Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism

Reasons for the decision

A new trial [GAPS trial (Shalhoub et al. 2020)] compared a combination of low molecular weight heparin (LMWH) plus anti-embolism stockings (AES) versus LMWH alone and found LMWH alone to be non-inferior in venous thromboembolism (VTE) reduction at 90 days post-surgery. This trial recruited non-orthopaedic, elective surgery patients. Patients with some of the highest risk factors for VTE (such as a history of VTE or thrombophilia); or with certain features in the procedure or history requiring them to have extended prophylaxis were excluded. This trial did not stratify or conduct subgroup analyses based on different types of surgical procedures.

The trial's findings do not affect the current recommendations. The guideline recommends considering either a pharmacological prophylaxis or a mechanical prophylaxis as an alternative if there are bleeding risks for the surgical procedure. The option of using both a mechanical and pharmacological prophylaxis, rather than only 1 type of prophylaxis is limited to certain circumstances.

For patients undergoing bariatric or other procedures in the abdominal area, the recommendation was to start a mechanical prophylaxis on admission. If an individual patient has VTE risks which outweigh the risk of bleeding, a pharmacological option such as LMWH should be offered as an additional prophylaxis method. A similar approach is recommended for procedures where the risk of bleeding is important (cranial, spinal, thoracic, or cardiac surgery), except that the recommendation is to consider rather than offer these options. The choice of wording used reflected the strength of the evidence base supporting the recommendations and emphasised balancing the risks of VTE and bleeding in individual patients.

As the NICE guideline limits the use of combination prophylaxis to specific circumstances, it will not be necessary to update it. The new evidence does not provide evidence to support the replacement of mechanical prophylaxis with pharmacological prophylaxis as single therapy.

Overview of 2023 surveillance methods

NICE's surveillance team checked whether recommendations in NICE's guideline on venous thromboembolism in over 16s remain up to date.

The surveillance process consisted of:

For further details about the process and the possible update decisions that are available, see ensuring that published guidelines are current and accurate in developing NICE guidelines: the manual.

Evidence considered in surveillance

Focused literature search

Ongoing research

We checked for relevant ongoing research. Of the ongoing studies identified, we found 1 RCT on AES versus no AES in surgical patients with low thrombosis risk, and 1 protocol for a systematic review of the baseline risk of VTE and major bleeding in patients with general and gynaecologic surgery. These have the potential to affect recommendations. The publication of the results of these studies will be monitored. Once results are available, the impact on current recommendations will be evaluated as quickly as possible. These studies are:

In addition to the studies on the prophylaxis strategy, we also followed up on the status of the recommendation for research in the NICE guideline on what is the accuracy of individual risk assessment tools in predicting the risk of VTE and risk of bleeding in people admitted to hospital. There is a major study funded by NIHR, and the initial results were published in the BMJ in 2021 (Horner et al. 2021). The review concluded that it is uncertain which risk assessment model (RAM) is optimal for assessing the risk of VTE and variation exists in their composition of risk factors and thresholds for high and low risk. The full NIHR report is yet to be published.

Intelligence gathered during surveillance

Information considered when developing the guideline

The evidence review on risk assessment was unable to identify a risk assessment tool or model that can accurately predict the risks of VTE and bleeding. Therefore, the guideline did not specify which tool should be used or the choice of prophylaxis on the risk scores. Instead, the risk assessment approach emphasised balancing VTE risks against adverse effects of prophylaxis. Clinicians have a choice of using the Department of Health VTE risk assessment tool (2010), or other validated risk assessment tools.

Recognising that the type of surgery received is an important factor affecting the risk of VTE, clinical health economics data were analysed and interpreted based on the type of surgery received by study participants. Unlike earlier versions of VTE prophylaxis guidelines, extrapolation of evidence from one surgical population to another was minimal. This change in evidence interpretation approach led to a change in recommendations; the current guideline recommends considering using either a pharmacological prophylaxis (or a mechanical prophylaxis if there are bleeding risks) for most types of non-cancer and non-orthopaedic elective surgical procedures. The choice of recommendation wording (offer versus consider) reflects the certainty of the evidence base supporting the recommendation and whether it applies to every patient or only to patients with certain risk profiles.

For the non-orthopaedic, elective surgery population, the largest body of evidence was in abdominal surgery. There was data from 67 RCTs, and 11 of these RCTs were published after the year 2000. A network meta-analysis (NMA) was conducted for the outcomes DVT, PE and major bleeding to identify the most effective VTE prophylaxis strategy. 48 RCTs were included in the NMA for the outcomes of DVT, 26 for PE and 24 for major bleeding. The NMA showed that combination prophylaxis strategies using both pharmacological and mechanical interventions were more clinically beneficial for reducing DVT compared to pharmacological or mechanical interventions as standalone interventions. LMWH initiated post-operatively in combination with IPCD was ranked as the most clinically effective prophylaxis in the NMA for DVT.

Therefore, the recommendations are to offer a mechanical prophylaxis option, and if the VTE risks outweigh the bleeding risks in an individual patient, another pharmacological prophylaxis should be offered in addition to the mechanical prophylaxis. The same recommendations were made for bariatric surgery, based on the extrapolation of evidence from the abdominal surgery group (due to the site of the surgery), and the concerns that this group of patients are often at an increased risk of VTE due to obesity.

