Vitamin K Antagonists Therapy Research Articles

Left Atrial Appendage Closure in Patients With a Mechanical Mitral Valve Prosthesis: A Multicentre Italian Pilot Study

BackgroundIn patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutic international normalized ratio (INR) range, the incidence of cardiac thromboembolism is not negligible, and the subgroup of patients who have a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients with a mechanical PMV who experienced a failure of VKA therapy. MethodsIn this retrospective, multicentre study, patients underwent LAAC because of thrombotic events including transient ischemic attack and/or stroke, systemic embolism, and evidence of left atrial appendage thrombosis and/or sludge, despite VKA therapy, were enrolled. Patients with a mechanical PMV were included and compared with those affected by nonvalvular AF. The primary endpoint was the composite of all-cause death, major cardiovascular events, and major bleedings at follow-up. The feasibility and safety of LAAC also were assessed. ResultsA total of 55 patients (42% female; mean age, 70 ± 9 years), including 12 with a mechanical PMV, were enrolled. The most-frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases, and in 100% of patients with a PMV. In 35 patients, a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with a PMV, and 20 patients without a PMV, reported adverse events (hazard ratio 0.73 [95% confidence interval 0.25-2.16, P = 0.564]). ConclusionsLAAC seems to be a valuable alternative in patients with AF who have a mechanical PMV, with failure of VKA therapy. This off-label, real-world clinical practice indication deserves validation in further studies.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

BackgroundWe investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.MethodsThis is an individual patient...

Living on Oral Anticoagulants: Duke Anticoagulation Satisfaction Scale Results.

Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. The lack of the need for laboratory monitoring and a better safety than vitamin K antagonists (VKAs) has probably changed the quality of life of patients on these oral anticoagulants. This was a real-life prospective observational cohort study. The aim was to evaluate if a long-term treatment with DOACs could offer a better quality of life than VKAs. Moreover, age, gender, education level, time in therapeutic range for VKAs, taking medication once or twice a day for DOACs, the total daily number of medications and thrombotic and bleeding complications were considered as variables probably associated with the quality of life of these patients. Between January and December 2021, the Duke Anticoagulation Satisfaction Scale (DASS) 25-items was administered as an interview to patients on either VKAs or DOACs therapy. During the follow-up period, all of the patients were closely monitored to evaluate possible bleeding and thrombotic events. The analysis included 300 outpatients treated with VKAs and 254 treated with DOACs. In general, the quality of life was better in patients taking DOACs (DASS total score: DOACs = 44.7, 42.9-46.5 vs. VKAs = 51, 49.2-52.8, p < 0.0001) as the daily-life limitations, hassles and burdens and the psychological impact were less important than in patients on VKAs therapy. VKAs negatively influence the daily-life of the patients in terms of both less satisfaction and time-consuming tasks. DOACs confer a better quality of life even if some concerns emerge from not knowing how their therapy is working.

Impact of Quality and Type of Anticoagulant Treatment, and Inflammatory Biomarkers on Quality of Life and Psychological Morbidity in Patients with Atrial Fibrillation: An Exploratory Study

