analyzed for thromboelastometry and plasma was analyzed for thrombin generation. Results. While the thromboelastometry clotting time (CT) was responsive to the hypocoagulability induced by DOACs or VKAs, clot formation time and maximal clot formation were not. Cumulatively, the parameters denoting the velocity of thrombin generation (lag time, time-to-peak) were relatively less responsive to the hypocoagulability induced by VKAs than DOACs. Conversely, the parameters denoting the quantity of thrombin generation [peak-thrombin and the endogenous thrombin potential (ETP)] were more responsive to the hypocoagulability induced by VKAs than DOACs. Apixaban showed relatively small differences (peak vs. trough) in the plasma concentration and a relatively small (peak vs. trough) difference of hypocoagulability when assessed by the CT or the ETP. The CT and the ETP were strongly correlated with DOAC concentrations or with the VKA-INR. Conclusions. DOACs and VKAs altered thromboelastometry and thrombin generation to an extent that probably reflects the mode of action of these drugs and may also have practical implications for patients' management. Apixaban showed a small difference of hypocoagulability (peak vs. trough), suggesting a more stable anticoagulation over the daily course of treatment. Based on the correlations of the CT or the ETP vs. the DOAC concentrations, we estimated that critical values of the CT or the ETP would correspond to DOAC concentrations of 400 or 20 ng/mL. Whenever dedicated tests for DOAC concentrations are not available, the CT or the ETP can be used as surrogates to evaluate the level of anticoagulation induced by DOACs.

Bleeding Risk of Anticoagulation Reversal Strategies Before Heart Transplantation: A Retrospective Comparative Cohort Study.

Heart transplantation (HT) poses high bleeding risks, especially for patients on anticoagulation. This study evaluates the use of idarucizumab for dabigatran (DBG) reversal compared to vitamin K antagonist (VKA) strategies in HT. A retrospective analysis of HT patients from January 2018 to December 2022, excluding those requiring ECMO immediately before or after surgery, was conducted. Outcomes included transfusion needs, re-surgery due to bleeding, ICU stay lengths, and 30-day survival. A cost analysis compared the direct expenses of each strategy. Among 34 patients, 20 were on DBG and 14 on VKAs or not anticoagulated. Idarucizumab significantly reduced the number of patients requiring transfusion (p = 0.034) and ICU stay lengths (p = 0.014), with no significant impact on re-surgery rates (p = 0.259) or survival (p = 0.955). Despite higher initial costs, overall expenses for idarucizumab were comparable to VKA reversal due to reduced transfusion needs and shorter ICU stays. Idarucizumab offers a viable and potentially cost-neutral anticoagulation reversal option for HT patients on DBG, presenting an alternative to VKA strategies. However, due to the retrospective nature of the study and the small sample size, further prospective studies are needed to confirm these findings.

Abstract 4138813: The Use of Direct Oral Anticoagulants for Valvular Atrial Fibrillation in Central Australia

Background: In developed countries, valvular atrial fibrillation (vAF) in the setting of rheumatic heart disease (RHD) disproportionately impacts minority groups. In Australia, Indigenous Australians account for 92% of cases despite only representing 3.8% of the population. Studies to date, such as the INVICTUS trial, support the use of Vitamin K antagonists (VKAs) over direct oral anticoagulants (DOACs) in vAF. However, this assumes consistent adherence and regular clinic follow up. Reduced access to monitoring and dispensing clinics in Central Australia remains a challenge in the provision of VKAs and the use of DOACs may address this. Hypothesis: DOACs may be comparably effective with VKAs in preventing major adverse cardiac and cerebrovascular events (MACCE) in a real-world vAF population. Aim: To conduct a real-world retrospective observational study examining rates of MACCE for patients on VKAs or DOACs for vAF in Central Australia over a five-year period. Methods: The Northern Territory RHD Register was accessed to identify patients with RHD and vAF in January 2019. Demographic and five-year outcome data (until January 2024) were collected. The primary outcome was MACCE, a composite of ischaemic stroke, systemic embolism, non-fatal myocardial infarction, cardiovascular death and all-cause mortality. The primary safety endpoint was major bleeding. Statistical analyses were conducted as both intention-to-treat (ITT) based on initial anticoagulation and as-treated (AT) based on anticoagulation prior to MACCE or trial endpoint, each excluding patients without anticoagulation. Results: 61 patients were included. The mean age was 61.9 ± 13.9 years and 68.9% were female. At baseline, 65.6% received VKA, 14.8% DOAC and 19.7% were not anticoagulated. 30.6% of patients crossed over from the ITT analysis, with a non-significant trend favouring switch to DOAC (11 vs 0, p=0.09). In the ITT analysis (n=49), there was no significant difference in MACCE (25.0% vs 22.2%, p=0.86) or major bleeding (20.0% vs 11.1%, p=0.53) between VKA and DOAC groups. In the AT analysis (n=51), there was no significant difference in MACCE (27.3% vs 16.7%, p=0.39) or major bleeding (18.2% vs 22.2%, p=0.73) between VKA and DOAC groups. Conclusion: Over a five-year period, there was a trend towards use of DOACs over VKAs in vAF. This study demonstrates that DOACs may be as effective as VKAs for reducing MACCE in a real-world vAF population however further investigation is required.

Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

Systematic vitamin K antagonist reversal with prothrombin complex concentrate in patients with mild traumatic brain injury: randomized controlled trial.

Traumatic brain injury (TBI) in patients on vitamin K antagonists (VKAs) is linked to a high rate of intracranial hemorrhage (ICH). Rapid reversal can reduce ICH progression and mortality, but its effectiveness depends on the time between bleeding onset and coagulation normalization. The PREVACT study aimed to assess the efficacy and safety of prompt systematic reversal of anticoagulation in patients presenting to emergency departments (EDs) for recent mild-TBI while receiving a VKA. A randomized, open-label, blinded-endpoint clinical trial was conducted in 21 French EDs. Patients receiving a VKA, having experienced a TBI within the last 6 h, and presenting a Glasgow Coma Score ≥13 were included. Patients were randomized to systematic immediate VKA reversal with 25 IU/kg of four-factor prothrombin complex concentrate (4f-PCC) before any investigation (intervention group) or standard-of-care signifying reversal only if the initial cranial computed tomography (CT) scan indicated ICH (control group). The primary outcome was the rate of ICH detected on a cranial CT scan 24 h post-inclusion. The study was prematurely stopped for logistic reasons after the randomization of 202 patients (101 and 101 in the intervention and control groups, respectively, mean age 90; 51.8% female). On the 24-h cranial CT scan, 6 of 98 patients (6.1%) in the intervention group manifested ICH vs. 12 of 99 patients (12.1%) in the control group [odds ratio: 0.47 (95% confidence interval: 0.14-1.44); P = 0.215]. In patients with recent mild-TBI receiving a VKA, systematic prompt reversal with 4f-PCC did not statistically significantly reduce ICH rate at 24 h. However, the study was prematurely stopped and does not exclude a clinically relevant benefit of the strategy tested. Clinicaltrials.gov (NCT01961804).

Efficacy and Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients with Cirrhosis and Splanchnic Vein Thrombosis.

The incidence of splanchnic vein thrombosis (SVT) is reported to be <25 times lower than that of deep vein thrombosis and pulmonary emboli, which occur in 70 to 270/100,000 cases in the general population. Current guidelines recommend initial treatment with therapeutic low-molecular-weight heparin followed by a transition to a vitamin K antagonist (VKA) or a direct oral anticoagulant (DOAC) in patients with cirrhosis who develop SVT without severe liver dysfunction. This, however, is based on observational data. This study aimed to evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhosis who present with SVT and receive either a DOAC or a VKA. This multicenter retrospective cohort study was conducted from December 2021 to November 2022. Patients between the ages of 18 and 75 years with cirrhosis and acute SVT who received either a VKA or a DOAC between July 2019 and July 2021 were eligible for inclusion. The primary outcome was the efficacy of treatment, defined as a new thrombotic event. The secondary outcome was the safety of treatment, defined as the development of major bleeding. Readmission data were followed up at 6 and 10 months. Bivariate analysis was conducted to assess the relationship between the medication groups and each outcome and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at 5% for all of the comparisons. A total of 80 patients from 50 hospitals were included in this study. Sixty-one patients (59.02% male) received DOACs and 19 (57.89% male) received a VKA. Of the patients who received DOACs, 41 (67.21%) received apixaban, one (1.64%) received dabigatran, and 19 (31.15%) received rivaroxaban. The results from the bivariate analysis revealed no significant differences between DOACs and warfarin for both the efficacy (OR 1.46, 95% CI 0.44-4.84, P = 0.53) and safety outcomes (OR 1.03, 95% CI 0.04-26.43, P = 1) at 10 months. The use of DOACs in patients with cirrhosis who present with SVT may be efficacious and safe compared with warfarin. The findings from our study may inform power analyses for well-conducted randomized trials to confirm these findings.