As there was less data for surgery, thoracic surgery and cardiac surgery and there are some similarities, data from abdominal surgery was considered as indirect evidence. For these surgical procedures, the recommendations were to consider a mechanical prophylaxis if the patient has an increased risk of VTE and if the VTE risks outweigh the risk of bleeding in an individual patient, consider adding a LMWH (or fondaparinux if LMWH is contradicted). Similar recommendations were also made for certain surgical procedures where bleeding is an important risk (such as intra-cranial and spinal surgery), and an addition of LMWH to AES may provide additional VTE prevention.

Equalities

No equalities issues were identified during the surveillance process.

Stakeholder consultation

We received consultation responses from 8 stakeholders, which included 4 professional organisations, 1 patient organisation, 1 hospital trust and 2 commercial companies.

See appendix A for stakeholder consultation comments and our responses.

Of the stakeholders, 2 agreed with our proposal to not update the guideline based on the GAPS trial. Of the 6 stakeholders who thought the guideline should be updated, 3 provided suggestions that are out of scope of this surveillance review. These suggestions included considering a new trial on aspirin in orthopaedic surgery patients (this study is being assessed by NICE), and concerns about clarity or the wording of the recommendations, implementation challenges, and other areas of the guideline such as risk assessment and prophylaxis in gynaecology.

Of the stakeholders who thought that the guideline should be updated based on the trial, 1 suggested that the study is hard evidence showing that AES have no clinical benefit, and strongly urged the committee to reconsider their evidence on mechanical thromboprophylaxis, to reflect that the benefits of IPC are clear but that there is no evidence to support AES. The other stakeholder who disagreed with the proposal not to update the guideline suggested that clarity is needed around the use of AES, as clinicians find the recommendations around AES unhelpful as the advice differs for different specialities. This stakeholder was also concerned that since the publication of the trial, many centres have stopped stockings usage in medical and obstetrics specialities and some have also stopped in surgery as the evidence for stockings is mostly very old, and the trial did support the use of stockings in surgical specialities included in the study. One stakeholder suggested that there is very little evidence to support their use generally and stronger statements would facilitate withdrawal of use (with consequent cost savings). However, these concerns are more suggestive of misinterpretation and implementation issues of the current NICE guidelines and misinterpretation of the impact of the GAPS trial.

All three stakeholders also referred to the implementation issues, such as those found in the NHS GIRFT-Thrombosis report from 2021, which suggested that inadequate funding for a VTE prevention team (only 22% of surveyed trusts have 1), and variations in prophylaxis methods used.

There were no equality issues specific to the prophylactic choices in non-orthopaedic elective surgery patients. One stakeholder noted the concern of inadequate funding for a VTE prevention team found in the GRIFT report, while another suggested that the alternatives to people who refuse heparins (due to porcine origin) should be stated in the guideline.

See ensuring that published guidelines are current and accurate in developing NICE guidelines: the manual for more details on our consultation processes.

Overall decision

After considering the evidence, stakeholder feedback, intelligence and the impact on current recommendations, we decided that it would not be appropriate to recommend updating the guideline based on this study alone. Instead, we will be monitoring this area for more studies especially those related to surgical procedures in the abdominal area, the risk of VTE in current NHS practice, and VTE risk assessment/stratification.

In the absence of accurate risk stratification tools, extrapolating the overall findings of this study to the specific groups of elective surgery patients is difficult as risks may differ based on the type of procedure. Furthermore, the suggestions that the risk of VTE in surgical patients is now low in the NHS (and therefore, combination prophylaxis is not needed) were based mainly on non-UK based, orthopaedic surgery data only. The variation of interpretations and actions taken to implement the findings of this trial by topic experts and trusts probably reflects the challenges of interpreting this study and this is confirmed by the feedback received from some of the stakeholders during the consultation.

It is concerning that several stakeholders and topic experts had expressed the opinion that the GAPS trial showed that AES is not effective and should be withdrawn. It is important to emphasise this trial should not be taken as evidence that AES is ineffective, and the 1.5% incidence of VTE events observed as evidence that the risk of VTE is low in current NHS practice. The 1.5% incidence of VTE events was observed in a population that had excluded people who are most at risk of VTE and had more than 80% full compliance (for example, received all prescribed LMWH doses) of a pharmacological agent known to be effective. As the trial evaluated the effects of adding AES to LMWH; it should not be interpreted as evidence that AES is not effective when used on its own. The trial results suggested that adding AES to patients who are on LMWH probably offer no additional benefit for most elective surgery patients (without specific risk factors which put them at high risk of VTE).

In conclusion, despite the topic experts and the general impression from some stakeholders that the GAPS trial findings would necessitate the update of the NICE guideline, we do not think it does. The current guideline does not recommend combination prophylaxis for most of non-orthopaedic, elective surgery procedures; it recommends considering 1 type of prophylaxis (either a pharmacological option such as LMWH, or a mechanical option, such as AES) and the choice depends on the bleeding risks associated with the type of procedure, and individual risk factor. Combination prophylaxis is recommended or considered only in situations where the individual's increased risk of VTE still outweigh the risk of bleeding from the use of pharmacological prophylaxis despite the use of a mechanical prophylaxis. Therefore, a guideline update is not proposed at this point.

ISBN: 978-1-4731-4951-9