Background: Owing to increasing worldwide life expectancy, the step rise in the prevalence of atrial fibrillation (AF) represents an urgent public health issue. Indeed, AF can severely affect a patient's quality of life (QoL) since it is associated with serious outcomes, such as stroke, cardiac failure, and cognitive impairment/dementia, resulting in increased morbidity and mortality and a burden for health-care systems. Anticoagulation therapy prevents stroke in individuals with AF, whether with vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs). So far, effective AF management is missing since its etiology is unraveled. Within the research project [Cognitive Decline Risk Profiles and Quality of Life in Atrial Fibrillation: A Longitudinal Study- 2022.072(057-DEFI/058-CE)] a pilot study was conducted to assess a dynamic cohort of AF outpatients who attended the anticoagulation clinic at Santo António University Hospital Center, a Portuguese university public hospital. In this study, QoL, distress and cognitive impairment in patients with AF was assessed considering quality and type of anticoagulant treatment. Methods: With a cross-sectional design, quality of anticoagulation therapy was measured calculating Time in Therapeutic Range (TTR) using Rosendaal method for patients under VKA (TTR&amp;gt;70% as good control); for those patients under DOAC, the presence of plasma therapeutic levels of this drug, taking into account the time of blood sampling, meant an anticoagulant treatment of quality. QoL and distress were assessed by the Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. Cognitive impairment was assessed by the Montreal Cognitive Assessment (MoCA) scale. Data on sociodemographic, clinic [medical history including quality and type of anticoagulation therapy, stroke(CHA2DS2-VASc) and bleeding(HAS-BLED) risk scores, duration of illness) and inflammatory biomarkers were also collected. Results: A total of 62 AF patients were included (mean age 74.4±10.2 years, 59.7% women) with a mean CHA2DS2-VASc of 4.3±1.6 and HAS-BLED of 2.6±1.2. Fifty patients (80.6%) were on VKA and twelve (19.4%) on DOACs (all in apixaban). Those individuals under VKA showed a mean TTR score of 77.1 ± 14.7% (67.4% with a good control) and 11 patients in apixaban presented DOAC therapeutic plasma level. Participants had an illness duration average of 16.02 years±10.62. The mean scores of AFEQT was 2.65 ± .93 showing a good QoL and for MoCA was 21.66 ± 3.90 indicating mild cognitive impairment. Regarding anxiety, depression, and stress (DASS-21) the mean scores were 4.27 ± 4.08, 6.52 ± 4.92 and 7.37 ± 5.37, respectively showing non-clinical psychological morbidity. Patients with higher plasmatic levels of C Reactive Protein (CRP) reported more depression (r= .482; p= .005) and those with a longer illness duration presented a higher level of cognitive impairment, (r= -.398; p= .001). No other associations were found between inflammatory biomarkers and psychological variables. There were significant differences according to sex, age, and illness duration, with women reporting lower QoL (p = .002), higher depression (p = .004), higher stress (p = .005) and older patients (p = .017) as well as patients under VKA and longer disease duration reporting better TTR. (p = .007). No differences were found on patients' QoL (p = .342), anxiety (p = .370), depression (p = .167) and stress (p = .117), cognitive impairment, (p = .084) between good and non-good quality of anticoagulant treatment and between VKA versus DOAC therapy (p = .444). Conclusion: The majority of the patients showed good quality of anticoagulation and QoL, but they revealed mild cognitive impairment. Patients' QoL, distress and cognitive impairment were independent of quality and type of anticoagulation treatment. Older AF patients, particularly those with longer diagnosis, should be assessed for cognitive function on a regular basis, preventing dementia and economic burden. The association of depression with higher levels of CRP in AF patients underlines the nature of these two inflammatory conditions that coexisting associate to worse outcomes. Future studies should assess cognitive function over time to unravel the pathophysiology of cognitive decline and the effect of AF treatments on cognition to optimize and personalize AF therapy.

Quality of Oral Anticoagulation with Vitamin K Antagonists and Direct Oral Anticoagulants in ‘real-World’ Patients: Lessons from a Five Years Audit Study

