Direct Oral Anticoagulants In Patients Research Articles

Tolerability of Direct Oral Anticoagulants and Low Molecular Weight Heparin in Patients with Brain Tumors or CNS Metastases

Background: Despite the increase in the use of direct oral anticoagulants (DOACs) for cancer-associated thrombosis, limited data exists regarding the safety of DOACs in patients with brain metastases or primary brain tumors. The purpose of this retrospective cohort study is to describe overall tolerability of DOACs compared to low-molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) or for stroke prevention in atrial fibrillation (AF), in patients with brain tumors or CNS metastases. Methods: This is a single center, institutional review board approved retrospective cohort study at New York University Langone Health of patients with primary brain tumors or CNS metastasis that received therapeutic dosed anticoagulation with either a DOAC or LMWH (enoxaparin) between December 1, 2018 and August 19, 2022. Electronic medical records were reviewed for pertinent data. The primary outcome was tolerability of anticoagulation, which included continuation of initial anticoagulation therapy and absence of any switches in anticoagulation, dose adjustments or temporary interruptions. Reasons for discontinuations included bleeding events, intolerance/patient preference (such as the need for subcutaneous administration or cost of therapy), provider preference, or a change in clinical status such as transition to hospice or unable to determine based on chart review. Secondary outcomes included the incidence of anticoagulation discontinuations secondary to an intracerebral hemorrhage (ICH). Results: A total of 153 patients were included (DOAC n = 105, 69%; enoxaparin n = 48, 31%). The study population was predominantly White (74%), male (59%), with a median BMI≥30 kg/m2 in 40% of the cohort and age of 65 (IQR 56-73) years; however, the enoxaparin group was younger than the DOAC group at 59.5 years vs. 67 years (p <0.001), respectively at the time of anticoagulation initiation. Primary brain tumors were the most prevalent in the total cohort at 89%, with enoxaparin most commonly prescribed at 71% versus a DOAC at 47%, p = 0.005. Other primary malignancies included anaplastic astrocytoma, glioma, anaplastic oligodendroglioma, and tanycytic ependymoma. Non-small cell lung cancer was the most common malignancy that resulted in CNS metastasis (7.2%). The most common indication for anticoagulation was for the treatment of VTE at 70%, followed by stroke prevention in AF at 28%, with the remainder 2% as off-label. The primary outcome of remaining on initial anticoagulant chosen without any anticoagulant therapy changes occurred in only 52% of the cohort. There were more changes in therapy in the enoxaparin cohort at 29, 60% vs. 44, 42% for the DOAC cohort, p = 0.033, driven by provider preference in 48% of the cohort and patient intolerance in 29% of the cohort. More patients in the enoxaparin cohort were switched to a DOAC (n = 17) and more patients in the DOAC cohort had their initial anticoagulation discontinued for non- ICH reasons (n = 14). The median time to any anticoagulation switch was 2.12 months (IQR 0.35-4.27 months). Discontinuations in patients who were still alive was primarily driven by completion of therapy, deemed by the treatment team, intolerance or patient preference, and provider preference (Table 1). Though the reason for provider preference was not always clearly elucidated upon chart review, this trend supports the movement towards increasing DOAC use. The secondary outcome of the incidence of ICH was also lower in the DOAC cohort compared to enoxaparin at 3.8 vs 14.6% (p = 0.037). (Figure 1) Conclusions: Our study demonstrates real world prescribing practice of anticoagulants for the treatment of VTE or stroke prevention in AF in patients with primary brain tumors or metastases. Although initial anticoagulants chosen were either discontinued or switched to an alternative agent, we observed a shift towards a preference for DOACs, similar to the shift towards DOACs for cancer associated thrombosis. We also observed a lower incidence of ICH with DOACs compared to LMWH. However, these results should be confirmed in a randomized controlled trial to account for the inherent selection biases we could not account for, which may have favored the initial anticoagulant chosen, the reason for switch, and overall tolerability.

