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The year 2022 marked the return of the International Society on Thrombosis and Haemostasis (ISTH) congress to an in-person format. The meeting took place at the ExCel Centre in London, UK from 9 to 13 July. Although many of the sessions were available through their online platform, ISTH 2022 saw around 6500 in-person attendees from all over the world.
A Bayer-sponsored symposium aimed to address the issue of how to protect vulnerable patients with venous thrombosis. It covered a range of patients who could be considered vulnerable, from the extremes of age and bodyweight to those with cancer or a high-risk index event such as pulmonary embolism. The symposium was chaired by Lord Ajay Kakkar, and included presentations from Dr Mandy Lauw, Professor Agnes Lee, Professor Walter Ageno and Professor Jan Beyer-Westendorf.
On Sunday at 13:15 BST, Bayer presented a sponsored symposium addressing the difficult issue of how best to manage vulnerable patients in the field of venous thrombosis. Professor The Lord Kakkar (Thrombosis Institute, London) opened the symposium by asking the audience to consider who a vulnerable patient is. He followed up by noting that, while the concept of vulnerability is often defined with reference to discrete populations, in reality it includes any patient at risk of developing thrombosis.
Lord Kakkar raised the question: who is vulnerable?
Dr Mandy Lauw (Erasmus MC, the Netherlands) was the first speaker, building her presentation around a series of patients with similar demographics and diagnoses, but with key differences that placed them in at-risk categories. Each patient case was then placed in the context of the existing literature, from the very young (EINSTEIN JUNIOR),1 to the older, frail population (EINSTEIN DVT and EINSTEIN PE).2
Dr Mandy Lauw covered vulnerability in different patient populations, from the extremes of age to those with obesity and those with renal impairment
The next speaker was Professor Agnes Lee (University of British Columbia, Canada), whose fictional patient with cancer-associated thrombosis (CAT), Miss Eliza Doolittle, faced a transformative journey throughout the course of her illness. Professor Lee placed particular emphasis on the importance of patient choice and an individualized approach to treatment in this population.
Professor Agnes Lee emphasized the importance of engaging with patients
Professor Walter Ageno (University of Insubria, Italy) followed, shifting emphasis from high-risk populations to high-risk pathology by focusing on one patient with three varying presentations of pulmonary embolism. These presentations corresponded to the risk definitions from the ESC guidelines,3 with the correct approach in each scenario varying from home treatment, even in a patient with possible vulnerable characteristics, through to a haemodynamically unstable presentation requiring systemic thrombolysis.
Professor Walter Ageno discussed the vulnerability of patients presenting with a high-risk index event
Professor Jan Beyer-Westendorf (University Hospital ‘Carl Gustav Carus’ Technical, Germany) provided the final talk, revisiting several of the previously explored patients to provide a decision-making framework for the continuation, cessation or dose-reduction of anticoagulation. A lively discussion amongst the faculty followed, covering the approach to anticoagulation extension in at-risk patients, with particular reference to the need for continuous reassessment of the benefits and potential risks of treatment. Following this, Lord Kakkar brought the symposium to a close, emphasizing how the volume of evidence we now have on direct-acting oral anticoagulants (DOACs): ‘lets us act confidently and responsibly’.
Professor Jan Beyer-Westendorf revisited several of the patient cases previously explored
The OSCAR-UK study provided further data showing that rivaroxaban is as safe and effective as LMWH in CAT
A poster on the OSCAR-UK study was presented by Dr Alexander T. Cohen as a follow-up to the data presented previously at ICTHIC on the intention-to-treat population. This present analysis was for the on-treatment population of this retrospective study of 2173 patients. The study aimed to evaluate the effectiveness and safety of rivaroxaban compared with low molecular weight heparin (LMWH) in a real-world setting in patients with CAT and to estimate discontinuation rates of both treatments. Patients with cancer types that were not endorsed for DOAC treatment by the ISTH guidelines were not included. Rivaroxaban was found to be as effective as LMWH (weighted sub-distribution hazard ratio for venous thromboembolism [VTE] recurrence at 3 months of rivaroxaban vs LMWH 0.56; 95% confidence interval [CI] 0.11–2.79; similar results were obtained at 6 and 12 months), with no significant increase in rate of bleeding events compared with LMWH (weighted sub-distribution hazard ratio for significant bleeding events at 12 months of rivaroxaban vs LMWH 1.08; 95% CI 0.55–2.14). Patients treated with rivaroxaban remained on therapy for a longer period of time compared with those on LMWH.
Cohen A et al. Comparison of effectiveness and safety of direct oral anticoagulant versus low molecular weight heparin treatment for venous thromboembolism in patients with active cancer – the OSCAR UK Study. ISTH, 9–13 July 2022. Poster PB0911
DOACs showed no over-coagulation effect in patients with a very low bodyweight
Rachel Clapham presented results from an observational study involving anticoagulation in 95 patients with very low bodyweight. The studied population was composed of patients with a total bodyweight of ≤50 kg, a group that often also had significant renal impairment# or cancer and were often elderly. Plasma trough concentrations of edoxaban, rivaroxaban and apixaban were all consistently in the reference range, and no consistent over-coagulation effect was observed.