Background: Even with the introduction of direct oral anticoagulants (DOACs), anticoagulation clinics (ACs) stand with a key role in monitoring. Indeed, routine evaluation by health care professionals is recommended as it is with vitamin K antagonists (VKA) with adjustments in practices of anticoagulation management services. Quality of oral anticoagulation (QOA) is associated to better clinical outcomes in those patients with indications for such therapy. It is well established that patients receiving VKA therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. It has been reported that ACs should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. So far, QOA for DOACs is not fully established. Aim: Since few clinical data are available considering the new era of ACs, this study aims to describe actual trends and QOA of an AC at a large academic medical hospital. Methodology: We retrospectively analyzed 23275 appointments of 5 consecutive years (May 2018 to May 2023), corresponding to 930 patients that are regularly followed up at an outpatient AC of a central hospital under anticoagulation for at least 8 weeks. TTR (≥70%) determined by Rosendaal method was used for patients under AVK and for those individuals in DOACs, QOA was considered the presence of therapeutic plasma levels of the drugs after the European Heart Rhythm Association 2021 in, at least, one determination. Patients were divided according to target INR in 3 groups: Group 1 with target INR 2-3, including 809 patients mean age 65±18 years (mean±SD), majority (36.6%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 92 patients with mean age 70±11 years, majority (85.9%) with mechanical heart valves; Group 3 with target INR 3-4, including 29 patients with mean age 63±15 years, majority (55.5%) with antiphospholipid syndrome. Seventy patients were under DOACs (apixaban in 74.3%), with mean age of 71±17 years, majority (62.9%) with non-valvular AF, were included in Group 1 and all individuals were under direct inhibitors of factor Xa. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests were performed. Results: The 930 patient population, 52.2% female, mean age of 65±18 years and 87% in Group 1, showed a mortality of 17%. The mean recall interval between appointments was superior to 90 days in 94% of the population. The individuals who died in comparison with the survivors showed higher frequency of AF (54.1%) [ χ 2= 47.099; p&amp;lt;.001; φ=.225], were from Group 1 (93%) [ χ 2= 6.641; p=.036; φ=.085], male (59.2%) [ χ 2= 10.103; p=.001; φ=-.104] and older [76±12 vs .63±18 years (p&amp;lt;.001), respectively]. No differences were noticed in mortality between AVK and DOACs [ χ 2= 1.828; p=.401; φ=-.044], even DOAC patients being older than AVK patients (71±17 vs 65±17; p=.005), respectively. QOA associated with mortality being the individuals who died with higher frequency of no QOA (21.9% vs 13.9%) [ χ 2= 8.126; p=.004; φ=-.101] respectively. The individuals on AVK from Group 1 corresponding to 86% of total population showed a mean TTR of 76%, patients from Group 2 had a TTR of 72% and patients in Group 3 had TTR of 55%. From the individuals under DOACs, only 30% had at least one determination of plasma levels of the drug and all but one showed therapeutic levels. Comparatively with our previous studies related to the periods of 2006-2012 and 2012-2018, we noticed a significant decrease in patient population / appointments size (2087/ 61988) (1587/ 37931),(p &amp;lt;.001) with an increase of TTR in Group 1 (1927/1430 patients) (83% /72%) and Group 2 (120/125 patients) (74% / 69%) but a TTR decrease in Group 3 (40 / 32 patients) (54% / 60%) (p &amp;lt;.001). respectively. Mortality in the 2012- 2018 period was 18%. Conclusions and Discussion: The trends of decreasing the number of anticoagulated patients at our AC with an overall good quality of monitoring but with a low percentage of individuals under DOACs suggests that the majority of anticoagulated population is on these drugs without routine follow up in opposition to the recent recommendations. Our study underlines the importance of the quality of anticoagulation monitoring on mortality that was no different from the previous years before SARS-CoV- 2 pandemic nor between AVK and DOACs.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure

Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. ClinicalTrials.gov Identifier: NCT04069156.

Direct oral anticoagulants versus vitamin K antagonists for left ventricular thrombus: a systematic review and meta-analysis

