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Hosted from Philadelphia, USA, but run as a fully virtual event, the International Society on Thrombosis and Haemostasis (ISTH) 2021 conference took place from 17 to 21 July. Over the five days, participants were treated to a wealth of presentations and discussions, which included new data in venous thromboembolism (VTE), cancer-associated thrombosis (CAT) and peripheral artery disease (PAD).
Full recordings of presentations made at the meeting are available to registered participants and can be accessed at www.isth2021live.org. Conference abstracts are freely available at abstracts.isth.org.
Bayer hosted a symposium focussed on the management of complicated cases in VTE and what can be learned from these. Each case took a ‘Past, Present, Future’ format to enable full understanding of the patient treatment journey and outcomes.
As moderator, Professor Agnes Lee opened the symposium by highlighting how patient-, disease- and treatment-related factors all affect decisions made by physicians.
Professor Agnes Lee introduces the Bayer symposium on complex case scenarios in the treatment of VTE. VTE, venous thromboembolism
For the first presentation, Dr Marc Carrier discussed the case of Antonia, who developed a pulmonary embolism (PE) during pregnancy. Although this was resolved by treating with low molecular weight heparin (LMWH), a VTE recurrence following treatment cessation led to Dr Carrier discussing non-vitamin K oral anticoagulants (NOACs) as treatment options in both the acute and extended periods.
Dr Marc Carrier presents real-world evidence supporting the continuation of rivaroxaban in his patient. CI, confidence interval; HR, hazard ratio; NC, non-calculable; VTE, venous thromboembolism
Dr Ander Cohen continued the theme of extended anticoagulation by discussing issues related to the treatment of deep vein thrombosis (DVT) in a hypothetic patient case in which the patient develops multiple challenging comorbidities, including an arthritis flare, COVID-19 pneumonitis and declining renal function.
Dr Ander Cohen considers treatment options for a patient with DVT who develops COVID-19 pneumonitis. DVT, deep vein thrombosis; LMWH, low molecular weight heparin; NOAC, non-vitamin K oral anticoagulant; od, once daily; VKA, vitamin K antagonist
Finally, Dr Mari Thomas addressed the issue of patient preference by discussing a patient with CAT who was not adherent to LMWH due to a dislike of daily injections. Dr Thomas’s presentation concluded with a pre-recorded video of her interviewing Deborah, a patient who was involved in the COSIMO trial. The objective of COSIMO was to assess patient-reported treatment satisfaction, as measured by a primary outcome of Anti-Clot Treatment Scale (ACTS) Burdens score at 4 weeks, in patients who switched from standard-of-care treatment to rivaroxaban. Deborah provided a personal perspective on the challenge of daily injections and her preference for oral medication.
Dr Mari Thomas interviews Deborah about her experience in the COSIMO study. VTE, venous thromboembolism
The symposium concluded with a Q&A session. Audience questions included whether cancer patients who develop a clot following surgery should be considered at low or high risk of recurrence and whether thrombophilia should be screened for in patients with unprovoked PE.
The Bayer symposium panel field audience questions. ISTH, International Society on Thrombosis and Haematosis
Although IDDVT accounts for up to 56% of all DVTs, current guidelines only suggest anticoagulation for patients with IDDVT with severe symptoms or risk factors for extension. Anticoagulant treatment duration for isolated distal deep vein thrombosis (IDDVT) also tends to be shorter than for DVT. The Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis (RIDTS) trial aimed to assess the efficacy and safety of two different durations of rivaroxaban in patients with IDDVT. Patients with a first symptomatic IDDVT were treated with rivaroxaban 15 mg bid for 21 days followed by rivaroxaban 20 mg od for 21 days, for a total of 6 weeks, after which they were randomized to either placebo or rivaroxaban 20 mg od for a further 6 weeks. The composite primary efficacy outcome (recurrent IDDVT, and occurrence of proximal DVT and symptomatic fatal or non-fatal PE at 6 months) occurred less frequently in the rivaroxaban group compared with the placebo group (2.6% vs 9.8%; p=0.003). There were three (0.7%) major bleeding events prior to randomization but none after randomization. The authors therefore concluded that rivaroxaban is well-tolerated and effective for the reduction of recurrent VTE up to 3 months, compared with 6 weeks of treatment during a 6-month follow-up period.
