Vitamin K Antagonists Research Articles

Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry

ObjectiveTo evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).DesignObservational cohort analysis based on a...

CytoSorb® hemoadsorption of apixaban during cardio-pulmonary bypass for heart transplantation

IntroductionHeart transplantation is an emergency surgery requiring cardio-pulmonary bypass (CPB) and its timing is unpredictable. Patients on the transplant waiting list often have multiple reasons for being anticoagulated. Direct oral anticoagulants (DOACs) such as apixaban are very popular due to their well-known advantages. Intraoperative removal of apixaban using CytoSorb® (CytoSorbents Inc., Princeton, NJ, USA), seems to be an interesting solution for patients on DOACs requiring an emergency CPB intervention. The aim of this short communication is to describe the perioperative effects of the use of the CytoSorb® hemoadsorption device during emergency CPB for a heart transplant patient Case presentationA 61-year-old male patient (75kg/173cm) wait-listed for heart transplantation was admitted to our hospital (Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France) to benefit from a heart transplantation. This patient, with many comorbidities, has an end-stage heart failure with multiple episodes of decompensation over the previous year. He was anticoagulated with a Vitamin K antagonist (VKA) due to atrial fibrillation and was switched to apixaban (5mg twice daily) 9 days before surgery based on poor clotting control. A NaCl 0.9% primed CytoSorb cartridge was inserted into the CPB circuit. Hemoadsorption was performed during the entire CPB duration. Anti-Factor Xa Activity (AFXaA) levels were taken at multiple time points before, during and after surgery in order to monitor anticoagulation. Results. Preoperatively, activated Clotting Time (ACT) was 146 seconds. The ACT reached 545 seconds after administration of 25,000IU of unfractionated heparin (UFH). Surgery consisted of an orthotopic heart transplantation with bi-caval anastomoses.CPB duration was 133 minutes with 83 minutes of aortic cross clamping. Total graft ischemic time was 249 minutes. At the time of anesthesia induction and after UFH administration, AFXaA levels were 330ng/mL and 317ng/mL, respectively. Thereafter, AFXaA decreased to 137ng/mL during CPB and to 57ng/mL after the end of CPB and 250mg (=25,000IU) of protamine administration.After surgery, AFXaA levels stabilized over 50ng/mL over the next 14 hours. Postoperative anticoagulation was performed with the use of UFH starting 6 hours after surgery.No primary graft dysfunction (PGD) was observed, and during the post-operative period of 72 hours, the patient did not have any bleeding events requiring reintervention or transfusion. ConclusionIn conclusion, we observed that CytoSorb® could be a potential solution to remove apixaban intraoperatively. If this efficacy is confirmed in larger trials, it would allow transplant candidates to be treated with DOACs without requiring a switch to VKAs.

Dental Extractions In Patients Under Vitamin-K Antagonists in Morocco

Dental Extractions In Patients Under Vitamin-K Antagonists in Morocco

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.

RARE CASE OF SPONTANEOUS HEMOPERICARDIUM IN A PATIENT RECEIVING APIXABAN: CASE REPORT

Apixaban is a new oral anticoagulant (NOAC) available since 2012, indicated particularly for the prevention of embolic events in patients with non-valvular atrial fibrillation [1]. It is a direct inhibitor of factor Xa, with a half-life of around 12 hours. This new anticoagulant is associated with a lower risk of bleeding than vitamin K antagonists (VKAs) such as warfarin and requires less monitoring [2]. However, several recently published cases have demonstrated a correlation between Apixaban and the occurrence of pericardial effusion. We report the case of a 75-year-old hypertensive man diagnosed with atrial fibrillation 3 months ago, treated with Apixaban 5mg twice daily. He presented to the emergency department with rapidly worsening dyspnea, and echocardiography revealed a large pericardial effusion requiring drainage. A full etiological work-up was carried out, revealing no underlying pathology or triggering event to explain his pericardial effusion. We believe that his recently introduced anticoagulant therapy is the true cause.

Safety of Sofosbuvir-Based Direct-Acting Antivirals for Hepatitis C Virus Infection and Direct Oral Anticoagulant Co-Administration.