Abstract Introduction Left ventricular thrombi (LVTs) increase the risk of stroke and systemic embolism and are commonly seen after acute myocardial infarction. While vitamin K antagonists (VKAs) are the recommended first-line treatment for LVT, direct oral anticoagulants (DOACs) are being used as an alternative. However, the comparative efficacy and safety of DOACs and VKAs in LVT treatment are unclear. Purpose We conducted a systematic review with meta-analysis to evaluate the impact of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for studies that compared DOACs versus VKAs and reported efficacy and safety endpoints. We performed meta-analyses with fixed or random effect models based on the level of heterogeneity determined by the Cochrane Q-test and I2 statistics. Results Three randomised controlled trials (RCTs) and 29 cohort studies were included, with 4,400 patients assigned to either DOACs (1,307 patients) or VKAs (3,093 patients). Our findings indicate that DOACs therapy did not significantly reduce stroke/systemic embolic events (OR 0.90; 95% CI 0.65-1.26; p=0.54; I2=33%), stroke (OR 0.90; 95% CI 0.59-1.36; p=0.60; I2=7%), systemic embolic events (OR 0.65; 95% CI 0.39-1.06; p=0.08; I2=0%), thrombus resolution (OR 1.11; 95% CI 0.92-1.33; p=0.27; I2=0%), minor bleeding (OR 0.68; 95% CI 0.39-1.18; p=0.17; I2=0%), major bleeding (OR 0.84; 95% CI 0.47-1.49; p=0.54; I2=16%), or all-cause mortality (OR 1.01; 95% CI 0.75-1.36; p=0.97; I2=0%) compared to VKAs. However, DOACs therapy was associated with a statistically significant reduction in any bleeding (OR 0.72; 95% CI 0.55-0.96; p=0.02; I2=0%) and clinically relevant bleeding (OR 0.62; 95% CI 0.41-0.92; p=0.02; I2=0%) compared to VKAs therapy. Our subgroup analysis of patients treated with apixaban revealed no significant differences between DOACs and VKAs therapies for stroke, clinically relevant bleeding, and all-cause mortality. Conversely, rivaroxaban therapy was associated with a statistically significant reduction in systemic embolic events and clinically relevant bleeding compared to VKAs therapy. Conclusion DOACs therapy was not associated with reduced efficacy and safety endpoints compared to VKAs therapy, except for fewer haemorrhagic events. Rivaroxaban therapy had a significant reduction in systemic embolic and hemorrhagic events. These findings support the superiority of DOACs over VKAs therapy for LVT.PRISMA Flow-ChartForest plot of odds ratios (OR)

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF &amp;lt; 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation: a systematic review and meta-analysis

Abstract Background The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) have not been well established yet. Purpose This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. Methods PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. Results Five studies involving 8103 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a significant lower risk of all-cause death [RR (95%CI): 0.44 (0.35-0.55)]. Meanwhile, DOAC therapy group was similar to VKA therapy in reducing ischemic stroke [RR (95%CI): 0.65 (0.33-1.28)] and thromboembolic events [RR (95%CI): 0.95 (0.74-1.22)]. The incidence of major bleeding [RR (95%CI): 0.69 (0.44-1.07)] were comparable between the two groups. Conclusion In patients with HCM and AF, DOAC therapy were superior or non-inferior to VKA therapy in reducing the risk of all-cause death and thromboembolic events, without increasing bleeding risk. Further RCTs are needed to provide more evidence for DOAC therapy in this population.Efficacy and safety endpoints in DOAC th

Abstract 17888: Apixaban versus Vitamin K Antagonists for Left Ventricular Thrombus: A Systematic Review and Meta-Analysis

Introduction: Left ventricular thrombus (LVT), a major complication following acute myocardial infarction, significantly contributes to the increased risk of stroke and systemic embolism. Although vitamin K antagonists (VKAs) are the first-line treatment for LVT, direct oral anticoagulants (DOACs) have emerged as a potential alternative. However, the comparative effectiveness and safety of DOACs and VKAs for LVT treatment remain uncertain. Research question: Is apixaban therapy more effective and safer than VKA therapy for LVT? Aim: To assess the efficacy and safety of apixaban compared with VKAs therapy in patients with LVT. Methods: We systematically searched PubMed, Embase, and Cochrane databases for studies comparing the efficacy and safety of apixaban versus VKAs. We applied the random-effects model to calculate odds ratios (OR) and the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. All calculations and graphics were performed using R (version 4.2.3). Results: Three randomized clinical trials (RCTs) were included, with 109 patients assigned to either apixaban (56 patients) or VKAs (53 patients). Compared to VKAs, apixaban showed no significant impact on thrombus resolution (OR 0.69; 95% CI 0.11-4.50; p=0.70; I 2 =0%), stroke reduction (OR 0.91; 95% CI 0.09-9.38; p=0.93; I 2 =1%), clinically relevant bleeding (OR 0.21; 95% CI 0.02-1.99; p=0.17; I 2 =0%), or all-cause mortality (OR 0.65; 95% CI 0.11-3.78; p=0.63; I 2 =8%). Conclusions: Apixaban therapy showed similar efficacy and safety to VKAs for LVT. These findings support the use of apixaban as an alternative to VKAs in LVT treatment.