Primary efficacy outcomes from the RIDTS trial. PE, pulmonary embolism; VTE, venous thromboembolism
CONKO-011 is an open-label trial investigating patient-reported treatment satisfaction with rivaroxaban compared with LMWH for the treatment of CAT. The first reported results from this study indicate that rivaroxaban reduced anticoagulant-related burden, as measured by the ACTS. Fewer patients requested cessation of rivaroxaban treatment (11.1%) compared with LMWH (19.4%) and rates of major bleeding events were similar between the treatment groups. Treatment satisfaction is increased with rivaroxaban compared with LMWH, which may improve patient adherence to therapy.
The ISTH has updated its guidance on the use of NOACs in obese patients. Previous guidance suggesting that NOACs should not been used in heavier patients has been amended to specify that rivaroxaban and apixaban are appropriate anticoagulation options, regardless of high body weight or BMI. This update is based upon available data showing that rivaroxaban and apixaban have at least similar efficacy and safety to vitamin K antagonists (VKAs), both individually and in pooled studies. Of note, a greater volume of data are available for rivaroxaban in obese patients than for apixaban in this population. The guidelines now also recommended that NOACs should not be used immediately following bariatric surgery, due to concerns regarding reduced absorption, but they are suitable for use in the sub-acute and chronic phases.
Comparative effectiveness of NOACs compared with VKAs in VTE4
An analysis of 12-month outcomes from the GARFIELD-VTE registry of patients with VTE showed reduced mortality following treatment with NOACs compared with VKAs (hazard ratio [HR]=0.58; 95% confidence interval [CI] 0.42–0.79). A higher proportion of patients receiving VKAs than those receiving NOACs died as a result of VTE complications (4.9% vs 2.2%) or fatal bleeding (4.9% vs 0.0%). Results were consistent in patients with active cancer and with renal insufficiency.
Patients receiving anticoagulation treatment and causes of death over 36 months5
The 36-month results from the GARFIELD-VTE registry (n=10,679) demonstrated that while 87.6% of patients were receiving anticoagulation at 3 months, this dropped to 54.2% at 12 months and 42.0% after 36 months. The most frequent cause of death during the 36 months of the analysis was cancer (n=565, 48.6%), followed by cardiac events (n=94, 8.1%) and VTE (n=38, 3.2%).
The GARFIELD-VTE mortality risk model6
Using data from the GARFIELD-VTE registry, a multivariable prediction risk model for 2-year mortality in patients with VTE has been developed. Predictors that were identified for all-cause mortality included creatinine, surgery and active cancer. The model has been externally validated using the Danish Nationwide Database and can therefore be used to guide clinical decision-making.
Predictors of mortality from the GARFIELD-VTE mortality risk score, presented by Dr Alfredo Farjat. CI, confidence interval; HR, hazard ratio; VTE, venous thromboembolism
The Vienna Prediction Model and identification of high-risk patients7
The Vienna Prediction Model (VPM) is a tool for estimating the risk of recurrence in patients with a first unprovoked DVT of the leg and/or PE. Of 264 patients identified as high risk by the VPM, 73 were not treated with anticoagulation, of whom 15 (21%) had a recurrent VTE event. In patients with an unprovoked DVT of the leg and/or PE that are at high risk of recurrence, as predicted by the VPM, anticoagulation therapy is effective at preventing recurrence. Conversely, the risk of recurrence remains high if patients are left untreated. The risk of bleeding during extended anticoagulation is low. The VPM may therefore be useful in the identification of patients at high risk for recurrence who would benefit from extended anticoagulation.
The VTE-PREDICT model: 5-year VTE recurrence and bleeding risk8
The newly developed VTE-PREDICT model aims to predict 5-year VTE recurrence and bleeding risk in patients who have completed ≥3 months of anticoagulant treatment. Initial analyses from the validation of this model in 15,283 patients identified multiple factors contributing to the risk of recurrent VTE or bleeding, of which age, female sex and history of cancer were identified as contributing factors for both outcomes. The VTE-PREDICT model could be used to predict the effect of extended anticoagulation for an individual patients and therefore aid in shared decision-making.