Gastrointestinal bleeding with direct oral anticoagulants in patients with atrial fibrillation and anaemia

IntroductionA high risk of gastrointestinal bleeding has been reported with the use of some direct oral anticoagulants (DOACs). This risk may be of particular concern in individuals with associated anaemia. The aim of this study is to investigate potential differences in the risks of gastrointestinal bleeding and stroke among the four available DOACs in patients with atrial fibrillation (AF) and moderate or severe anaemia. Materials and methodsAll Danish patients diagnosed with incident AF who had a baseline haemoglobin measurement and subsequently initiated DOAC therapy between 2012 and 2021 were identified through administrative registries. Only patients with moderate or severe anaemia (N = 7269) were included and evaluated regarding the risk of hospitalization for gastrointestinal bleeding and stroke. Standardized absolute 1-year risks of stroke and gastrointestinal bleeding were calculated from multivariable Cox regression analyses. DOACs were compared pairwise ResultsCompared with apixaban, both dabigatran and rivaroxaban were associated with a significantly increased risk of gastrointestinal bleeding with standardized 1-year risk ratios of 1.73 (95 % confidence interval [CI], 1.10–2.35) and 1.56 (95 % CI, 1.18–1.93), respectively, while no significant difference was seen in the comparison of apixaban with edoxaban 1.32 (95 % CI, 0.41–2.32). No significant differences in gastrointestinal bleeding were observed with pairwise comparisons of dabigatran, rivaroxaban and edoxaban. Finally, no significant difference in stroke risk among the four DOACs was observed. ConclusionIn AF patients with moderate or severe anaemia, apixaban was associated with a significantly lower risk of gastrointestinal bleeding than dabigatran and rivaroxaban. No significant difference in stroke risk was observed across all four available DOACs.

PB0021 Clinical Outcomes of Direct Oral Anticoagulants in Patients with Concomitant Use of Antiepileptic Drugs in the Real-World Registry MACACOD

PB0021 Clinical Outcomes of Direct Oral Anticoagulants in Patients with Concomitant Use of Antiepileptic Drugs in the Real-World Registry MACACOD

PB0477 Safety and Efficacy of Direct Oral Anticoagulants in Patients with Chronic Thromboembolic Pulmonary Hypertension

PB0477 Safety and Efficacy of Direct Oral Anticoagulants in Patients with Chronic Thromboembolic Pulmonary Hypertension

Utilization of direct oral anticoagulants in a Saudi tertiary hospital: a retrospective cohort study.

This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital. Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence. 778 patients were included in the analysis (mean age 71.34 ± 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DOACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications. In a significant proportion of DOAC patients, the prescribed rational DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs.

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation in End-Stage Renal Disease on Hemodialysis: A Meta-Analysis of Randomized Control Trials

End-stage renal disease (ESRD) and atrial fibrillation (AF) are commonly encountered, with ESRD itself serving as a well-established risk factor for AF.1 The 2018 AF guidelines have recommended apixaban across all the spectrums of renal impairment, including patients on hemodialysis (HD), and the 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society updated guidelines have suggested careful consideration of reduced dose of direct oral anticoagulants (DOACs) in patients with ESRD.2,3 The current data on the safety and efficacy of warfarin versus DOACs in patients with AF with ESRD and HD is variable. This study aimed to perform a study-level meta-analysis to evaluate the effectiveness and safety of warfarin and DOACs in patients with AF who require dialysis.

Direct oral anticoagulants versus warfarin for the treatment of inferior vena cava thrombus.