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

Antithrombotic Strategies After Transcatheter Aortic Valve Replacement in Patients Without an Indication of Oral Anticoagulants: A Network Meta-Analysis of Randomized Controlled Trials.

Single-antiplatelet therapy (SAPT) has been a standard of care posttranscatheter aortic valve replacement with no clear evidence exist using direct oral anticoagulants (DOACs), vitamin K antagonists (VKA), or dual antiplatelet agents (DAPT); thus we aim to compare the safety and efficacy of the various antithrombotic strategies after transcatheter aortic valve replacement. We performed a network meta-analysis using a frequentist framework, pooling dichotomous outcomes using risk ratio (RR), and continuous data using mean difference, along with the corresponding 95% confidence interval (CI). Nine randomized controlled trials with 4193 patients were included, 567 patients were in the VKA group, 591 patients in the SAPT group, 1571 patients in the DAPT group, and 1464 patients in the DOACs group. Only DOAC showed a statistically significant higher risk of all-cause mortality [RR of 1.88 (95% CI: 1.07-3.28)] with no statistically significant difference between our arms in terms of mortality. For minor bleeding, DAPT had a significant higher risk with RR of 1.53 (95% CI: 1.04-2.25), while for major bleeding, DAPT and DOAC had a significant higher risk with RR of 2.36 (95% CI: 1.27-4.40) and 4.74 (95% CI: 2.05-10.92), respectively. There was no significant difference in terms of stroke and life-threatening bleeding. Moreover, only DOAC showed a significantly lower risk for valve thrombosis, when compared to other strategies [RR: 0.24 (95% CI: 0.13-0.46)]. Overall, SAPT had lower major bleeding events compared to other arms. There were no differences in the outcomes of stroke, myocardial infarction, or life-threatening bleeding outcomes. However, DOACs significantly reduced valve thrombosis compared to VKAs.

A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease

BackgroundPatients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. MethodsThis is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1–4 weeks, 1–6 months, 6–12 months, >1 year after start of DOAC. ResultsEleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. ConclusionsWe propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.

Long‐term cognitive function changes with non‐vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study

AbstractBackgroundAtrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.MethodsNine hundred and eighty‐three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between‐arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group‐based trajectory model analyses.ResultsIn the whole multicenter observational study, after a long follow‐up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow‐up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).ConclusionIn older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.

Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs.

The Aortic Prosthesis and Aortic Valve Bioprosthesis Trombosis as a Late Complication in Patients after the Bentall Procedure Followed by a Valve-in-Valve Transcatheter Aortic Valve Implantation.

Background: Valve-in-Valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a viable therapeutic option for structural valve degeneration following surgical aortic valve replacement (SAVR) or prior TAVI. However, the understanding of long-term complications and their management remains limited. Case presentation: We present the case of a 69-year-old male with a history of ViV-TAVI, who presented with symptoms of non-ST elevation myocardial infarction (NSTEMI) and transient ischemic attack (TIA). Computed tomography (CT) revealed thrombosis of the ascending aortic graft and aortic valve prosthesis. Transthoracic echocardiography (TTE) further confirmed new valve dysfunction, indicated by an increase in the aortic valve mean gradient. Treatment with low-molecular-weight heparin (LMWH) resulted in partial thrombus resolution. The multidisciplinary Heart Team opted against coronary angiography and recommended the long-term administration of vitamin K antagonists (VKAs). Follow-up CT showed the complete resolution of the thrombus. Conclusions: Thrombosis of the aortic graft and aortic valve following ViV-TAVI may be attributed to alterations in blood flow or mechanical manipulations during the TAVI procedure, yet it can be effectively managed with VKA therapy. CT is a valuable tool in coronary assessment in patients with NSTEMI and aortic valve and/or aortic graft thrombosis.

Dementia risk reduction between DOACs and VKAs in AF: A systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case-control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random-effects model was used to perform meta-analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83-0.93, I 2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72-0.97, I 2 = 0%); 65-74 years, HR 0.86 (95% CI 0.81-0.92, I 2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74-1.55, I 2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824-0.997, I 2 = 0%). This meta-analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype.

Clinical outcomes of patients receiving long-term fondaparinux for thrombotic antiphospholipid syndrome.