Clinical Features, Management, and Recurrence of Acute Ischemic Stroke Occurring in Patients on Oral Anticoagulant Treatment for Nonvalvular Atrial Fibrillation: A Real-World Retrospective Study.

The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF). We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded. A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P =0.358; 92.3% vs. 74.3%, P =0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P =0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences. In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted.

Apixaban plasma levels in patients with HeartMate 3 support

BackgroundApixaban is increasingly used instead of vitamin K antagonists (VKAs) for long-term anticoagulation during HeartMate 3 (HM3) support. However, data on its pharmacokinetics in this context is lacking. We present real-world data on apixaban levels and outcomes in adult and pediatric HM3 patients, and evaluate our dosing strategy based on plasma sampling. MethodsSince June-2023, all new HM3 recipients were initiated on apixaban. Additionally, hospitalized adult HM3 patients were transitioned from VKA to apixaban. Trough apixaban levels were measured in all patients, and dose adjustment was considered to exceed 50ng/mL. ResultsThis retrospective study includes 34 HM3 patients, 4 pediatric (all primary use) and 30 adult patients (16 primary use). In primary use, apixaban was started at median of 14 (IQR:11-16, pediatric) and 11 (IQR:6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3191 patient-days. Six minor bleeding events occurred (0.69 events per patient-year), mostly (67%) during dual therapy with aspirin. Fourteen patients had dose adjustment; median trough and peak levels on final dosage were 73 (IQR:50-92) and 179 (IQR:133-242) ng/mL in the pediatric group and 109 (IQR:83-144) and 176 (IQR:134-228) ng/mL in the adult cohort, respectively. Inter- and intraindividual variation in apixaban peak levels was considerable, while trough levels showed less variability. ConclusionsWith a dosing strategy to target trough apixaban levels of >50ng/ml, there were no thrombotic events during a follow-up of 3191 patient-days (of which 820 patient-days in children). We observed no major, and only few non-major bleeds, mainly in patients concomitantly taking aspirin.

From the INVICTUS Trial to Current Considerations: It's Not Time to Retire Vitamin K Inhibitors Yet!

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.

The effect of Vitamin K antagonists as anticoagulants on bleeding in patients post-dental procedures

Background: Individuals undergoing continuous treatment and taking vitamin K antagonist (VKA) and other anticoagulant medications are at a higher risk of experiencing bleeding complications during and after dental surgery procedures. Objective: To determine the effect of vitamin K antagonists in post-dental procedure patients by exploring existing literature on managing patients on vitamin K antagonist therapy as anticoagulants. Methods: This research utilized a literature review based on a database search of studies published between 2019-2024. The literature search used strategies with the terms “Tooth extraction bleeding,” “Odontectomy bleeding,” “Vitamin K Antagonist,” and “Anticoagulant,” utilizing databases such as PubMed, Science Direct, and SCOPUS related to the research topic and meeting eligibility criteria. The studies were then reviewed, summarized, and conclusions were drawn using tables to reveal all data regarding study characteristics and results. Results: Patients using anticoagulants are categorized as high risk for bleeding when undergoing invasive dentistry procedures. VKA is the most commonly used anticoagulant to prevent blood clotting. The consumption of VKA does not significantly affect bleeding post-procedure. Dental procedures can be performed on patients taking anticoagulants without discontinuing the therapy. Conclusion: Based on several studies from various literature sources, it can be concluded that dental procedures in patients taking vitamin K antagonist anticoagulants can still be performed without the risk of bleeding complications with proper local hemostatic measures and perioperative management.