To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in patients with inferior vena cava (IVC) thrombus. This was a single-system, retrospective cohort study of hospitalized adult patients with IVC thrombus treated with a DOAC or warfarin therapy. The primary efficacy endpoint was the thrombus resolution on imaging, and the primary safety endpoint was major bleeding, both assessed within 6 months of hospital discharge. Secondary endpoints included hospitalization for a bleeding-related event, pulmonary embolism, or death within 6 months of hospital discharge. A total of 33 patients were included in the study. Twenty-three (70%) patients received a DOAC, and 10 (30%) received warfarin. Of the 10 patients with repeat imaging available, complete resolution was noted in two (33%) DOAC patients and no warfarin patients (p = .5). Major bleeding occurred in two (8.7%) DOAC patients and one (10%) warfarin patient (p = .9). No significant differences in secondary endpoints were observed between groups. There were no differences in efficacy and safety between patients receiving DOACs or warfarin for the treatment of IVC thrombus, although results are limited by the small patient population and number of patients with repeat imaging available.

Is there a reduced confidence towards direct oral anticoagulants compared to vitamin K antagonists in patients scheduled for an elective electrical cardioversion? The results of the BLITZ-AF study

ObjectiveTo study the confidence of cardiologists in performing an electrical cardioversion in patients on oral anticoagulation (OA) with or without transoesophageal echocardiography (TOE). MethodsData about atrial fibrillation (AF) patients admitted to cardiology wards for elective cardioversion (ECV) were extrapolated from the BLITZ-AF study. Percentage of vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) and heparin prescription were analysed in relation to the use of TOE before ECV. ResultsOverall rate of TOE was 33.7% (240/713); it was used before ECV in 124/313 (39.6%) of DOACs patients and in 96/372 (25.8%) of the patients on VKAs, showing a significant reduced resort to TOE in VKAs patients (p = 0.0001). Among non-valvular patients TOE was more frequently performed in males, at younger ages and in patients on heparin when compared to patients treated with OA. TOE was also more frequently performed in tertiary hospitals and in hospitals with cardiology wards and electrophysiology labs, when compared to hospital provided only with cardiology wards. At multivariable analysis there was a significant less recourse to TOE in patients on VKAs (OR 0.47; 95% CI: 0.33–0.67) and higher recourse in the heparin group (OR: 3.85; 95% CI:1.59–9.28) with respect to patients on DOACs; a higher recourse to TOE was observed also in tertiary hospitals (OR 4.25; 95% CI 2.69–6.69) and in hospitals with cardiology wards and electrophysiology (EP) labs (OR 1.87; 95% CI 1.23–2.82). Conclusionour study shows the reluctance in cardioverting patients on DOACs respect to VKAs without a previous TOE, despite adequate anticoagulant treatment.

Replication of systematic reviews: is it to the benefit or detriment of methodological quality?

ObjectivesTo perform an overview of the overlap of systematic reviews (SRs) assessing direct oral anticoagulants and characterize these reviews in terms of bias and methodological quality (PROSPERO: CRD42022316273). Study Design and SettingA PubMed-indexed search was performed from inception to January 31, 2022 to identify SRs evaluating direct oral anticoagulants in patients treated for an acute venous thromboembolism. The risk of bias of these SRs was assessed according to the Risk Of Bias In Systematic reviews tool. Redundancy was defined as overlap in terms of the type of population considered, the interventions compared, and the studies included. ResultsA total of 144 SRs were evaluated, of which 26 (18.1%) were classified as original, 87 (60.4%) as conceptual replications, and 31 (21.5%) as excessive replications. The risk of bias was high in 19 (73.1%) of the original SRs, 65 (74.7%) of the conceptual replications, and 21 (67.7%) of the excessive replications. Compared to the original SRs, the overall methodological quality was not improved in either conceptual or excessive replications. ConclusionA large number of SRs was classified as replications; a fifth constituted excessive replications. The replications showed no improvement in overall methodological quality compared to the original SRs.

Cardiac and renal outcomes of direct oral anticoagulants in patients with atrial fibrillation.

Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin. This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death. After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin. In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF.

Antiphospholipid Syndrome: Thrombotic and Vascular Complications.