Vitamin-K antagonists (VKA) are considered the first-line anticoagulants for thrombotic antiphospholipid syndrome (TAPS), particularly with triple positivity or arterial events. However, thrombotic recurrence remains high despite anticoagulation and other clinical issues may arise. Long-term parenteral anticoagulants may therefore be considered, however little is known about the viability of fondaparinux in this setting. We describe the efficacy and safety of long-term fondaparinux for TAPS (>3-months duration) treated at a single centre in the UK. Clinical features and the outcomes of recurrence and bleeding were reviewed using electronic patient records. 46 patients were identified with history of either venous or arterial TAPS and a total 175 patient-years using fondaparinux (median duration 2.7 years/patient (IQR 1.4-4.8)). 43 (93%) had VKA as first-line anticoagulation with a median duration of 6.5 years (IQR 4.0 - 9.8). All patients received fondaparinux as second-to fourth-line anticoagulation.Thrombosis recurrence occurred in 1 (1%) patient (0.6 events/100-patient years). Major, clinically relevant non-major (CRNM) or minor bleeding occurred in 2 (7%), 5 (10.9%) and 8 (17.4%) patients respectively. Major/CRNM bleeding rates were 1.1 and 2.9 events/100-patient-years. Age >65years was associated with bleeding (p = .047) and concurrent antiplatelets were associated with major/CRNM bleeding (p = .011). Logistic regression showed increasing age was associated with bleeding (OR = 1.097, p = .009). We suggest that fondaparinux may be used for TAPS when VKA is not appropriate. Thrombotic recurrence was infrequent, and the number of major bleeding events appeared comparable to conventional therapies.

Safety and Effectiveness Outcomes between Apixaban Versus Vitamin K Antagonists in Atrial Fibrillation Patients on Dialysis.

Anticoagulant therapy for atrial fibrillation (AF) in patients with end-stage kidney disease (ESKD) undergoing dialysis poses significant challenges. This review aimed to furnish clinicians with the latest clinical outcomes associated with apixaban and vitamin K antagonists (VKAs) in managing AF patients on dialysis. Literature from the PubMed and Embase databases up to March 2024 underwent systematic scrutiny for inclusion. The results were narratively summarized. Six studies were included in this review, comprising the AXADIA-AFNET 8 study, the RENAL-AF trial, and four observational studies. In a French nationwide observational study, patients initiated on apixaban demonstrated a diminished risk of thromboembolic events (hazard ratios [HR]: 0.49; 95% confidence interval [CI]: 0.20-0.78) compared to those on VKAs. A retrospective review with a 2-year follow-up, encompassing patients with AF and ESKD on hemodialysis, evidenced no statistical difference in the risk of symptomatic bleeding and stroke between the apixaban and warfarin groups. Two retrospective studies based on the United States Renal Data System (USRDS) database both indicated no statistical difference between apixaban and VKAs in the risk of thromboembolic events. One study reported that apixaban correlated with a reduced risk of major bleeding relative to warfarin (HR: 0.72, 95% CI: 0.59-0.87), while the other study suggested that apixaban was associated with a decreased risk of mortality compared to warfarin (HR: 0.85, 95% CI: 0.78-0.92). The AXADIA-AFNET 8 study found no differences between apixaban and VKAs in safety or effectiveness outcomes for AF patients on dialysis. The RENAL-AF trial, however, was deemed inadequate for drawing conclusions due to its small sample size. Currently, the published studies generally support that apixaban exhibits non-inferior safety and effectiveness outcomes compared to VKAs for AF patients on dialysis.

Association Between Oral Anticoagulant Adherence and Serious Clinical Outcomes in Patients With Atrial Fibrillation: A Long-Term Retrospective Cohort Study.

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.

Health-Related Quality of Life and Satisfaction in Atrial Fibrillation Patients on Anticoagulant Therapy: Differences between Vitamin K Antagonists and Direct Oral Anticoagulants; Results from the Multicentre REGUEIFA Registry.

