Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

Left Ventricular Thrombosis: Current Perspective and Use of Direct Oral Anticoagulants br

Left ventricular thrombus (LVT) is a serious risk factor for systemic embolism development. Despite the evident danger of this condition, currentguidelines describe management of patients with this potentially fatal complication very briefly. LVT can complicate myocardial infarction where its in-cidence is around 10%, as well as various forms of cardiomyopathies and novel coronavirus infection. According to clinical guidelines vitamin K antag-onists (VKAs) should be used as treatment of choice for thrombus resolution. However, experts point out that this therapy lacks necessary evidentialbase and bears certain difficulties because of pharmacokinetic and pharmacodynamical properties of VKAs. These drawbacks are absent in direct oralanticoagulants (DOACs), the possibility of using which in LVT is being actively studied. As for now, published results of 3 randomised clinical trialshave demonstrated similar safety and efficacy profiles of DOACs and VKAs. Similarly, the majority of retrospective cohort studies did not observesignificant differences between two groups, where some of them have shown superiority of DOACs especially in terms of earlier thrombus resolution.Nevertheless, some studies have found DOACs ineffective and even potentially unsafe regarding systemic embolism. Existing data does not allow toform an unambiguous conclusion about the equivalence of DOACs and VKAs for LVT resolution. Large randomised clinical trials are needed todetermine efficacy and safety of such treatment in these patients.

Give full play to the role of pharmacists in the safety management of direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are recommended as first-line therapy in patients with atrial fibrillation and venous thromboembolic diseases in relevant guidelines at home and abroad. Compared with warfarin, DOACs have relatively fixed dose, fewer drug interactions, and no need of routine therapeutic drug monitoring in clinic. DOACs bring much convenience to anticoagulant therapy, but they also raise a series of new medication safety challenges. Pharmacists should ensure the safe use of DOAC through improving corresponding pharmaceutical care mechanism, such as assisting doctors to improve the suitability of dose in prescription, standardizing laboratory monitoring process, setting up early warning of potential drug interaction, and strengthening anticoagulant conversion and perioperative anticoagulant therapy management. In the post-coronavirus disease 2019 era, incorporating DOACs into the standardized manage- ment at anticoagulation clinics is an important work extension of the traditional anticoagulation clinics and may reduce the risk of exposure to the novel coronavirus. In addition, considering the limit in labour and work energy of clinical pharmacists, the application of DOAC-related clinical decision support system may help improve the appropriateness of prescription and reduce the adverse drug events.Copyright © 2020 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Analysis of Pharmacy Cardiac Optimization Clinic for Patients with New Onset Atrial Fibrillation Detected via Cardiac Implantable Electronic Device Clinic.

For patients with cardiac implantable electronic devices (CIEDs), arrythmias such as atrial fibrillation (AF) can be detected and actions taken to rapidly assess and initiate treatment where appropriate. Actions include timely initiation of anticoagulation, review of blood pressure, and optimization of cholesterol/lipids to prevent unfavorable outcomes, such as stroke and other cardiovascular complications. Delays to initiating anticoagulation can have devastating consequences. We sought to implement a virtual clinic, where a pharmacist reviews patient referrals from a CIED clinic after detecting AF from the CIED. Anticoagulation choice is determined by patient-specific factors, and a shared patient-provider decision to start oral anticoagulation is made. In addition, blood pressure readings and medications are assessed with lipid-lowering therapies for optimization. A total of 315 patients have been admitted through this clinic and anticoagulated over a two-year span; in addition, 322 successful interventions were made for optimization of cardiac therapy. Rapid initiation of anticoagulation within five days of referral was likely to have reduced unfavorable outcomes, such as stroke and other cardiovascular optimizations, leading to improved patient outcomes.

Unexpected Pulmonary Embolism Late After Recovery from Mild COVID-19?

