Role of heparin prophylaxis at different doses in patients with COVID-19 and respiratory failure: a systematic review and meta-analysis

Abstract Background Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The use of heparin at higher doses than prophylactic is advocated, but the optimal regimens remain unknown due to the balance between prevention of thromboembolic events and bleeding risks. Objective To systematically review and perform a meta-analysis aimed at evaluating the risk of VTE and of major bleeding (MB) in patients with respiratory failure due to COVID-19 according to heparin doses. Methods We performed a systematic search in MEDLINE up until 22 March 2021. Studies on patients with respiratory failure due to COVID-19 were included if reported on study outcomes according to standard prophylactic and to higher heparin doses and included more than 10 patients. Study primary outcome was VTE; secondary outcomes were MB, all-cause death, fatal bleeding and fatal pulmonary embolism (PE). Results Overall, 2 randomized and 16 observational studies were selected (3458 patients). In 13 studies (2492 patients) VTE events were similar in patients receiving standard prophylaxis or higher heparin doses (RR 1.06, 95% CI 0.58–1.95, I2 87%; only randomized studies RR 1.72, 95% CI 0.78–3.81, I2 54%). 16 studies (3174) reporting on MB and showed a significant reduction in favor of standard heparin prophylaxis (RR 0.39, 95% CI 0.28–0.53, I2 8%). No differences were observed for overall mortality according to heparin doses (RR 1.11, 95% CI 0.88–1.40, I2 68%; in 8 studies, 2448 patients). Similarly, no differences were observed for fatal bleedings and fatal PEs. In the subanalysis of studies reporting only on intensive care unit patients (ICU) an increase in the risk of VTE (RR 1.86, 95% CI 1.28–2.72, I2 18%) and a reduction on the risk of MB (RR 0.60, 95% CI 0.40–0.90, I2 0%) were observed in patients receiving standard heparin doses compared to higher doses. Overall mortality was similar (RR 1.09, 95% CI 0.86–1.39, I2 64%). Conclusion Different doses of heparin prophylaxis seem to not affect the risk of VTE in the overall patients with COVID-19 and respiratory failure. In studies reporting only on ICU patients the risk of VTE was lower when higher heparin doses were used compared to standard doses, but with no advantage in overall death and with an increase of MBs. Funding Acknowledgement Type of funding sources: None

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Computed tomography to assess risk of death in acute pulmonary embolism : a meta-analysis

The aim of this study was to evaluate whether right ventricle dilation at computed tomography (CT) angiography can be used to assess the risk of death in patients with acute pulmonary embolism. Medline and EMBASE were searched up to April 30, 2013. Studies reporting on the association between right ventricle dilation (right-to-left ventricle diameter) or dysfunction (inter-ventricular septal bowing) at CT angiography and death at 30 days, as well as at 3 months in patients with acute pulmonary embolism, were included in a systematic review and meta-analysis. CT-detected right ventricle dilation was associated with an increased 30 day-mortality in all-comers with pulmonary embolism (OR 2.08 (95% CI 1.63-2.66); p0.00001) and in haemodynamically stable patients (OR 1.64 (95% CI 1.06-2.52); p=0.03), as well as with death due to pulmonary embolism (OR 7.35 (95% CI 3.59-15.09); p0.00001). An association between right ventricle dilation and 3-month mortality was also observed (OR 4.65 (95% CI 1.79-12.07); p=0.002). Right-to-left ventricle dilation as assessed by CT angiography can be used to evaluate risk of death in all-comers with pulmonary embolism and in haemodynamically stable patients

Prognostic role of embolic burden assessed at computed tomography angiography in patients with acute pulmonary embolism : systematic review and meta-analysis

Summary: Background: In patients with acute pulmonary embolism (PE), risk stratification is indicated for tailoring of both diagnostic strategies and acute treatment. Whether embolic burden assessed at computed tomography (CT) angiography has a role in risk stratification in these patients is debated. Objective: To systematically review and perform a meta-analysis to evaluate the role of CT-assessed burden associated with embolic obstruction and embolic localization in the prognostic stratification of patients with acute PE. Methods: We performed a systematic search in EMBASE and MEDLINE up until 30 June 2013. Studies reporting on the 30-day outcome of patients with confirmed PE and CT-assessed embolic burden were included. The study outcome was death. Results: Thirty studies reporting on the prognostic value of CT-assessed embolic burden met the inclusion criteria for this systematic review; of these, 19 were included in the meta-analysis. Five studies (2215 patients) were included in the analysis of localization: an association between embolus localization in the central arteries and 30-day mortality was found after heterogeneity was resolved (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.29-3.89, I2 = 0%). No correlation was observed between obstruction index (according to the Qanadli scoring system) and 30-day mortality after heterogeneity was reduced (16 studies, 3884 patients, OR 1.22, 95% CI 0.99-1.51, I2 = 27%). Conclusion: Localization of emboli assessed at CT angiography can be used for risk stratification in patients with acute PE. Moreover, no correlation was observed between obstruction index and prognosis

Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio Study

Background-Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study. Methods \ue2The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population. Results \ue2Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin. Conclusion \ue2Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer

Bleeding with Apixaban and Dalteparin in Patients with Cancer-Associated Venous Thromboembolism: Results from the Caravaggio Study

Background Direct oral anticoagulants are recommended for the treatment of cancer-associated thrombosis (CAT) as an alternative to low-molecular-weight heparin (LMWH), but an increased bleeding risk in patients with gastrointestinal cancer was reported. The Caravaggio study compared apixaban and dalteparin for the treatment of patients with CAT. Here we describe sites of bleeding, associated cancer sites, clinical presentation, and course of major bleeding in patients included in the Caravaggio study.Methods The Caravaggio study was a multinational, randomized, open-label, noninferiority study. Bleeding events and the severity of major bleedings were adjudicated by a committee unaware of treatment allocation using predefined criteria; for the purpose of this analysis, data were analyzed in the safety population.Results Major bleeding occurred in 22 of 576 patients on apixaban (3.8%) and in 23 of 579 patients on dalteparin (4.0%). The sites of major bleeding and their distribution according to the type of cancer were similar between the two treatment groups. Major bleeding occurred in nine patients with gastrointestinal cancer in each treatment group. The clinical presentation of major bleeding was severe or fatal in 6 patients on apixaban and in 5 patients on dalteparin, while the clinical course was severe in 5 patients on apixaban and in 7 patients on dalteparin.Conclusion Apixaban is a safe alternative to LMWH for the treatment in patients with CAT. No excess in gastrointestinal bleeding was observed in patients who received apixaban, including those with gastrointestinal cancer.Thrombosis and Hemostasi