Background: Oral anticoagulation (OAC) is pivotal in the clinical management of atrial fibrillation (AF) patients. Vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) prevent thromboembolic events, but information about the quality of life (QoL) and patient satisfaction in relation with the anticoagulant treatment is limited. Methods: REGUEIFA is a prospective, observational, and multicentre study that included patients with AF treated by cardiologists. We included patients treated with VKAs or DOACs. The EuroQol-5D (EQ-5D) questionnaire evaluated QoL, and the Anti-Clot Treatment Scale (ACTS) questionnaire investigated patient satisfaction with OAC. Results: A total of 904 patients were included (532 on VKA and 372 on DOACs). A total of 846 patients completed the EQ-5D questionnaire, with results significantly worse in patients on VKAs than on DOACs: more mobility limitations (37.6% vs. 24.2%, p < 0.001), more restriction in usual activities (24.7% vs. 18.3%, p = 0.026), more pain/discomfort (31.8% vs. 24.2%, p = 0.015), a lower visual analogue scale (VAS) score (66.4 ± 16.21 vs. 70.8 ± 15.6), and a lower EQ-D5 index (0.79 ± 0.21 vs. 0.85 ± 0.2, p < 0.001). After adjusting for baseline characteristics, VKA treatment was not an independent factor towards worse EQ-5D results. Also, 738 patients completed the ACTS questionnaire, and burden and profit scores were lower in patients on VKAs than for DOACs (52.1 ± 8.4 vs. 55.5 ± 6.8, p < 0.001 and 11.1 ± 2.4 vs. 11.8 ± 2.6, p < 0.001, respectively). The negative impact score was higher for VKAs than for DOACs (1.8 ± 1.02 vs. 1.6 ± 0.99, p < 0.001), with a general positive impact score lower for VKAs than for DOACs (3.6 ± 0.96 vs. 3.8 ± 1.02, p < 0.001). Conclusions: Patients on VKA have more comorbidity and worse EQ-5D and VAS scores than those on DOACs. VKA has a greater burden and higher negative impact on the patient's life than DOACs.

Apixaban, edoxaban and rivaroxaban but not dabigatran are associated with higher mortality compared to vitamin-K antagonists: A retrospective German claims data analysis.

Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials. Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding. Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p<0.001) but not for dabigatran (p=0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p<0.001) and 13.0% for dabigatran versus 12.8% for VKA (p=0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort. In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus after Myocardial Infarction: A Meta-analysis

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

A Tool Integrated into the Electronic Health Record to Guide Proper Decision-Making Regarding Peri-Endoscopic Anticoagulant Management: A Retrospective Cohort Study.

Background-Anticoagulants, such as vitamin-K antagonists (VKA) and direct oral anticoagulants (DOAC), are widely used among patients who undergo endoscopic procedures. To balance between bleeding and thromboembolic risks, careful decisions must be made about whether and for how long anticoagulants have to be stopped peri-endoscopically and if bridging is necessary. We created a tool in the electronic health records system (EHR) HIX (Microsoft) for invasive procedures to aid this decision-making. By selecting the anticoagulant indication or thrombo-embolic risk and the bleeding risk of the procedure, the tool automatically generates advice for periprocedural anticoagulant management. Objectives-This study assesses whether the tool is used properly peri-endoscopically. Secondly, it examines how many bleeding and thromboembolic events have occurred since the implementation of the tool. Methods-This retrospective study included all orders placed for endoscopies for patients using VKA or DOAC between 2018 and 2021. Results-In total, 986 endoscopies were included for analysis. In 89%, the tool was used correctly; the main error was selecting the wrong bleeding risk (7.5%). The cumulative incidence for moderate or severe bleeding events for DOAC and VKA was 2 (0.5%) and 0, respectively. The cumulative incidence of thromboembolic events for DOAC and VKA was 1 (0.2%) for each. Conclusions-This study evaluates the use of an EHR-integrated decision-making tool to aid peri-endoscopic anticoagulant management. By analysing the usage of the tool, we formulated several suggestions to improve the tool. Although this study is not a comparative one, we can conclude that the thromboembolic and major bleeding risks were low.

Antithrombotic Strategies in Atrial Fibrillation After ACS and/or PCI: A 4-Way Comparison From AUGUSTUS

BackgroundThe optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known. ObjectivesThe authors sought to determine which antithrombotic regimen best balances safety and efficacy. MethodsAUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint. ResultsA total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death. ConclusionsIn patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)