SARS-CoV-2 infection is associated with an increased risk of venous thromboembolism (VTE), which is common during active illness but unusual in milder cases and after healing. We describe a case of bilateral acute pulmonary embolism occurring 3 months after recovery from a paucisymptomatic SARS-CoV-2 infection. The only VTE risk factor demonstrable was a history of previous SARS-CoV-2 infection, with laboratory signs of residual low-grade inflammation. Clinicians should be aware of VTE as a potential cause of sudden dyspnoea after COVID-19 resolution, especially in the presence of persistent systemic inflammation. LEARNING POINTS: Venous thromboembolism may occur after COVID-19, even in milder SARS-CoV-2 infections and late after coronavirus clearance.Laboratory signs of systemic inflammation are clues for suspecting venous thromboembolism as a cause of sudden dyspnoea in patients with low risk scores for pulmonary embolism but with previous COVID-19 infection.

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic.

OBJECTIVE: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic. METHODS: We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis. RESULTS: The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n=102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465-5.172, p=0.004). CONCLUSIONS: Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

Direct Oral Anticoagulants for Stroke and Systemic Embolism Prevention in Patients with Left Ventricular Thrombus.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic.

Objective: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic. Methods: We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis. Results: The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n = 102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465-5.172, p = 0.004). Conclusions: Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

Introducción: Evaluar el efecto de las interacciones farmacológicas con anticoagulantes orales directos (ACOD) crónicos sobre la mortalidad en pacientes mayores con fibrilación auricular (FA) durante la pandemia de la enfermedad por coronavirus 2019 (COVID-19). Métodos: Seguimos a un total de 601 pacientes ancianos (65 años) de la cohorte NOEL-Drug Registry que fueron remitidos a una consulta externa de tercer nivel entre el 9 de marzo de 2020 y el 1 de marzo de 2021. Registramos las características clínicas y los medicamentos durante los últimos tres meses. Además, todas las interacciones medicamentosas se identificaron utilizando Lexicomp®. Finalmente, registramos retrospectivamente todos los eventos de muerte, el diagnóstico de COVID-19 y las muertes relevantes de la base de datos al final del estudio. De acuerdo con la regresión logística, realizamos un emparejamiento por puntaje de propensión (PP) para reducir el posible sesgo. Los factores asociados con la mortalidad total en los 12 meses se analizaron mediante análisis de riesgo de proporción de Cox multivariable. Resultados: La edad media (desviación estándar [DE]) fue de 74,5 (± 6,9) y la relación hombre/mujer, de 337/264. La prevalencia de mortalidad total fue del 16,9% (n = 102). Se analizaron un total de 4.472 fármacos para determinar la interacción con ACOD. El 81,8% de los pacientes mayores con FA no estaban en riesgo en términos de interacción potencial. En el modelo de riesgos proporcionales de Cox después del emparejamiento por PP, el uso previo de ACOD con interacción X clase se asoció con un riesgo de mortalidad significativamente mayor (índice de riesgo ajustado: 2,745; intervalo de confianza del 95%: 1,465-5,172; p = 0,004). Conclusión: Nuestro estudio mostró que, si bien la mayoría de los medicamentos concomitantes no tienen interacciones significativas con los ACOD, pocas interacciones farmacológicas graves contribuyen a la mortalidad en pacientes de edad avanzada con fibrilación auricular durante la pandemia.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Proportion of Patients on Warfarin Therapy Who Are Eligible for Conversion to a Direct Oral Anticoagulant in the Setting of COVID-19.