Consequences of the Poor Anticoagulation Control of Patients with Non-Valvular Atrial Fibrillation Treated with Vitamin K Antagonists.

Background: The prevention of thromboembolisms through anticoagulation and heart rate control is crucial in managing non-valvular atrial fibrillation (NVAF). This study aimed to analyze the consequences of poor anticoagulation control with vitamin K antagonists (VKAs) in Spanish patients with NVAF, focusing on thrombotic events, bleeding, mortality, healthcare resources (HRU), and costs. Methods: This observational, retrospective study used electronic medical records (BIG-PAC® database) of NVAF patients who started VKA treatment between 1 January 2016 and 31 December 2018. Patients were followed up for two years and classified by poor or adequate anticoagulation control. Demographic and clinical characteristics, treatments, incidence of cardiovascular events, mortality rates, HRU, and costs were analyzed. Results: Patients with poor control (n = 2136) had a 75% greater probability of suffering a cardiovascular event compared to patients with adequate control (n = 2351) (HR, 1.75 [95%CI: 1.43-2.14; p < 0.001]). Cardiovascular events, major bleeding, minor bleeding, systemic thromboembolism, and ischemic strokes were reduced by 32.1%, 46.2%, 29.6%, 22.2%, and 16.1%, respectively. It was estimated that adequate anticoagulant control saved EUR 455/patient with NAVF due to reduced hospitalization for cardiovascular events. Conclusions: For VKA-treated NVAF patients, poor anticoagulation control was associated with a higher number of cardiovascular events, greater consumption of HRU, and higher management costs than for patients with adequate control.

Long-term Impacts of Long COVID: Increased Incidence of Cardiomyopathies, Joint Diseases, and Psychoanxiety Disorders.

The COVID-19 pandemic has intensified inquiries into the interplay between diabetes and disease severity, and the long-term impact of long-COVID. This study specifically explored the implications of different antithrombotic treatments on COVID-19 patients. It aimed to assess the long-term efficacy and safety of Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) in mitigating thromboembolic complications in COVID-19 patients. We conducted a study on 157 patients diagnosed with COVID-19 from August 2021 to August 2023. The study evaluated shifts in anticoagulant therapy recommendations, tracking the transition from VKA to DOACs, and analyzed associated health outcomes. A significant shift from VKA to DOACs prescriptions was observed, especially in high-risk patients. Despite the change in antithrombotic treatments, incidences of varices and varices with hemorrhoids increased by 2.6% and 3.2%, respectively. Long-COVID was also linked to higher occurrences of diabetes and gastrointestinal diseases. Joint diseases rose by 14%, indicating persistent inflammation. Cardiomyopathies increased by 3.9%, predominantly in high-risk groups, and psychoanxiety disorders surged by 39.5%, highlighting the need for further research. DOAC usage was more common in older age groups, with a 10.2% increase in recommendations among high-risk patients (p<0.05). The study underscores the evolving landscape of antithrombotic therapy in managing COVID-19 complications. Despite the increased use of DOACs, the rise in various health conditions suggests the necessity for personalized treatment strategies tailored to patient risk profiles.

Impact of resumption of Oral AntiCoagulation therapy (OAC) after GastroIntestinal Bleeding (GIB) on clinical outcomes in patients with Non-Valvular Atrial Fibrillation (NVAF)