Abstract 19017: Peri-Operative Bridging Requirement for Patients Chronically Taking Direct Oral Anticoagulants (DOACS) or Vitamin-K Antagonists (VKA) Before Undergoing the Elective Procedure: A Systematic Review and Meta-Analysis

Introduction: Many patients undergo elective interventions/surgical procedures while being on direct oral anticoagulants (DOACs) or vitamin-K antagonists (VKA) chronically. There is limited data on peri-procedural management of DOACs in patients undergoing elective procedures. It is also unclear if there is any role of peri-procedural bridging in patients on chronic VKA therapy. We conducted this study to evaluate the efficacy and safety of DOACs (continued vs. interrupted)and VKAs (with vs. without bridging) among patients undergoing elective procedures. Methods: This systematic literature review was conducted according to PRISMA guidelines until 10 th June 2023. The following inclusion criteria were used: adults, chronic use of VKAs or DOACs, elective procedures, and clinical trials. Primary endpoints were major bleeding, stroke, MI, and VTE. A generic variance random effects model was used to estimate odds ratios using CMA III. Heterogeneity and quality of studies were quantified via I 2 statistic and GRADE score, respectively. Results: 14 clinical trials were included (n=15683). There was no difference in the risk of major bleeding (OR: 1.06, 95% CI: 0.65 -1.7, I2: 46%) or risk of stroke(OR: 1.10, 95% CI: 0.66 - 1.84, I2: 0%) whether DOACs were held or continued respectively. Among patients on VKA, there was no difference in risk of major bleeding in bridging vs. no bridging groups (OR: 2.02, 95% CI: 0.87 - 4.71, I2:75%). There was no difference in the rates of stroke (OR: 0.44, 95% CI: 0.12 -1.58, I2: 0%), MI (OR: 1.64, 95% CI: 0.76 - 3.53, I2: 0%), and VTE (OR: 1.26,95% CI: 0.31 - 5.01, I2: 0%). The quality of included studies was low to moderate. Conclusion: Patients undergoing elective procedures and chronically taking DOACs have a similar risk of major bleeding and stroke when DOACs are continued or interrupted peri procedurally. Similarly, among patients on VKA who were bridged or not bridged, there was no difference in risk of bleeding, stroke, MI or VTE.

Effect of Some Risk Factors on Over-Anticoagulation Disorders and Bleeding in Patients Receiving Anticoagulant Therapy with Overdosage of Vitamin K Antagonist.