BACKGROUND: Warfarin, a commonly prescribed anticoagulant, requires frequent lab monitoring. Lab monitoring puts patients at risk of COVID-19 exposure and diverts medical resources away from health care systems. Direct oral anticoagulants (DOACs) do not require routine therapeutic monitoring and are indicated first line for nonvalvular atrial fibrillation (NVAF) stroke prevention and venous thromboembolism (VTE) prevention/treatment. OBJECTIVE: The purpose of the study was to determine the proportion of patients who qualify for DOACs and assess for predictors of qualification. METHODS: This cross-sectional study investigated patients on warfarin managed by Michigan Medicine Anticoagulation Service. Direct oral anticoagulant eligibility criteria were established using apixaban, dabigatran, and rivaroxaban package inserts. Patient eligibility was determined through chart review. The primary outcome was the proportion of patients who qualify for DOACs based on clinical factors. Predictors of DOAC qualification were assessed. RESULTS: This study included 3205 patients and found 51.8% (n = 1661) of patients qualified for DOACs. Qualifying patients were older (71.9 vs 59.4 years, P < 0.0001) with a higher CHA2DS2 VASc (3.7 vs 3.4, P < 0.0007). The primary disqualifying factor was extreme weight, high and low. Accounting for a patient's sex and referral source, age > 65 (odds ratio [OR] = 1.9, P < 0.0001) and NVAF indication (OR = 5.6, P < 0.0001) were significant predictors for DOAC qualification. CONCLUSION AND RELEVANCE: Approximately 52% of patients on warfarin were eligible for DOACs. This presents an opportunity to reduce patient exposure to health care settings and health care utilization in the setting of COVID-19. Increased costs of DOACs need to be assessed.

A Case of Renal Vein Thrombosis Associated With COVID-19 Treated With Rivaroxaban.

Renal vein thrombosis (RVT) is a rare form of deep venous thrombosis. It usually involves one or both renal veins and one of their branches. Most cases were reported in patients with nephrotic syndrome or inherited hypercoagulability syndromes. RVT can present with flank pain, hematuria, and acute kidney injury but can also present asymptomatically and be incidentally discovered on abdominal or renal imaging. The management of RVT is usually with warfarin for at least six to 12 months and periodically is continued if the patient is in the nephrotic range. Direct-acting oral anticoagulants (DOACs) have not been well studied in cases of RVT, especially in patients with coronavirus disease 2019 (COVID-19). We present a case of RVT in the setting of COVID-19 that was treated successfully with a DOAC, rivaroxaban, with complete resolution of the thrombus.

Give full play to the role of pharmacists in the safety management of direct oral anticoagulants

Direct oral anticoagulants (DOACs) are recommended as first⁃line therapy in patients with atrial fibrillation and venous thromboembolic diseases in relevant guidelines at home and abroad. Compared with warfarin, DOACs have relatively fixed dose, fewer drug interactions, and no need of routine therapeutic drug monitoring in clinic. DOACs bring much convenience to anticoagulant therapy, but they also raise a series of new medication safety challenges. Pharmacists should ensure the safe use of DOAC through improving corresponding pharmaceutical care mechanism, such as assisting doctors to improve the suitability of dose in prescription, standardizing laboratory monitoring process, setting up early warning of potential drug interaction, and strengthening anticoagulant conversion and perioperative anticoagulant therapy management. In the post⁃coronavirus disease 2019 era, incorporating DOACs into the standardized manage⁃ ment at anticoagulation clinics is an important work extension of the traditional anticoagulation clinics and may reduce the risk of exposure to the novel coronavirus. In addition, considering the limit in labour and work energy of clinical pharmacists, the application of DOAC⁃related clinical decision support system may help improve the appropriateness of prescription and reduce the adverse drug events. © 2020 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Impact of COVID-19 on the Prescribing Pattern of Oral Anticoagulants for Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. METHODS: A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. RESULTS: A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. CONCLUSION: This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis;(2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment;(3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis;(4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding;and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

Clinically Ambiguous Hemorrhagic Cardiac Tamponade Associated with Apixaban.

Hemorrhagic cardiac tamponade in the setting of direct oral anticoagulants (DOACs) is rare but life-threatening. Presentation in subacute cases can also be nonspecific, which can potentially delay diagnosis. A 60-year-old female with a history of heart failure and chronic obstructive pulmonary disease presented with shortness of breath, chest pain, and cough while on treatment with apixaban after a recent hospitalization for pulmonary embolism. Clinical presentation was consistent with multiple diagnoses, including pneumonia and heart failure exacerbation. However, there were several risk factors for hemopericardium with DOACs such as elevated creatinine, hypertension, elevated international normalized ratio (INR), and concomitant use of medications with similar metabolic pathways as apixaban. In addition, subtle findings on examination such as oximetry paradoxus and electrical alternans were crucial for an early diagnosis and management. In this case, we discuss key characteristics of hemopericardium with DOACs, as well as considerations on its management.