Clapham R et al. Direct oral anticoagulant prescribing in patients with a very low bodyweight – experience from King’s College Hospital. ISTH, 9–13 July 2022. OC 62.5
The rate of bleeding events in a real-world study was consistent with those previously published, with a higher rate of bleeding in high-risk cancers
A real-world cohort of 449 patients on DOACs was split approximately evenly between those on a DOAC for CAT and for non-valvular atrial fibrillation. In general, patients were older than those in previously published CAT studies. Bleeding events were comparable with other CAT studies, but more frequent in patients with active luminal gastrointestinal/genitourinary lesions and those at risk of drug–drug interactions.
Haque F et al. Safety and efficacy of direct oral anticoagulant in elderly patients with cancer: real-world challenges. ISTH, 9–13 July 2022. Poster PB0921
*Disclaimer: Patients with malignant disease may simultaneously be at higher risk of bleeding and thrombosis. The individual benefit of antithrombotic treatment should be weighed against risk for bleeding in patients with active cancer dependent on tumour location, antineoplastic therapy and stage of disease. Tumours located in the gastrointestinal or genitourinary tract have been associated with an increased risk of bleeding during rivaroxaban therapy. In patients with malignant neoplasms at high risk of bleeding, the use of rivaroxaban is contraindicated.
#Clinical data for patients with severe renal impairment (Creatinine clearance (CrCl) 15–29 ml/min) indicated that rivaroxaban plasma concentrations are significantly increased. Therefore, Xarelto should be used with caution in these patients. Use is not recommended in patients with CrCl <15 ml/min.
Rivaroxaban was effective with no major toxicities in a pilot study in paediatric CAT
This pilot study examined a series of 77 paediatric patients with thrombosis and acute lymphoblastic leukaemia treated with LMWH for 7 days followed by body weight-adjusted 20 mg equivalent dose of rivaroxaban given for a minimum of 3 months. The treatment regimen was found to be effective, without any major toxicities noted. In children, thrombosis treatment with rivaroxaban resulted in a similarly low recurrence risk without increased bleeding, compared with standard anticoagulants. The authors also noted that rivaroxaban was affordable and easier to use than LMWH.
Rodriguez S et al. Rivaroxaban for the treatment of thrombosis in pediatric patients with leukemia. Results of a pilot study. ISTH, 9–13 July 2022. Poster PB0270
A meta-analysis found clinically relevant non-major bleeding risk was similar between patients on a VKA and a DOAC following an unprovoked VTE
Dr Faizan Khan presented a meta-analysis exploring the rate of clinically relevant non-major (CRNM) bleeding in patients who continue anticoagulation following the initial 3–6-month treatment phase for an unprovoked VTE. Although somewhat limited by the inconsistency of how CRNM bleeding is reported in clinical trials, an incidence rate of 6.48 per 100 person-years (95% CI 4.69–8.55) for patients on a VKA and 5.01 (95% CI 3.71–6.49) for patients on a DOAC was identified.
Khan F et al. Long-term risk of clinically relevant non-major bleeding during extended anticoagulation for unprovoked venous thromboembolism: A systematic review and meta-analysis. ISTH, 9–13 July 2022. OC 34.4
A report from the RIETE registry described the shifting nature of predictive risk factors of VTE recurrence or major bleeding following an unprovoked VTE
A registry study of 33,262 patients with a first episode of unprovoked VTE sought to understand the risk factors that may predict major bleeding for patients on anticoagulation and recurrent VTE after stopping anticoagulation. It was noted that risk factors appeared to be dynamic, with those that identified bleeding in the first 3 months not always proving predictive beyond that time, with a similar observation noted for VTE recurrence. Notably from their analysis, selection of a DOAC versus other treatments was not found to be a predictor of major bleeding; however, after stopping anticoagulation, previous DOAC use was found to predict recurrence (HR=1.25; 95% CI 1.01–1.55; p<0.05).
Gabara C et al. Identification of risk factors for major bleeding during anticoagulation and recurrent venous thromboembolism after its discontinuation in patients with a first unprovoked venous thromboembolism. ISTH, 9–13 July 2022. OC 34.5
Almost a quarter of VTE events occurring in the Tromsø registry study could be attributed to being overweight or obese
Dr Vania Morelli presented results from an analysis of the prospective Norwegian registry Tromsø study featuring 36,341 participants on behalf of the lead author Tobias Frischmuth. The analysis aimed to estimate the proportion of cases of VTE that could be attributed to being overweight or obese. Their estimates suggested that up to one quarter of all VTE events in the general population could be attributed to being overweight or obese; similar results were seen in VTE subgroups and analyses exploring outcomes in men, women and the elderly (≥70 years).
Frischmuth T et al. The risk of incident venous thromboembolism attributed to overweight and obesity: The Tromsø study. ISTH, 9–13 July 2022. OC 42.1
More experienced physicians were more likely to dose-reduce in VTE
Results from a survey of 171 clinicians indicated that the majority chose to use a reduced dose of a DOAC when extending treatment, with the likelihood to dose-reduce increasing with clinical experience
Woller S et al. Physician practice behaviors surrounding dose-reduction of direct oral anticoagulants for the extended phase treatment of venous thromboembolism. ISTH, 9–13 July 2022. Poster PB0466