Study on effect of risk factors on over-anticoagulation in patients taking anticoagulant drugs with VKAs (vitamin K antagonists). Cross-sectional descriptive, prospective research. Study on 79 patients taking anticoagulant drugs with VKAs who had an INR (International Normalized Ratio) index of more than indicated anticoagulation dose with VKAs therapy. A total of 79 patients, mean age 65.65 ± 12.17 years [33:85], the elderly group is common (73.4%). Patients had hemorrhage disorders account for 22.8%. The INR index had an average value was 5.88 ± 3.0 [3.02-23.95]; The INR> 5 level group is a higher risk of bleeding than the INR ≤5 level group, it's the statistical significance (p < 0.001). The risk factors such as drugs to treat dyslipidemia, hyperthyroid, amiodarone, beta blocker, prednisone, NSAIDs (Non-steroidal anti-inflammatory), BMI (Body Mass Index), smoke and alcohol that the risk factors of increasing of bleeding when receiving anticoagulants but it's not statistically significant yet (OR >1, p > 0.05); These patients using coenzyme Q10 and green vegetable nutrition such as cruciferous vegetables (Brassicaceae, Asteraceae) are quite common (31.6% and 35.4%), its effect on coagulation with vitamin K and cause of the increased in risk of bleeding was statistical significantly with OR = 5.28 (CI: 1.72-16.17, p < 0.01), and OR = 2.99 (CI: 1.01-8.80, p < 0.05) respectively. Most patients in over-anticoagulation were the elderly group. Patients had hemorrhage disorders account for 22.8%. The INR> 5 level group was a higher risk of bleeding than the INR ≤5 level group with statistical significance. Patients using Coenzyme Q10 and green vegetable nutrition such as cruciferous vegetables (Brassicaceae, Asteraceae) are quite common, its effect on coagulation and cause of the increased risk of bleeding complication with statistical significance.

Effect of previous INR control during VKA therapy on subsequent DOAC adherence and persistence, in patients switched from VKA to DOAC.

Introduction Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR<70%). Poor INR control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC non-adherence and non-persistence, in patients who switched from VKA to DOAC. Methods 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen and Statistics Netherlands. DOAC prescriptions were used to determine non-adherence and non-persistence. INR control (i.e. TTR, time under therapeutic range (TUR) and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC non-persistence / non-adherence. Results On VKA, 67.7% of the patients had a TTR below 70%. DOAC non-persistence was 39.8% (95% CI 33.4-45.5%) during a median follow-up of 34.4 months [IQR 19.1-49.2]. Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC non-persistence (HR 1.14, 95% CI 0.69-1.87) and DOAC non-adherence (OR 1.38, 95% CI 0.67-2.84), nor were TUR and INR variability. Conclusion Previous INR control during VKA therapy is not associated with subsequent DOAC non-adherence and non-persistence. This study suggests that INR control on VKA cannot, and therefore should not be used for predicting DOAC adherence or persistence.

A comparison of the effects of NOAC and VKA therapy on the incidence of dementia in patients with atrial fibrillation: A systematic review and meta-analysis.

Atrial fibrillation (AF) patients are more susceptible to dementia, but the results about the effect of oral anticoagulants (OACs) on the risk of dementia are not consistent. We hypothesize that OAC is associated with a reduced risk of dementia with AF and that nonvitamin K antagonist oral anticoagulants (NOAC) are superior to vitamin K antagonists (VKA). Four databases were systematically searched until July 1, 2022. Two reviewers independently selected literature, evaluated quality, and extracted data. Data were examined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Fourteen research studies involving 910 patients were enrolled. The findings indicated that OACs were associated with a decreased risk of dementia (pooled HR: 0.68, 95% CI: 0.55-0.82, I2  = 87.7%), and NOACs had a stronger effect than VKAs (pooled HR: 0.87, 95% CI: 0.79-0.95, I2  = 72%), especially in participants with a CHA2DS2VASc score ≥ 2 (pooled HR: 0.85, 95% CI: 0.72-0.99). Subgroup analysis demonstrated no statistical significance among patients aged <65 years old (pooled HR: 0.83, 95% CI: 0.64-1.07), patients in "based on treatment" studies (pooled HR: 0.89, 95% CI: 0.75-1.06), or people with no stroke background (pooled HR: 0.90, 95% CI: 0.71-1.15). This analysis revealed that OACs were related to the reduction of dementia incidence in AF individuals, and NOACs were better than VKAs, remarkably in people with a CHA2DS2VASc score ≥ 2. The results should be confirmed by further prospective studies, particularly in patients in "based on treatment" studies aged <65 years old with a CHA2DS2VASc score < 2 or without a stroke background.