The Use of Oral Anticoagulation Is Not Associated With a Reduced Risk of Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P interaction = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.

An Update of the Efficacy and Comparative Characteristics of Direct (New) Oral Anticoagulants (DOACs).

Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa- direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients' physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.

Anticoagulants after Discharge in Patients with COVID-19: What we Know at the End of 2021

This review discusses reasons for prolonged use of anticoagulants after discharge of patients with COVID-19 without additional indication for anticoagulation. Data regarding rate of thrombotic and thromboembolic complications in patients with COVID-19 after discharge from the hospital are presented. Large randomized controlled trials EXCLAIM, ADOPT, MAGELLAN, APEX and MARINER with prolonged use of anticoagulants in patients hospitalized with acute nonsurgical diseases before pandemia of COVID-19 are discussed. The first prospective randomized controlled trial MICHELLE with direct oral anticoagulant rivaroxaban in a dose 10 mg once daily after discharge of patients with COVID-19 with high risk at least venous thromboembolism are analyzed. It seems that the most relevant approach for the determination of indications for prolonged use of anticoagulants in doses dedicated for primary prevention of venous thromboembolism after discharge of patients with COVID-19 without apparent indication for anticoagulation is a modified IMPROVE VTE risk score with the addition of elevated in-hospital D-dimer level. And the most well-studied approach for anticoagulation in these patients is a direct peroral anticoagulant rivaroxaban 10 mg once daily for 35 (and possibly up to 45) days after discharge. © 2021 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Dabigatran in patients with atrial fibrillation after COVID-19 hospitalization: an update of the ANIBAL protocol.

COVID-19 increases the risk of atrial fibrillation (AF) and thrombotic complications, particularly in severe cases, leading to higher mortality rates. Anticoagulation is the cornerstone to reduce thromboembolic risk in patients with AF. Considering the risk of hepatotoxicity in patients with severe COVID-19 as well as the risk of drug-drug interactions, drug-induced hepatotoxicity and bleeding, the ANIBAL protocol was developed to facilitate the anticoagulation approach at discharge after COVID-19 hospitalization. However, since the publication of the original algorithm, relevant changes have occurred. First, treatment of COVID-19 pneumonia has been modified with the use of dexamethasone or remdesivir during the first week in patients that require oxygen therapy, and of dexamethasone and/or tocilizumab or baricitinib during the second week in patients that necessitate supplementary oxygen or with a high inflammation state, respectively. On the other hand, metabolic syndrome is common in patients with AF as well as metabolic-associated fatty liver disease, and this could negatively impact the prognosis of patients with COVID-19, including high transaminase levels in patients treated with immunomodulators. The EHRA guidelines update also introduce some interesting changes in drug-drug interaction patterns with the reduction of the level of the interaction with dexamethasone, which is of paramount importance in this clinical context. Considering the new information, the protocol, named ANIBAL II, has been updated. In this new protocol, the anticoagulant of choice in patients with AF after COVID-19 hospitalization is provided according to three scenarios: with/without dexamethasone treatment at discharge and normal hepatic function, transaminases ≤2 times the upper limit of normal, or transaminases >2 times the upper limit of normal.

Rivaroxaban with Aspirin Versus Aspirin for Peripheral Arterial Disease and Intermittent Claudication. Rationale and Design of the COMPASS CLAUDICATION Trial.

BACKGROUND: The COMPASS trial demonstrated that in patients with peripheral arterial disease, the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on claudication distance. STUDY DESIGN: Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from the baseline to 24 weeks, measured by 6 min walking test and treadmill test. The primary safety outcome is the incidence of major bleeding and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria. SUMMARY: The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.