NOACs for the prevention of recurrent VTE9
A prospective cohort study in Italy enrolled 934 patients with acute VTE that were treated with NOACs to assess the efficacy and safety of the NOACs in both the acute and extended phases. Mean treatment duration was 21.6 months, and during this time seven recurrent VTE events and 25 major bleeding events occurred. Treatment was withdrawn in 290 patients and, during follow-up of these (mean duration 31.9 months) there were 22 recurrent VTE events and two episodes of major bleeding. In this study, NOACs demonstrated a favourable risk–benefit profile in the extended phase, following an acute VTE event.
Results from the TacDOAC registry were presented as both an oral presentation and a poster. In an analysis of 202 patients receiving concurrent anti-cancer therapy and NOACs, there were nine major bleeding events (cumulative incidence: 4%; 95% CI 2–8%) and 12 non-major bleeding events (cumulative incidence: 6%; 95% CI 3–10%). The cumulative incidence was of major bleeding events was highest in patients who received a Bruton’s tyrosine kinase inhibitor alongside a NOAC (10%), followed by those who received a vascular endothelial growth factor (VEGF) inhibitor (7%). VEGF inhibitors were also associated with an increased risk of VTE compared with other anti-cancer treatments, occurring in 2/28 (7.1%) of patients. Treatment with NOACs and some targeted cancer therapies is associated with a higher risk of bleeding events, and larger studies are therefore required to determine how best to care for these patients.
Professor Agnes Lee highlighted the current low quality of evidence supporting the management of recurrent VTE in patients with cancer. After discussing guideline recommendations, she presented her own suggested approach.
Suggested approach for the management of recurrent VTE in patients with cancer presented by Professor Agnes Lee. DOAC, direct oral anticoagulant; INR, international normalized ratio; LMWH, low molecular weight heparin; VKA, vitamin K antagonist; VTE, venous thromboembolism
Dr Casey O’Connell provided a ‘State-of-the-Art’ talk on the available options for the treatment of CAT. LMWH and NOACs were the primary options covered, with specific situations where the heparins might be preferable highlighted. She also noted that patient compliance with NOACs is significantly higher than with LMWH.
Professor Connie Hess presented in a State-of-the-Art session discussing the role of NOACs for the treatment of PAD. There is a paucity of data for the use of antithrombotic strategies in PAD, but data from the COMPASS and VOYAGER PAD studies indicate that rivaroxaban 2.5 mg bid plus low-dose aspirin is an effective treatment. This treatment regimen was effective regardless of prior clopidogrel use in VOYAGER PAD and reduced the risk of acute limb ischaemia when compared to placebo. Although there was a slight numerical increase in Thrombolysis In Myocardial Infarction (TIMI) major bleeding associated with the rivaroxaban treatment regimen compared with control, there were no increases in intracranial haemorrhage or fatal bleeding events. Professor Hess concluded by presenting a suggested clinical framework for the treatment of PAD
Clinical framework for the use of antithrombotic agents in PAD, presented by Professor Connie Hess. ACS, acute coronary syndrome; CAD, coronary artery disease; DAPT, dual antiplatelet therapy; MACE, major adverse cardiovascular event; MALE, major adverse limb event; PAD, peripheral artery disease; PCI, percutaneous coronary intervention
Analysis of results from the VOYAGER PAD study of rivaroxaban in patients with PAD requiring revascularization indicated that rivaroxaban 2.5 mg bid in combination with low-dose aspirin reduces the risk of venous and arterial thrombotic events compared with aspirin alone. Results were consistently favourable for rivaroxaban for both first (HR=0.76; 95% CI 0.67–0.87; p<0.0001) and total (HR=0.77; 95% CI 0.67–0.89; p=0.0005) thrombotic events. This equates to 4.8 first events and 6.1 total events prevented per 100 patients treated with rivaroxaban versus placebo.
Scott Berkowitz discusses the number of thrombotic events prevented by rivaroxaban in VOYAGER PAD. CI, confidence interval; HR, hazard ratio; ISTH, International Society on Thrombosis and Haematosis; PAD, peripheral artery disease; VTE, venous thromboembolism