Efficacy and safety of two heparin regimens for prevention of venous thromboembolism in hospitalized patients with COVID-19: a meta-analysis.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The optimal heparin regimen remains unknown and should balance thromboembolic and bleeding risks. The aim of this study was to evaluate the efficacy and safety of standard or higher heparin regimens for the prevention of VTE in patients hospitalized due to COVID-19. We performed a systematic literature search; studies reporting on hospitalized patients with COVID-19 who received standard heparin prophylaxis vs. high (intermediate or therapeutic) heparin regimens were included if outcome events were reported by treatment group and more than 10 patients were included. Primary study outcome was in-hospital VTE. Secondary study outcomes were major bleeding (MB), all-cause death, fatal bleeding and fatal pulmonary embolism. Overall, 33 studies (11,387 patients) were included. Venous thromboembolic events occurred in 5.2% and in 8.2% of patients who received heparin prophylaxis with at high-dose or standard-dose, respectively (RR 0.71, 95% CI 0.55-0.90, I2 48.8%). MB was significantly higher in patients who received high- compared to the standard-dose (4.2% vs 2.2%, RR 1.94, 95% CI 1.47-2.56, I2 18.1%). Sub-analyses showed a slight benefit associated with high-dose heparin in patients admitted to non-intensive care unit (ICU) but not in those to ICU. No significant differences were observed for mortality outcomes. Heparin prophylaxis at high-dose reduces the risk of VTE, but increased the risk of MB compared to the standard-dose. No clinical benefit for heparin high-dose was observed for ICU setting, but its role in the non-ICU deserves further evaluation. PROSPERO registration number: CRD42021252550.

Effectiveness and safety of extended thromboprophylaxis in post-discharge patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The effect of extended thromboprophylaxis in improving the prognosis of adult patients with coronavirus disease 2019 (COVID-19) after discharge remains debatable. This meta-analysis was aimed to determine the advantages and disadvantages of extended thromboprophylaxis in these patients. METHODS: Different databases such as PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies that evaluated the effects of extended thromboprophylaxis in post-discharge patients with COVID-19 until 13 June 2022. The primary efficacy outcome was defined by the composite outcome of thromboembolism and all-cause mortality, and the safety outcome was defined by bleeding events. The odds ratios (ORs) and 95 % confidence intervals (CIs) of efficacy and safety outcomes were calculated using fixed- or random-effects model. Interaction analysis was performed to assess and compare observational studies and randomised controlled trials (RCTs). A sensitivity analysis was performed after excluding studies of poor quality. RESULTS: Eight studies involving 10,148 patients were included. The results confirmed that extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, was significantly associated with reduced composite outcome in high-risk post-discharge patients with COVID-19 (OR: 0.52; 95 % CI: 0.41-0.67, P = 0.000). Interaction analysis revealed that the effect estimates were consistent between the RCT and observational studies (Pinteraction = 0.310). Furthermore, extended thromboprophylaxis did not increase the risk of major bleeding events (OR: 1.64; 95 % CI: 0.95-2.82, P = 0.075). CONCLUSION: In post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, can significantly reduce the risk of thrombosis and all-cause mortality without increasing the risk of major bleeding events. REGISTRATION: PROSPERO CRD42022339399.

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Introduction and purpose: Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. Methods: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. Results: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p = 0.003; 52 (34.4%) vs 35 (23.2%), p = 0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. Conclusions: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.