Antiphospholipid syndrome is a rare, autoimmune thrombophilia defined by vascular thrombosis and pregnancy morbidity, in the setting of documented persistent antiphospholipid antibodies including the lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I antibodies. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome, which involves widespread coagulopathy over a very short period of time. The degree of risk associated with antiphospholipid syndrome depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. The current standard treatment for unprovoked thrombosis is long-term warfarin. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin in pregnant patients. The use of direct oral anticoagulants in patients with antiphospholipid syndrome is still being debated. Their use is generally contraindicated, especially in high-risk patients, such as those with all 3 antiphospholipid antibodies present, but they may potentially be of some use in some low-risk patients.

Prescription of DOACs in Patients with Atrial Fibrillation at Different Stages of Renal Insufficiency.

Atrial fibrillation (AF) and renal insufficiency often coexist and are increasingly prevalent with advancing age. Both the risk of thromboembolic events and bleeding propensity are higher in patients with AF and impaired renal function versus those with good renal health. Direct oral anticoagulants (DOACs) are being increasingly preferred over vitamin K antagonists (VKAs) in the treatment of patients with AF and impaired renal function as VKAs may accelerate progression of chronic kidney disease. DOACs, however, are eliminated by the kidneys to varying degrees, and their dosages must be adapted in accordance with renal function. Since creatinine clearance (CrCl) monitoring is recommended in patients with AF receiving DOAC therapy, CrCl must be routinely monitored in patients at the start and during the course of anticoagulation to avoid deviation from Summary of Product Characteristics dosage specifications. This review article provides an overview of current knowledge on the selection and dose of DOACs including apixaban, dabigatran, edoxaban and rivaroxaban in AF patients at different stages of renal insufficiency, with a special focus on elderly patients with comorbidities and receiving multiple medications. The groups discussed in this review include patients with varying levels of CrCl including hyperfiltration or CrCl > 90ml/min, CrCl < 90-50ml/min, CrCl < 50-30ml/min, CrCl < 30-15ml/min and end-stage renal disease or on dialysis.

Need to determine the residual concentrations of direct oral anticoagulants in patients with atrial fibrillation undergoing transcatheter implantation of the aortic valve

Introduction. Lengthening the period of direct oral anticoagulant (DOAC) withdrawal before intervention is not allowed. Chronic kidney disease (CKD), impaired liver function, extremely low or high body mass, chronic heart failure (CHF), and age &gt; 90 years can increase blood DOAC levels. DOAC therapy does not require routine laboratory monitoring. However, there are coagulation tests that can be used to detect the presence of a drug in blood. Duration of DOAC discontinuation and the appropriateness of assessing residual anticoagulant concentrations before intervention with a high bleeding risk in a special category of patients is to be defined.Aim. To measure residual concentrations of anticoagulants and their association with perioperative bleeding risk in patients with AF using DOACs in blood samples collected immediately before TAVI.Materials and methods. The 94 patients with atrial fibrillation (AF) included in the study were characterized by senile age, a high risk of thromboembolic complication (ТС), many comorbidities, and a high prevalence of senile asthenia. The apixaban and rivaroxaban concentrations were measured according to the value of anti-Xa activity and control plasmas with normal levels of coagulation factors (Diagnostica Stago, France).Results. The median time of DOAC withdrawal before TAVI was 60 hours [47.5; 72]. However, the DOAC concentration exceeded 30 ng/ml in 1/5 patients (19.2%), and stage 3 or more CKD was more common in these patients. Our study showed the relationship between DOAC concentration and the duration of DOAC withdrawal period. However, the relationship between DOAC concentration and bleeding that occurred in the perioperative period could not be found. Patients with signs of CKD were older and had a lower BMI as compared to patients without CKD.Conclusion. Our data showed the relationship between the DOAC concentration and the duration of DOAC withdrawal period. No relationship was found between DOAC concentrations and bleeding.

The efficacy and safety of apixaban: what has changed in 12 years of its use in real clinical practice?

