Practical Recommendations for Optimal Thromboprophylaxis in Patients with COVID-19: A Consensus Statement Based on Available Clinical Trials.

Coronavirus disease 2019 (COVID-19) has been shown to be strongly associated with increased risk for venous thromboembolism events (VTE) mainly in the inpatient but also in the outpatient setting. Pharmacologic thromboprophylaxis has been shown to offer significant benefits in terms of reducing not only VTE events but also mortality, especially in acutely ill patients with COVID-19. Although the main source of evidence is derived from observational studies with several limitations, thromboprophylaxis is currently recommended for all hospitalized patients with acceptable bleeding risk by all national and international guidelines. Recently, high quality data from randomized controlled trials (RCTs) further support the role of thromboprophylaxis and provide insights into the optimal thromboprophylaxis strategy. The aim of this statement is to systematically review all the available evidence derived from RCTs regarding thromboprophylaxis strategies in patients with COVID-19 in different settings (either inpatient or outpatient) and provide evidence-based guidance to practical questions in everyday clinical practice. Clinical questions accompanied by practical recommendations are provided based on data derived from 20 RCTs that were identified and included in the present study. Overall, the main conclusions are: (i) thromboprophylaxis should be administered in all hospitalized patients with COVID-19, (ii) an optimal dose of inpatient thromboprophylaxis is dependent upon the severity of COVID-19, (iii) thromboprophylaxis should be administered on an individualized basis in post-discharge patients with COVID-19 with high thrombotic risk, and (iv) thromboprophylaxis should not be routinely administered in outpatients. Changes regarding the dominant SARS-CoV-2 variants, the wide immunization status (increasing rates of vaccination and reinfections), and the availability of antiviral therapies and monoclonal antibodies might affect the characteristics of patients with COVID-19; thus, future studies will inform us about the thrombotic risk and the optimal therapeutic strategies for these patients

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Dabigatran Added to Dual Antiplatelet Therapy to Treat a Left Ventricular Thrombus in an 87 Year Old Patient With Myocardial Infarction and Very High Bleeding Risk

Background: A left ventricular (LV) thrombus is detected in approximately 5–10% of patients after myocardial infarction (MI). If left untreated, these LV thrombi carry a significant risk of complications including embolic stroke. According to current guidelines, anticoagulation with vitamin K antagonists (VKA) is recommended to treat a LV thrombus.Case presentation: An 87 year old patient was referred to our department with non ST-elevation MI. Five months before, he had been diagnosed with a subacute ST elevation MI, which had been treated conservatively. Recently, a rectal neoplasia had been diagnosed, but not operated yet. The patient underwent coronary angiography with implantation of two drug eluting stents (Cre8) requiring dual antiplatelet therapy. During ventriculography an apical LV thrombus of 16 mm diameter was detected. Due to the high bleeding risk in this patient, VKA therapy with potentially fluctuating international normalized ratio (INR) values was considered unsuitable. Therefore, dabigatran at a dose of 110 mg bid was chosen as anticoagulation therapy. After 4 weeks, cardiac computed tomography was performed, which failed to detect the LV thrombus described previously. Notably, triple therapy with dabigatran, clopidogrel, and aspirin was well tolerated without evidence for bleeding. The surgical resection of the rectal neoplasm was performed 2 months later without bleeding complications.Discussion: Anticoagulation is effective in patients with MI and a LV thrombus in reducing the risk of embolization and in dissolving the thrombus. Our case is complex due to the required triple therapy, very old age and significant bleeding risk of our patient due to the rectal neoplasia. Although only few reports are available for the use of non VKA oral anticoagulants (NOAC) in this indication, we chose dabigatran at a dose of 110 mg bid added to dual antiplatelet therapy for our patient. Besides the advantage of a predictable pharmacokinetic profile of NOAC in contrast to VKA, the effect of dabigatran can rapidly be reversed by idaruzicumab in the case of severe bleeding.Conclusion remarks: Physicians should carefully weigh the risk of thromboembolic events versus the risk of bleeding when combining antiplatelet with anticoagulation therapy

NGAL Correlates with Femoral and Carotid Plaque Volume Assessed by Sonographic 3D Plaque Volumetry

Background/Objectives: Inflammation represents a cornerstone in the development of atherosclerosis and early detection is essential to avoid cardiovascular events. Biomarkers like interleukin-1 beta, interleukin-6, or high sensitivity CRP (hs-CRP) have been investigated intensively in this field. Since they have several limitations, additional biomarkers are needed for cardiovascular risk stratification. The acute phase protein, neutrophil gelatinase-associated lipocalin (NGAL), modulates inflammation and is elevated in cardiovascular disease (CVD). Moreover, it contributes to plaque destabilization. Methods: In this prospective, single-center study, we included 323 asymptomatic patients with at least one cardiovascular risk factor or established CVD. NGAL levels were measured in plasma samples using a commercially available ELISA. Carotid, femoral, and total atherosclerotic plaque volumes (PV) were measured using a 3D ultrasound system (Philips iU22). Patients were separated into a low (n = 243) and high (n = 80) total PV group. Results: NGAL was significantly higher in patients with high total PV versus patients with low total PV. The NGAL amplitude for the prediction of high total PV was significantly higher when compared with hs-CRP. A high predictive value could also be observed for patients without established CVD. Conclusion: NGAL seems to be a promising biomarker for the identification of asymptomatic patients with atherosclerotic disease

Influence of Traditional Cardiovascular Risk Factors on Carotid and Femoral Atherosclerotic Plaque Volume as Measured by Three-Dimensional Ultrasound

Background: Atherosclerosis is a systemic multifocal disease with a preference for the branching points of the arteries. In this study, we quantitatively measured carotid and femoral plaque volume in subjects with cardiovascular risk factors (CVRF) and/or established atherosclerotic disease using a 3D ultrasound technique. Methods: In this prospective, single-centre study, we included 404 patients (median age 64; 56.9% men) with at least one CVRF or established cardiovascular disease. Plaque volume was measured using 3D ultrasound equipped with an automated software. Results: We found a strong correlation of plaque volume with CVRF and the number of vascular beds involved. The strongest associations with total and femoral plaque volume were noted for smoking, hypertension, age, as well as for the presence of peripheral arterial occlusive disease (p < 0.05). Carotid plaque volume was best predicted by hyperlipidaemia, hypertension, age, as well as the presence of cerebrovascular disease and coronary artery disease (p < 0.05). Conclusion: We conclude that smoking appears to be associated with total and femoral plaque volume, whereas hyperlipidaemia seems to be associated with carotid plaque volume. Measurement of 3D plaque volume is a practical and reproducible technique with the potential to become an additional screening tool in cardiovascular risk stratification