Comparison of oral anticoagulation by vitamin-K antagonists and non-vitamin-K antagonists for treatment of leaflet thickening after transcatheter aortic valve implantation (TAVI)

IntroductionHypoattenuated leaflet thickening (HALT), as identified by CT imaging, is not infrequent after transcatheter aortic valve implantation (TAVI). The best choice of oral anticoagulation is unknown. We compared the effectiveness of Direct Oral AntiCoagulants (DOAC) and Vitamin-K Antagonists (VKA) to resolve HALT in patients with serial CT aquisitions. MethodsA total of 46 consecutive TAVI patients in whom anticoagulation had been initiated because of HALT and who underwent follow-up CT were identified. Indication and type of anticoagulation was according to physician discretion. Patients on DOAC were compared to VKA therapy regarding resolution of HALT. ResultsMean age of the 46 patients was 80 ± 6 years (59% men), and the mean duration of anticoagulation was 156 days. Overall, 41 patients (89%) showed resolution of HALT with anticoagulation therapy, whereas HALT persisted in 5 patients (11%). Resolution of HALT was seen in 26 out of 30 (87%) patients receiving VKA and in 15 out of 16 (94%) patients receiving DOAC, respectively. Groups did not differ regarding age, cardiovascular risk factors, TAVI prosthesis type and size or duration of anticoagulation (all p > 0.05). ConclusionAnticoagulation therapy resolves leaflet thickening after TAVI in most patients. Non-Vitamin-K antagonists seem to be an effective alternative to Vitamin-K antagonists. This finding needs to be confirmed in larger prospective trials.

Characteristics of Novel Anticoagulants versus Vitamin K Antagonists in the Ventricular Mural Thrombus

Background: To describe the characteristics, treatment practices, and clinical outcomes of patients with ventricular mural thrombus (VMT), with emphasis on the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). Methods: We performed a retrospective cohort study between 2010 and 2019 in Fuwai Hospital, China. Patients with VMT newly treated with either NOACs or VKAs were included. The primary outcome was the incidence rate of thrombus resolution at 3 months. Results: We included 196 patients in total—68.9% (n = 135) were treated with VKAs while 31.1% (n = 61) were on NOACs. Patients with a medical history of heart failure (HF) (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.17 to 3.77, p = 0.013) and a lower left ventricular ejection fraction (OR 0.36, 95% CI 0.20 to 0.65, p = 0.001) had a higher thrombus resolution. At 3 months, a significant difference was observed in the thrombus resolution between the NOACs and VKAs group with or without adjustment (OR 2.61, 95% CI 1.39 to 4.89, p = 0.003; adjusted OR 2.93, 95% CI 1.51 to 5.66, p = 0.001). Further investigation revealed that in the majority of the subgroups, individuals receiving NOAC therapy had a superior thrombus resolution than those receiving VKA therapy. Conclusions: Patients with a medical history of HF or left ventricular ejection fraction &lt;30% experienced greater effectiveness in thrombus resolution. Additionally, the resolution of VMT with NOAC treatment was considerably higher than that with VKA therapy at 3 months, with or without adjusting for baseline variables. Clinical Trial Registration: This study was registered at ClinicalTrials.gov as NCT 05006677 on August 4th, 2021.

INVICTUS: Vitamin K antagonists remain the standard of care for rheumatic heart disease-associated atrial fibrillation.

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±14.6years) were followed for 3.1±1.2years 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.

Gastrointestinal Bleeding on Anticoagulant Therapy: Comparison of Patients Receiving Vitamin K Antagonists and Non-Vitamin K Oral Antagonists