This review examines the position of apixaban among other direct oral anticoagulants in patients with atrial fibrillation (AF) and venous thrombosis in randomized clinical trials and real clinical practice. Since the advent of apixaban, many studies of real clinical practice (RCP) and meta-analyses have appeared. RCP studies have fully confirmed the efficacy and safety of apixaban. Now we have data that au pixaban is equally effective and safe in elderly and senile people and younger patients, as well as in patients with reduced creatinine clearance. The efficacy and safety of apixaban has been confirmed in patients with AF with the presence of diseases of several vascular basins, in patients with AF and angina, including acute coronary syndrome, treated by coronary artery stenting and conservatively. An important property of apixaban is safety, which can be traced in almost all studies, which made it possible to successfully apply it in people with a high risk of bleeding, namely in patients with active cancer and venous thrombosis. Thus, RCP studies in patients with AF, including the elderly and senile patients with chronic kidney disease, many concomitant diseases, as well as patients with VTEC, confirmed the results of randomized clinical trials of apixaban. The drug appears to be an effective and at the same time the safest anticoagulant. The safety image of Apixaban which has become noticeable in all RCTs (in patients with atrial fibrillation, VTEC, including patients with active cancer) was confirmed both in real clinical practice studies and meta-analyses, and allowed it to be successfully used in the category of patients which are at highest risk for bleeding.

Therapeutic Drug Monitoring of Direct Oral Anticoagulants in Patients with Extremely Low and High Body Weight-Pilot Study.

Phase III clinical trials for individual direct oral anticoagulants (DOACs) contained a limited representation of subjects with abnormal body weight, which were mostly limited to a BMI > 40 kg/m2, or body weight > 120 kg for obese subjects, and <50 kg for underweight subjects. Although low or high body weight is not a contraindication to DOACs therapy, it can significantly affect the safety and effectiveness of treatment. Due to the limited amount of clinical data on the use of DOACs in extremely abnormal weight ranges, optimal pharmacotherapy in this group of patients is a matter of controversy. The objective of this study was to evaluate the pharmacokinetics of DOAC properties in patients with abnormal body weight beyond the established cut-off points in the phase III studies for rivaroxaban, apixaban, and dabigatran. In total, 38 patients took DOACs for at least 12 months for non-valvular atrial fibrillation in 2019-2021. Blood samples were collected before the planned intake of the drug and 4 h after its administration. The determined concentrations of DOACs were statistically analyzed in relation to body weight, age, and eGFR (estimated Glomerular Filtration Rate). Among subjects taking apixaban, rivaroxaban, and dabigatran, the smallest representation of patients who achieved therapeutic concentrations were those treated with dabigatran. The population of people with abnormal body weight is a potential risk group of patients, in which some of them do not reach the therapeutic range of DOACs.

Factors influencing real-life use of direct oral anticoagulants in patients with cerebral sinus and venous thrombosis

BackgroundDirect oral anticoagulants (DOAC) are advocated as equally effective to vitamin K antagonists (VKA) for the treatment of patients with cerebral sinus and venous thrombosis (CSVT). However, data concerning the real-life management practices in CSVT patients are is lacking. MethodsProspective CSVT databases from four large academic medical centers were retrospectively studied. Demographics, clinical presentations, risk factors, radiological and outcome parameters were compared between CSVT patients treated with DOAC and VKA. ResultsOut of 504 CSVT patients, 43 (8.5%) were treated with DOAC, and the remaining 461 (91.5%) were treated with VKA. All patients with antiphospholipid syndrome (APLA) were treated with VKA (61 vs. 0, p=0.013). Patients with a history or presence of malignancy were also more often treated with VKA (16% vs. 5%, p=0.046). Other risk factors for thrombosis did not differ between the groups. There were no differences in clot extent or location and no differences in the percentage of favorable outcomes or mortality were observed. ConclusionOur data suggests that only malignancy and antiphospholipid antibodies significantly influenced physician's decisions towards choosing VKA rather than DOAC. DOAC appear to be as effective and safe as VKA in patients with CSVT.