Abstract Purpose Optimal resumption of oral anticoagulation therapy (OAC) after gastrointestinal bleeding (GIB)has not been well established. This study aimed to compare clinical outcomes between patients who resumed or discontinued OAC after index GIB. Methods We retrospectively enrolled consecutive patients with non-valvular atrial fibrillation (NVAF) and prior GIB from January 2018 to July 2022 in 16 public hospitals in Hong Kong. Resumption of OAC was substantiated by new prescription after index GIB on electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Endpoints included recurrent GIB, ischemic stroke and all-cause death. Risks of target events were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk for recurrent GIB and stroke, and COX proportional regression for all-cause mortality, adjusting for components of CHA2DS2VASC, HASBLED scores, causes of index GIB (i.e., GI ulcer, diverticular disease, angiodysplasia or undermined) and endoscopy intervention. Among patients who resumed OAC, outcomes were compared between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference. Results Of 2,350 patients identified (mean age 80.5±10.4, female 54.5%), 44.0% (n=1,034) were OAC naïve, 4.4% (n=103) discontinued VKA, 11.7% (n=275) discontinued DOAC, 11.2% (n=263) resumed VKA, and 28.7% (n=675) resumed DOAC. During a median follow-up duration of 1.2(IQR:0.2-2.5) years, discontinuation of DOAC (aSHR=0.5(0.29-0.9) was associated with lower risk of recurrent GIB, whereas resumption of VKA (aSHR=1.8(1.0-3.1)) was associated with the highest risk of recurrent GIB (Figure 1a). Among DOACs, apixaban (aSHR=0.5(0.3-0.9)) was associated with the lowest risk of recurrent GIB (Figure 1b). Risk of ischemic stroke across groups were similar. Patients who discontinued DOAC (aHR=1.4(1.2-1.6)) were at higher risk of all-cause mortality, whereas resumption of VKA (aHR=0.4(0.3-0.6)) and DOAC (aHR=0.4(0.4-0.5)) were both associated with decreased mortality (Figure 1c). Conclusion In this real-world dataset, resumption of VKA in NVAF patients after GIB was associated with high risk of recurrent GIB and lowest risk with apixaban. OAC resumption either VKA or DOAC was associated with reduced mortality.

Resumption of anticoagulation therapy among Non-Valvular Atrial Fibrillation (NVAF) patients with prior intracranial haemorrhage

Abstract Purpose Resumption of anticoagulation therapy (OAC) in patients with non-valvular atrial fibrillation (NVAF) suffering from intracranial haemorrhage (ICH) is challenging in clinical practice. The aim of this study was to evaluate impact of resumption of OAC on clinical outcomes in NVAF patients with history of ICH. Methods Consecutive patients with NVAF with or without OAC who survived from an index ICH between January 2018 and July 2022 in 16 public hospitals in Hong Kong were identified and analyzed retrospectively. Resumption of OAC was substantiated by new prescription obtained from electronic medical records. Patients were divided into 5 groups: (i) OAC naïve (as reference group); (ii) resume direct oral anticoagulant (DOAC); (iii) resume Vitamin K antagonist (VKA); (iv) discontinue DOAC; (v) discontinue VKA. Risks of ischemic stroke, recurrent ICH and all-cause mortality were estimated for all groups and compared with individuals without OAC, using adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression models, accounting for death as competing risk, adjusting for components of CHA2DS2VASC and HASBLED scores. Sub-analysis was conducted to compare outcomes between different DOAC agents (i.e, apixaban, dabigatran, edoxaban, rivaroxaban), using VKA as reference among patients who resumed DOAC or VKA. Results Of 982 patients who met inclusion criteria (mean age 77.7±10.9, female 40.9%), 39.1% (n=384) were OAC naive, 32.2% (n=316) resumed DOAC, 12.6% (n=124) resumed VKA, 9.0% (n=88) discontinued DOAC and 7.1% (n=70) discontinued VKA. During a median follow-up period of 2.0 (IQR: 0.7-3.5) years, no statistically significant difference in risk of ischemic stroke was observed among 5 groups. Discontinuation of DOAC was associated with markedly higher risk of ischemic stroke (aSHR=8.32 (1.8-39.3)) only among AF patients with CHA2DS2VASC score ≥ 4, Risk of recurrent ICH was higher in patients who resumed VKA (aSHR=1.6(1.0-2.5)). Sub-analysis demonstrated resumption of apixaban was associated with lowest risk of recurrent ICH (aSHR=0.6(0.4-0.9)). Compared to OAC naïve patients, those who resumed DOAC (aSHR=0.5(0.4-0.7)) had lowest risk of all-cause mortality, whereas discontinuation DOAC (aSHR=1.9(0.4-2.5) and VKA (aSHR=1.6(0.2-2.2)) were both associated with increased mortality. Conclusion Our real-world data revealed among NVAF patients with prior ICH long term discontinuation of OAC was associated with increased risk of ischemic stroke. Recurrent ICH was highest among patients who resumed VKA and lowest with apixaban.