In the midst of everything that is going on with COVID-19 it is easy to see how important non coronavirus stuff can get overlooked. But we still need to keep our eyes open. After a 3 year process involving many meetings, stakeholder comments, high levels of oversight and fantastic technical support, the National Institute of Health and Care Excellence in the UK (NICE) released their updated guidelines on the diagnosis and management of venous thromboembolic (VTE) disease1. Given the current situation, it has not had much press. However, we need this type of guidance more than ever at present, to support ambulatory pathways, refined diagnostic testing and bespoke therapeutic intervention. It’s a lengthy but very useful document and as always at St Emlyns, we would suggest you read the whole thing rather than take our word on the big changes. I know that many of you will be anxious to know how this guidance and clotology in general all relates to the current pandemic – don’t worry, that’s coming in a Part 2 very soon. But now, to the NICE guidance:
What are the big new changes?
Firstly for emergency medicine, this guideline now officially supports the use of age adjusted d-dimer strategies for both DVT/PE and the use of the Pulmonary Embolism Rule Out Criteria (PERC). The guidance also supports the use of quantitative point of care d-dimer assays, which may help smaller departments with limited access to imaging/lab testing and could be helpful in primary care. These are big steps forwards, that will hopefully reduce the use of invasive imaging and the use of therapeutic anticoagulation pending imaging. Caveats are highlighted and these tools are not for indiscriminate use. Read the detail and ensure you are happy with your pretest probability and your local assays before you adopt them.
This guideline also now supports the use of DOACs as interim anticoagulation pending diagnosis. No more 4 nights of awkward prescriptions and a district nurse administering LMWH at home, if you (or more importantly the person you are treating) don’t want to. Just a starter pack of DOAC therapy and people can be on their way with some pills. Again, this is not for everyone – if your scan is arranged for the next day then often a single shot of LMWH in the department will be more reliable than a prescription of BD tablet therapy. However, it is a nationally endorsed option now, which is helpful.
There is support for outpatient management of both suspected and confirmed PE, in line with recent work from the British Thoracic Society2. I suspect many of you are already doing this. Good to know that NICE supports the process though, and there is clear description of the relevant key issues, such as using a validated score to identify which patients are suitable for ambulatory care, and the importance of early follow up to ensure compliance and improving symptoms. Are you doing all this? You should be.
A long and complex cost effectiveness analysis and lots of expert discussion has led to 2 emerging winners in the DOAC wars. Rivaroxaban and apixaban were deemed to be the best options for interim and continuing anticoagulation, based on their cost effectiveness, clinical effectiveness and lack of requirement for LMWH lead in therapy. Further head to head trials are ongoing3 and maybe we will see an overall winner in the future? In the meantime, this narrowing of focus is helpful. In addition, there is guidance on when to think about other therapies in specific populations and how to administer them, such as patients with a high BMI, renal failure, antiphospholipid syndrome or active cancer.
Speaking of cancer, this guidance takes two bold steps into the future. There is support for DOAC use as first line therapy in cancer associated VTE, taking into account tumour site, bleeding risk and drug interactions (including therapeutic agents). This is potentially of huge benefit if the clinical effectiveness is comparable. Recent high quality RCT data4, published subsequent to the NICE evidence review, suggests that it is and supports these recommendations. Who wants to take subcutaneous injections for 6 months? Not me. In addition, there is some backpedalling on the earlier recommendation regarding screening CT abdo and pelvic scans for occult cancer in unprovoked VTE. Recent evidence suggests this adds little benefit5 to a directed history, physical examination, routine work up and gender specific testing. As such, the recommendations in this guideline are not to proceed to CT imaging unless there is specific concern regarding malignancy.
Lastly, there has been some work on when to stop anticoagulation, including a thorough evidence review of all currently available prediction tools for recurrence. The headline, unfortunately, is that none of these tools are great. Patients should be reviewed at 3 months following the diagnosis of VTE and a sensible individualised discussion had, taking into account provocation, risk of recurrence, bleeding risk and tolerance of therapy to date.
What has not changed?
No magic solutions or updated recommendations on the following issues, which were all considered to be out of scope – isolated distal DVT, isolated subsegmental PE, superficial venous thrombosis, massive PE, submassive PE (intermediate risk with raised biomarkers but no haemodynamic instability) and reduced dose thrombolysis. Also, the evidence on clinical probability adjusted d-dimers came6 through too late for inclusion in the review. At least you can do some further St Emlyns reading on all these7…..
How will these recommendations help?
These recommendations provide some assurance to those already using PERC and age adjusted D-Dimer and outpatient management strategies that they are practicing evidence-based medicine. In addition, they will also gently nudge those not using these strategies towards them. A variety of stipulations in the NHS contract mandate practice to be in line with NICE guidance; this contract can now act as a valuable trigger for change, if you have previously met local resistance while trying to implement any of the above. Finally, these guidelines offer some clarity around the safety and broad clinical application of DOAC agents in VTE. Long live the tablet, down with the needle. There are research recommendations in the detail as well and anyone looking to get funding on VTE research would be sensible to look at these.
Take a look, let us know what you think and if this wasn’t COVID enough for you – don’t forget my previous post8 from a few weeks ago….
- 1.NICE N. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. NICE. https://www.nice.org.uk/guidance/NG158. Published 2020. Accessed 2020.
- 2.Howard LSGE, Barden S, Condliffe R, et al. British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism (PE). Thorax. June 2018:ii1-ii29. doi:10.1136/thoraxjnl-2018-211539
- 3.Clinical T. Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism (COBRRA). Clinical Trials. https://clinicaltrials.gov/ct2/show/NCT03266783. Published 2019. Accessed 2020.
- 4.Agnelli G, Becattini C, Meyer G, et al. Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer. N Engl J Med. March 2020. doi:10.1056/nejmoa1915103
- 5.Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med. August 2015:697-704. doi:10.1056/nejmoa1506623
- 6.Kearon C, de Wit K, Parpia S, et al. Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability. N Engl J Med. November 2019:2125-2134. doi:10.1056/nejmoa1909159
- 7.Horner D. Level Pegging and the PEGED study. St Emlyn’s. https://www.stemlynsblog.org/level-pegging-jc-and-the-peged-study-stemlyns/. Published 2019. Accessed 2020.
- 8.Horner D. Covid 19 and clotting diagnosis, d-dimers and dilemmas. St Emlyn’s. https://www.stemlynsblog.org/covid-19-and-clotting-diagnosis-d-dimers-and-dilemmas/. Published 2020. Accessed 2020.