Safety and efficacy of direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) remains an underdiagnosed disease. Anticoagulation is essential in its therapy to prevent recurrent venous thromboembolism (VTE). According to some international guidelines, vitamin K antagonists (VKA) remain the gold standard. Nevertheless, direct oral anticoagulants (DOAC) are widely used, partly because of numerous advantages. The objective of this study was to determine if DOAC is an effective and safe alternative to VKA in CTEPH patients. Materials and methodsA retrospective observational study was conducted between 2001 and 2021 in a CTEPH Clinic of a tertiary care hospital. We recorded demographic characteristics, anticoagulant therapies and pulmonary hypertension treatments received. Safety outcomes were bleeding events and deaths while efficacy outcomes were recurrent VTE events. ResultsAmong the study population (N = 205), the distribution of anticoagulant used transitioned from majority on VKA to majority on DOAC. In 2020, 23 (19 %) were on VKA and 97 (78 %) on DOAC. Among 11 VTE events occurring during follow-up, 7 were in the VKA group (1.10 %/person-year) and 1 in the DOAC group (0.32 %/person-year). Rates of VTE recurrence were not significantly different in those treated with DOAC compared to VKA (P = 0.21). Total bleeding rate on VKA (2.52 %/person-year) and DOAC (2.52 %/person-year) were the same (P = 1.00). Among 27 patients who died, no deaths occurred as a consequence of bleeding or VTE events. ConclusionBleeding and VTE events were not higher in CTEPH patients receiving DOAC compared to VKA which adds confidence to considering DOAC as an effective and safe alternative for long term anticoagulation in CTEPH patients.

Medium-term and long-term renal function changes with direct oral anticoagulants in elderly patients with atrial fibrillation.

Objective: Atrial Fibrillation (AF) and chronic kidney disease frequently coexist in the elderly. Warfarin-like drugs (WLDs) may be associated with a relatively greater decrease of estimated glomerular filtration rate (eGFR) as compared to direct oral anticoagulants (DOACs), but there is no evidence on the medium- and long-term changes. To further elucidate this issue in elderly patients with AF, we investigated the renal function deterioration in the two groups of the study (DOACs or WLDs). Patients and Methods: A total of 420 AF patients were enrolled (mean age: 77.0 ± 6.0 years; 136 on WLDs and 284 on DOACs). These patients underwent three eGFR measurements during the follow-up period. The between-arms difference of eGFR decline over time was investigated by Linear Mixed Models and group-based trajectory model analyses. Results: In the whole study cohort, after a median follow-up of 4.9 years (interquartile range: 2.7-7.0 years), eGFR decreased from 67.4 ± 18.2 to 47.1 ± 14.3mL/min/1.73m2 (p < 0.001). Remarkably, patients on DOACs experienced a significantly smaller eGFR decline than WLDs patients (-21.3% vs. -45.1%, p < 0.001) and this was true both in the medium-term (-6.6 vs. -19.9mL/min/1.73m2) and in the long-term (-13.5 versus -34.2mL/min/1.73m2) period. After stratification into five subgroups according to trajectories of renal function decline over time, logistic regression showed that DOACs patients had from 3.03 to 4.24-fold greater likelihood to belong to the trajectory with less marked eGFR decline over time than WLDs patients. Conclusion: Elderly patients with AF on treatment with DOACs had a relatively smaller decline of eGFR over time compared to those on treatment with WLDs. This is consistent with what was partly reported in the literature.

Should direct oral anticoagulants be used to treat protein C or S deficiency?

Few studies have evaluated the use of direct oral anticoagulants (DOACs) in patients with major thrombophilias, such as protein C or S deficiency. The data related to use of DOACs in treating protein C or S deficiency are heterogeneous, consisting of various DOACs, inconsistent ranges of dosing, dissimilar patient demographics, and inconsistent clinical endpoints. Vitamin K antagonists and low-molecular-weight heparins are preferred until more robust data are available about using DOACs in patients with protein C or S deficiency.