ISTH congress highlights from Bayer July 2019

Congress overview

2019 marked a special year for the International Society on Thrombosis and Haemostasis (ISTH), being the 50^th anniversary of its founding and the first year of the new annual congress format in collaboration with the ISTH Scientific and Standardization Committee (SSC). This fully integrated event was held in Melbourne, Australia, and hosted more than 5000 global experts under the theme of ‘Research, Discovery, Outcomes’. There were more than 2100 submitted abstracts showcasing the latest research in thrombosis, haemostasis and vascular biology. The programme featured plenaries, education and poster sessions, as well as SSC subcommittee sessions and industry-sponsored events.

Topic streams at the ISTH 2019 Congress with artwork created by a local indigenous artist, Mick Harding

The ISTH 2019 Annual Congress at the Melbourne Convention and Exhibition Centre

Insights from the GARFIELD Registries

Data from the GARFIELD Registries were presented at a Thrombosis Research Institute (TRI) Satellite Symposium titled ‘Understanding the Outcomes of Anticoagulation: Insights from the GARFIELD Registries’ chaired by Rt Hon Professor the Lord Ajay K. Kakkar, Director of the TRI, UK. These data are discussed in sections throughout the newsletter.

More information on these registries can be found here:
https://www.tri-london.ac.uk/our-research/#two

Continued underuse of anticoagulants in atrial fibrillation

In the TRI Satellite Symposium, Professor Harry Gibbs (Sydney, Australia) presented evidence from the GARFIELD-AF Registry that demonstrated continued underuse of anticoagulation therapy in patients with atrial fibrillation (AF). Of 26,742 patients with newly diagnosed non-valvular AF and ≥1 risk factors for stroke enrolled in the registry, 28.4% did not receive anticoagulation therapy. Instead, 60% of these patients received antiplatelet therapy, an approach not recommended by guidelines and potentially harmful.1 There were significant mortality differences in favour of oral anticoagulants (versus non-use) and non-vitamin K antagonist oral anticoagulants (NOACs) (versus vitamin K antagonists [VKAs]). In a State-of-the-Art presentation on this unmet need, Professor Elaine M. Hylek (Boston MA, USA) suggested that the risk of bleeding with anticoagulation therapy is often overestimated and stressed the need to put this risk in context with the risk of stroke, which is associated with a 28-day mortality of ~20%.2

Adjusted 2-year survival of patients enrolled in the GARFIELD-AF Registry (patients with a CHA₂DS₂-VASc score of ≥2)

Anticoagulant use and clinical outcomes in patients with cancer-associated thrombosis (CAT)

As presented by Professor Jeffrey I Weitz (Ontario, Canada) during the TRI Satellite Symposium, of 10,685 patients with treated acute venous thromboembolism (VTE) enrolled in the GARFIELD-VTE Registry 9.9% had active cancer and 6.3% had a history of cancer. Among patients with active cancer receiving a NOAC, the 12-month unadjusted event rate of recurrent VTE was 4.4%. This is in line with data from the select-d and Hokusai-VTE-Cancer studies.3,4

It was interesting to note that among patients with active cancer, the use of parenteral-only therapy decreased over time from ~58% at 30-days post-enrolment to 26% at Month 12 post-enrolment. NOAC use in the active cancer cohort remained consistent at ~25% throughout 12-months of follow-up. These patterns might be explained by differences in mortality between the treatment cohorts, which was higher in patients who received parenteral-only therapy (54.3%) than in patients prescribed a NOAC (30.9%). This suggests that parenteral treatment was preferentially used in the sickest of cancer patients. Low persistence with low molecular weight heparins (LMWHs) might also explain why LMWH use has decreased over time; this would be likely attributable to the burden of daily subcutaneous injections and the high costs of therapy.3,4 Persistence with anticoagulant therapy is crucial for protection against the long-term risk of recurrent VTE, which is 3-times higher in patients with active cancer than in those without.5

Anticoagulant treatment in patients in the GARFIELD-VTE Registry according to cancer status

Tailoring anticoagulation therapy for CAT

It has been just over a year since the publication of results from the select-d and Hokusai-VTE-Cancer studies,3,4 and subsequently published guidance, including from the ISTH SSC, that endorses rivaroxaban and edoxaban use in patients with active cancer.6 Professor Marc Carrier (Ottawa, Canada), Vice President of the ISTH SSC, remarked that

“CAT treatment is an evolution and with more anticoagulants in our toolbox we can better tailor therapy” but stressed that “we need to think through our choices carefully”.

In a State-of-the-Art Session presentation by Professor Agnes Lee (Vancouver, Canada), the audience was reminded of the reduced risk of recurrent VTE and the increased risk of major bleeding with NOAC compared with LMWH use in patients with cancer.7 Data from select-d and the Hokusai-VTE-Cancer studies were used to highlight that the higher risk of bleeding with NOACs is driven by the presence of gastrointestinal malignancy and additional risk factors for bleeding. The key take-away from this presentation was that

“The benefit–risk profile of CAT treatment will improve if we consider the right drug for the right patient at the right time”.