Antecedentes y objetivos: La fibrilación auricular (FA) es frecuente en pacientes ingresados por COVID-19 grave. Sin embargo, los datos sobre el manejo de la anticoagulación crónica en estos pacientes son escasos. Analizamos la anticoagulación y la incidencia de episodios cardiovasculares mayores en pacientes con FA ingresados por la COVID-19. Métodos: Retrospectivamente, se identificaron todos los pacientes con FA ingresados por la COVID-19 entre marzo y mayo de 2020, en 9 hospitales españoles. Se seleccionó un grupo control de pacientes ingresados consecutivamente por la COVID-19 sin FA. Se compararon las características basales, incidencia de hemorragias mayores, episodios trombóticos y mortalidad. Para reducir potenciales factores de confusión se realizó un emparejamiento por puntuación de propensión, así como un análisis multivariante para predecir hemorragia mayor y mortalidad. Resultados: Se incluyeron 305 pacientes con FA ingresados por la COVID-19. Tras el emparejamiento por puntuación de propensión, 151 pacientes con FA fueron emparejados con 151 controles. Durante el ingreso, la heparina de bajo peso molecular fue el principal anticoagulante y la incidencia de hemorragia mayor y mortalidad fue mayor en el grupo de FA (16[10,6%] vs. 3[2%], p = 0,003; 52[34,4%] vs. 35[23,2%], p = 0,03, respectivamente). El análisis multivariante demostró la presencia de FA como predictor independiente de sangrados y mortalidad intrahospitalaria en los pacientes con la COVID-19. En el grupo de FA, un segundo análisis multivariante identificó valores elevados de dímero-D como predictor independiente de hemorragia mayor intrahospitalaria. Conclusiones: Los pacientes con FA ingresados por la COVID-19 representan una población de alto riesgo de sangrado y mortalidad durante el ingreso. Parece recomendable individualizar la anticoagulación durante el ingreso, considerando el riesgo específico de sangrado y trombosis.

Systematic Review and Meta-Analysis: Can We Compare Direct Oral Anticoagulants to Warfarin in Patients With Atrial Fibrillation and Bio-Prosthetic Valves?

Background There are no clear consensus guidelines on the indications and types of anticoagulation therapies in patients with bio-prosthetic valves either with concomitant atrial fibrillation (AF) or sinus rhythm. In our meta-analysis, we assessed the safety and efficacy of DOACs as compared to the standard treatment with warfarin in patients with AF and bioprosthetic valves. Methods We included randomized controlled trials (RCTs), cohort studies in the English language, and studies reporting patients with valvular heart disease that included bioprosthetic valvular disease. A systematic literature review using Embase, PubMed, and Web of Science was performed using the terms "Direct Acting Oral Anticoagulant," "Oral Anticoagulants," "Non-Vitamin K Antagonist Oral Anticoagulant," "Atrial Fibrillation," "Bioprosthetic Valve" for literature published prior to January 2021. Extraction of data from included studies was carried out independently by three reviewers from Covidence. We assessed the methodical rigor of the included studies using the modified Downs and Black checklist. Results Four RCTs and one observational study (n=1776) were included in our study. A random-effect model using RevMan (version 5.4; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen) was used for data analysis. The pooled data showed that there was a non-significant reduction in the incidence of stroke and systemic embolism in the patients taking DOACs as compared to warfarin (HR 0.69; 95% CI, 0.29, 1.67; I2 = 50%). The incidence of major bleeding was lower in the DOACs group; the difference was statistically significant (HR 0.42; 95% CI, 0.26, 0.67; I2 = 7%). The difference was not statistically significant for all-cause mortality in both groups (HR 1.24; 95% CI, 0.91, 1.67; I2 = 0%). Conclusion Our results showed that there was no difference in the outcomes of stroke and systemic embolism between DOACs and warfarin but there were statistically significantly lower major bleeding events. We conclude that larger clinical trials are needed to assess the true safety and efficacy of DOACs in patients with AF and bioprosthetic valves.

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

INTRODUCTION AND PURPOSE: Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. METHODS: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. RESULTS: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p=0.003; 52 (34.4%) vs 35 (23.2%), p=0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. CONCLUSIONS: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.

Current Opinion on the use of Direct Oral Anticoagulants for the Prophylaxis of Venous Thromboembolism among Medical Inpatients.

Venous thromboembolism (VTE) is a known cause of morbidity and mortality, especially among acutely ill medical patients. Although VTE prophylaxis is part of post-discharge clinical care in surgical patients, there is controversy regarding its use in acutely ill medical patients and the current guideline statements suggest against its routine use. Recent clinical trials (APEX, MAGELLAN and MARINER) compared the safety and efficacy of direct oral anticoagulants (including betrixaban and rivaroxaban) with the standard of the care, enoxaparin, to identify the risk-benefit tradeoff. In this review, we summarized the key findings from these trials and substudies and recent updates in society guidelines regarding VTE prevention. In addition, we discussed the potential barriers, cost-effectiveness, and COVID-19 with respect to the implementation of extended-duration or post-discharge usage of direct oral anticoagulants.