Objectives: Prior studies comparing Gastrointestinal (GI) bleeding in patients receiving Vitamin-K Antagonists (VKA) and Non-Vitamin K Antagonist Oral Anticoagulants (NOAC) focused on the crude rate of GI bleeding and less on severity of such events. The aim of our study was to assess characteristics of GI bleeding in patients on VKA therapy versus NOAC therapy. Methods: Retrospective data was collected from patients hospitalized with GI bleeding at Hadassah University Medical Center between January 2010 and July 2017. Retrieved data included demographics, laboratory results, clinical outcomes and details regarding the bleeding characteristics, evaluation, treatment and hospitalization. Patients were divided into two groups – those receiving VKA and those receiving NOAC. Results: 514 patients who presented with GI bleeding were included. 439 patients were on VKA treatment and 75 on NOAC treatment. Atrial fibrillation was the indication for anticoagulation in 64% of VKA patients and in 91% of NOAC patients. The mean HAS-BLED score was the same in VKA and NOAC patient groups. Major bleeding events were seen in 38.3% of VKA patients and 30.7% of NOAC patients and life-threatening bleeding was seen in 34.4% of VKA patients and 26.7% of NOAC (p&lt;0.05). Packed red blood cell and fresh-frozen plasma transfusions were administered less in the NOAC patients as compared to the VKA patients. No statistically significant differences in length of hospitalization, re-bleeding, or mortality were seen between groups. Conclusions: GI bleeding events on NOAC therapy are less severe and use fewer hospital resources as compared to those treated with VKA.

Is there still room for warfarin after the appearance of direct oral anticoagulants?

After the appearance of direct oral anticoagulants (DOAC), the use of vitamin K antagonists (VKA) has become more rare, but nevertheless, there are diseases in which they remain indispensable drugs. This review is devoted to VKA and the diseases in which these drugs can be used. The article compares the mechanism of action of VKA and DOAC, discusses methods of monitoring VKA therapy. Among the diseases of non-alternative use of VKA, mechanical prosthetic heart valves, atrial fibrillation in patients with moderate and severe mitral stenosis, antiphospholipid syndrome should be mentioned. Another indication for the appointment of anticoagulants is thrombosis of the left ventricle. In patients who have survived a myocardial infarction complicated by left ventricular thrombosis, anticoagulant treatment should be continued for up to 6 months with repeated imaging control. For this purpose, warfarin is successfully used. Currently, there is insufficient data to recommend the routine use of DOAC in patients with KrCl less than 25–30 ml/min, and in routine practice, warfarin remains the main anticoagulant in such patients. Direct oral anticoagulants have practically not been studied in the so-called special groups of patients: patients with congenital thrombophilia and rare localizations of thrombosis. There were practically no such patients in randomized trials and very little is known about the effectiveness of DOAC, so today warfarin remains the main drug for their treatment. Despite the fact that DOAC has displaced VKA in patients with non-valvular AF, we should not forget that it is VKA that we are obliged to prove the effectiveness of anticoagulants in patients with AF. The article discusses the pharmacogenetics of warfarin in relation to the data of the Russian Federation, as well as the practically important question of the possibility of resuming anticoagulants in patients with bleeding, the results of their own research are presented.

THE CHALLENGES OF CHRONIC ANTICOAGULATION IN PATIENTS WITH PROSTHETIC HEART VALVES

The vitamin K antagonists (VKA) had been the sole option to reduce or prevent the mechanical prosthetic valve thrombosis and thromboembolic phenomena for last several decades. Their chronic usage can lead to both bleeding as well as thrombotic complications. As the therapeutic window for the drug levels is very narrow, VKA therapy needs close monitoring and periodic blood testing (PT-INR). Patients have to follow bothersome diet restrictions. Patient-education and co-operation are paramount for maintaining the INR in the prescribed safe range. The recommendation for bridging therapy when the patients with mechanical valves are subjected to any procedure or surgery is not standardized and such instructions are often confusing to patients, family members and ill-trained health professionals. The management of special populations such as the pregnant and the elderly continue to be very challenging. Anticoagulation is generally avoided in those with bioprosthetic valves unless there is atrial fibrillation. An early clinical trial with rivaroxaban in patients with bioprosthetic valves and atrial fibrillation (RIVER trial) proved it to be non-inferior to warfarin. The role of newer oral anticoagulants in patients with prosthetic valves is the current focus of research. With large number undergoing transcutaneous aortic valve implantation (TAVI) which is a bioprosthetic device, deciding what constitutes the optimal anticoagulant for them has become an emerging clinical challenge.