Professor Carrier illustrated how this might be achieved in a Joint SSC session on the topic. In presenting an algorithm developed by a Canadian Expert Consensus,8 there was the suggestion to

“apply caution, consider the baseline characteristics of a patient and re-assess on a regular basis”.

A 4-step risk adapted appraoch in evaluating anticoagulant choice in patients with CAT

The Bayer-sponsored symposium

The premise of ‘the right drug for the right patient at the right time’ was the focus of the Bayer-sponsored satellite symposium ‘Anticoagulation in Active Cancer Patients: How NOACs Changed Clinical Practice’. Professor Peter Verhamme’s (Leuven, Belgium) case study presentation prompted some important discussions between the audience and panel including appropriate anticoagulant drug and dose selection in cancer-specific challenging clinical scenarios. During these discussions, Professor Alok Khorana (Cleveland OH, USA) highlighted data which demonstrates that case fatality rates are higher with recurrent VTE than with bleeding.9

The Bayer-sponsored satellite symposium ‘Anticoagulation in Active Cancer Patients: How NOACs Changed Clinical Practice’

New Guidance for anticoagulation for cancer patients with non-valvular AF

In an oral abstract session, Professor Cihan Ay (Vienna, Austria) presented results from a nationwide study on the prevalence and risk of AF in patients with cancer in Austria. The relative risk of AF was shown to be 10-fold higher in patients with cancer compared with those without cancer. Although LMWH is used for the treatment of CAT, there is no evidence of its efficacy for the prevention of stroke in patients with AF, for which the NOACs apixaban, dabigatran, edoxaban and rivaroxaban and VKAs are indicated (OC 41.5).

In addressing this issue, the SSC Hemostasis and Malignancy subcommittee presented on new guidance for the anticoagulation of cancer patients with non-valvular AF receiving chemotherapy, which are now published in the Journal of Thrombosis and Haemostasis (https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.14478).

The prevalence of AF in patients with cancer is lower than in patients without (OC 41.5).

How useful is dichotomizing VTE as provoked or unprovoked?

In a presentation by Professor Philip Wells (Ottawa, Canada) during the Bayer Product Theatre, new evidence suggested that duration of VTE treatment according to the provoked or unprovoked nature of the index event can underestimate the risk in some patients. The risk of recurrence with VTE provoked by major risk factors such as surgery is very low (<1.0% per year) warranting a guideline-recommended duration of therapy of 3 months.10,11 With unprovoked VTE the recurrence risk is very high at ~10% in the first year warranting extended anticoagulation therapy.11 But provoked VTE can be further defined considering minor risk factors such as inflammatory bowel disease and pregnancy. In a pooled analysis of EINSTEIN CHOICE and EINSTEIN EXT, recurrence rates associated with these factors were not significantly lower than with unprovoked VTE.12 Professor Wells concluded that extended treatment might benefit some patients with provoked VTE and that minor risk factors for VTE recurrence need to be individually assessed.

VTE provoked by minor risk factors has a similar risk of VTE recurrence compared with unprovoked VTE12

The Bayer-sponsored Product Theatre

Managing multi-morbidities in non-valvular AF

A key theme regarding thrombosis management at this year’s ISTH congress was the management of challenging patient groups, such as those with co-morbidities. One-in-four patients with non-valvular AF have diabetes, which can cause a progressive decline in kidney function. In an oral abstract presentation, Professor Craig Coleman (Connecticut CT, USA) showcased results from a retrospective analysis of US claims data. Compared with warfarin, rivaroxaban was associated with a 17% lower risk of acute kidney injury and an 18% lower risk of progression to stage 5 chronic kidney disease or haemodialysis (OC 21.2). Patients with type 2 diabetes are also at an increased risk of peripheral artery disease and related adverse events. Professor William Baker (Connecticut CT, USA) shared results from a retrospective claims database analysis of patients with these co-existing conditions. Rivaroxaban use was associated with a lower risk of both major adverse cardiovascular and limb events with no observed differences in major bleeding in patients with non-valvular AF and type 2 diabetes (OC 21.3).

Further information

The ISTH 2020 Congress will be taking place in Milan, Italy from 11−15 July. For more information on this event, visit: https://www.isth.org/page/isth2020

To keep up to date on venous and arterial protection, visit:
https://www.thrombosisadviser.com

References

Kirchhof P et al. Eur Heart J 2016;37:2893–2962. Return to content
Kaarisalo MM et al. Stroke 1997;28:311–315. Return to content
Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral Factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018;36(20):2017–23. Return to content
Raskob GE et al. N Engl J Med 2018;378:615–624. Return to content
Prandoni P et al. Blood 2002;100:3484–3488. Return to content
Khorana AA et al. J Thromb Haemost 2018;16:1891–1894. Return to content
Li A et al. Thromb Res 2019;173:158-163. Return to content
Carrier M et al. Current oncology (Toronto, Ont) 2018;25:329–337. Return to content
Abdulla A et al. Blood 2018;132:2528. Return to content
Iorio A et al. Arch Intern Med 2010;170:1710–1716. Return to content
Rodger MA et al. BMJ 2017;356:j1065. Return to content
Prins MH et al. Blood advances 2018;2:788–796. Return to content

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ISTH congress highlights from Bayer July 2019